curcumin and Memory-Disorders

Memory impairment (MI) is one of the most common complaints of people referred to physicians for proper diagnosis. In addition, the prevalence of neurodegenerative lesions like Alzheimer is generally on the increase. Thus far, numerous laboratory studies have been conducted to evaluate the effect of curcumin on the improvement of MI.. The aim of this study was to review the efficacy of curcumin on MI in animal studies.. Keywords related to memory and curcumin were searched in PubMed, Web of Science, and Scopus databases based on MeSH; and articles published until July 2017 were later extracted. Then the articles (full text or abstract) were examined based on the inclusion and exclusion criteria. The present study evaluated articles that did not include specific pathologies such as Alzheimer.. A total of 90 articles met the inclusion criteria but only 25 articles underwent final review. The minimum and maximum dosages of curcumin were 5 and 480  mg/kg respectively. Curcumin was administered over the period of 1-84 days. The results of 24 articles showed that curcumin moderates short-term and long-term MI in various laboratory models such as aging, acute and chronic stress, anxiety, smoking, benzodiazepine and anticonvulsant consumption, and other conditions associated with increased oxidative stress.. The findings of this study revealed that curcumin moderated or reversed MI in rodents and did not have a placebo effect. Accordingly, curcumin can play a preventive and therapeutic role in MI.

Topics: Aging; Animals; Curcumin; Memory Disorders; Mice; Oxidative Stress; Rats; Stress, Psychological

It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments.

Topics: Brain-Derived Neurotrophic Factor; Carbohydrates; Cognition; Cognition Disorders; Curcumin; Diet, High-Fat; Dietary Supplements; Fatty Acids, Omega-3; Hippocampus; Humans; Memory; Memory Disorders; Obesity

Kalyanaka ghrita (KG) is an Ayurvedic formulation traditionally used in the treatment of Daurbalya (debility) and Smritidaurbalya (impairment of intellectual activities). Clinical studies have reported the effect of KG in the treatment of Manasmandata or Buddhimandyata which is associated with impaired learning, social adjustment and maturation.. The present study aims to standardization of KG and validation of its use in experimental models of neurodegeneration.. KG was Standardized for biomarkers curcumin, gallic acid, tannic acid, chebulagic acid, and berberine. In male wistar rats, neurodegeneration was induced by administration of intracerebroventricular Amyloid β (Aβ. A novel HPLC method has been developed for the standardization of KG. Treatment with KG significantly improved cognition and memory and increased brain BDNF and antioxidant status in Aβ. The findings suggest that KG has neuroprotective potential and along with its nootropic property could be a promising therapy for neurodegenerative diseases like Alzheimer's disease.

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Berberine; Brain-Derived Neurotrophic Factor; Curcumin; Cytokines; Disease Models, Animal; Male; Maze Learning; Memory Disorders; Neuroprotective Agents; Nootropic Agents; Rats; Rats, Wistar; Tannins

Neuroinflammation is a key pathological event triggering neurodegenerative process, resulting in neurologic sequelae. Curcumin (cur) has recently received increasing attention due to its anti-inflammatory properties. Therefore, we investigated the protective effects of curcumin on lipopolysaccharide (LPS)-induced memory impairments, long-term potentiation (LTP) deficits, hippocampal inflammatory cytokines, and neuronal loss in male rats. Rats were randomly divided into four groups as follows: (1) Vehicle; (2) cur; (3) LPS; and (4) cur/LPS. Following curcumin pretreatment (50 mg/kg, per oral via gavage, 14 consecutive days), animals received a single dose of LPS (1 mg/kg, intraperitoneally) or saline. Twenty-four hours after LPS/or saline administration, passive avoidance test (PAT), hippocampal LTP, inflammatory cytokines (TNFα, IL-1β), and neuronal loss were assessed in hippocampal tissue of rats. Our results indicated that pretreatment with curcumin in LPS-challenged rats attenuates memory impairment in PAT, which was accompanied by significant increase in the field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude. Hence, pretreatment with curcumin in LPS-treated rats decreased hippocampal concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β), as well as reduced neuronal loss in the hippocampal tissue. This study provide evidence that pretreatment with curcumin attenuates LPS-induced memory impairment and LTP deficiency, which may be partly related to the amelioration of inflammatory cytokines and neuronal loss in the hippocampal tissue.

Topics: Animals; Curcumin; Cytokines; Hippocampus; Lipopolysaccharides; Long-Term Potentiation; Male; Memory Disorders; Rats; Tumor Necrosis Factor-alpha

Previously, we observed curcumin improves aging-associated memory impairment in D-galactose (D-gal) and normal-aged (NA) mice. Evidence showed that multiple agents can be used in managing aging-induced memory dysfunction, drawn by the contribution of several pathways. Curcumin and Epigallocatechin 3 gallate (EGCG) combination substantially reduced the oxidative stress that commonly mediates aging. This study examined the combined effect of EGCG and curcumin on memory improvement in two recognized models, D-gal and normal-aged (NA) mice. The co-administration of EGCG and curcumin significantly (p < 0.05) increased retention time detected by passive avoidance (PA) and freezing response determined in contextual fear conditioning (CFC) compared to the discrete administration of EGCG or curcumin. Biochemical studies revealed that the combination of EGCG and curcumin remarkably ameliorated the levels (p < 0.05) of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation compared to the monotherapy of EGCG or curcumin in mice hippocampi. The behavioral and biochemical studies revealed that the combination of EGCG and curcumin showed better improvement in rescuing aging-associated memory disorders in mice. EGCG and curcumin combination could serve as a better choice in managing aging-related memory disorders.

Topics: Aging; Animals; Catechin; Curcumin; Galactose; Memory Disorders; Mice; Oxidative Stress

The aim of this study was to determine the protective effects of curcumin on memory, hippocampal acetylcholine level and apoptosis in a rat model of repeated cerebral ischemia. Male Wistar rats were divided into sham rats that received saline and the other 3 groups underwent 4-vessel occlusion brain ischemia (4VOI), received oral administration of either saline or curcumin at doses rate of 25mg/kg/day and 50mg/kg/day for 7 days. Memory function was evaluated by eight-arm radial maze task and Morris water maze (MWM) test, Acetylcholine release (ACh) in the dorsal hippocampus was evaluated by microdialysis-HPLC) and neuron apoptosis was investigated by terminal deoxynucleotidyltransferase mediated fluorescein-deoxyuridine triphosphate nick-end labeling. 4VOI test reviled impaired memory, reduced dorsal hippocampus Ach level and induced apoptosis in the Repeated Cerebral Ischemia rat model. Curcumin significantly improved the memory deficit (p<0.001), increased Ach level (p<0.001) and prevented hippocampal neuron apoptosis (p<0.001). Curcumin may be suggested as a promising therapy for ischemic cerebrovascular dementia and its beneficial effect is due to its memory preserving, ACh-increasing and neuroprotective effects in the rat.

Topics: Acetylcholine; Animals; Brain Ischemia; Cerebral Infarction; Curcumin; Hippocampus; Male; Maze Learning; Memory Disorders; Rats; Rats, Wistar

Bisphenol A (BPA) is an endocrine-disrupting chemical commonly utilized in the manufacture of plastics, which may cause damage to brain tissue. Curcumin is a phytochemical with protective effects against neurological and mental diseases. The purpose of this research was to evaluate whether nanomicellar curcumin (NmCur) might protect rats against BPA-induced learning and memory deficits. After determining the proper dose of BPA, the animals were randomly divided into 8 groups (8 rats in each group) receiving dextrose 5% (as vehicle of NmCur) (Dex), sesame oil (as vehicle of BPA) (Sea), Sea plus Dex, NmCur (50 mg/kg), BPA (50 mg/kg), and 50 mg/kg BPA plus 10, 25, and 50 mg/kg NmCur groups, respectively. Behavioral tests performed using passive avoidance training (PAT), open-field (OF), and Morris water maze (MWM) tests. The expression of oxidative stress markers, proinflammatory cytokines, oxidative stress-scavenging enzymes, glutamate receptors, and MAPK and memory-related proteins was measured in rat hippocampus and cortical tissues. BPA up-regulated ROS, MDA, TNF-α, IL-6, IL-1β, SOD, GST, p-P38, and p-JNK levels; however, it down-regulated GSH, GPx, GR, CAT, p-AKT, p-ERK1/2, p-NR1, p-NR2A, p-NR2B, p-GluA1, p-CREB, and BDNF levels. BPA decreased step-through latency (STL) and peripheral and total, but not central, locomotor activity. It increased the time to find the hidden platform, the mean of escape latency time, and the traveled distance in the target quadrant, but decreased the time spent in the target quadrant. The combination of BPA (50 mg/kg) and NmCur (25 and 50 mg/kg) reversed all of BPA's adverse effects. Therefore, NmCur exhibited neuroprotective effects against subacute BPA-caused learning and memory impairment.

Topics: Animals; Curcumin; Hippocampus; Learning; Male; Maze Learning; Memory; Memory Disorders; Neuroprotective Agents; Oxidative Stress; Rats

Restraint stress indicated induction of morphology, biochemistry, and behavioral impairments. Several investigations have reported that curcumin has a protective effect against stress disturbance. The present study is designed to investigate the effects of curcumin on learning and memory, activity, biochemical, morphology changes, and apoptosis in the hippocampus and prefrontal cortex of restraint stress rats. For chronic restraint stress, the rats were kept in the restrainers for 2.5 h per day for 21 consecutive days. The animals received the gavage of curcumin every other day for 21 days. After stress, the animals were subjected to behavioral tests. In restraint stress rats, locomotor activity and step-through latency were decreased using open field and shuttle box, respectively. Then, the rats were sacrificed to assess their serum and brains. A reduction was seen in the serum malonedialdehyde levels and number of neurons in the hippocampus and prefrontal cortex. The significantly decreased serum total antioxidant capacity levels and increased apoptotic cells were observed in the hippocampus and prefrontal cortex. Finally, curcumin inhibited and reversed the changes of stress induced in the prefrontal cortex and hippocampus of the rats. These findings provided evidence for the protective effect of curcumin therapy on biochemical, morphology, and behavioral changes induced by restraint stress. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Topics: Animals; Apoptosis; Curcumin; Hippocampus; Memory Disorders; Prefrontal Cortex; Rats; Restraint, Physical; Stress, Psychological

Noise pollution is one of the fundamental factors in the etiology of many disorders. Noise stress adversely affects cognitive behaviors and long-term potentiation (LTP), the candidate mechanism of learning and memory. In the present study, we examined the neuroprotective effects of nano-curcumin on behavioral and electrophysiological aspects of hippocampus-dependent memory in noise-exposed animals.. The stressed animals received either vehicle (ST) or nano-curcumin (NANO + ST) for 2 weeks. The control groups remained either intact (CON) or received nano-curcumin (NANO + CON). The ST and NANO + ST groups were exposed to daily noise for 2 weeks. The spatial memory was assessed in the Morris water maze. The LTP was investigated through field potential recording in the CA3-CA1 pathway of the hippocampus. Serum corticosterone level was measured at the end of the experiments.. The ST group showed a lower cognitive function and suppressed LTP compared to the CON group. The nano-curcumin treatment improved the maze navigation and LTP induction compared to the ST group. While the stress exposure elevated the serum level of corticosterone in the ST animals, nano-curcumin treatment reduced it.. The nano-curcumin treatment restores impaired behavioral and electrophysiological aspects of learning and memory in the noise-exposed animals. The plasma corticosterone levels may be associated with changes in cognitive behavior and synaptic plasticity.

Topics: Animals; Corticosterone; Curcumin; Hippocampus; Long-Term Potentiation; Maze Learning; Memory Disorders; Noise; Spatial Memory

Aging-induced memory impairment is closely associated with oxidative stress. D-Galactose (D-gal) evokes severe oxidative stress and mimics normal aging in animals. Curcumin, a natural flavonoid, has potent antioxidant and anti-aging properties. There are several proteins like glutathione S-transferase A1 (GSTA1), glutathione S-transferase omega-1 (GSTO1), kelch-like ECH-associated protein 1 (KEAP1), beta-secretase 1 (BACE1), and amine oxidase [flavin-containing] A (MAOA) are commonly involved in oxidative stress and aging. This study aimed to investigate the interaction of curcumin to these proteins and their subsequent effect on aging-associated memory impairment in two robust animal models: D-Gal and normal aged (NA) mice. The aging mice model was developed by administering D-gal intraperitoneally (i.p). Mice (n = 64) were divided into the eight groups (8 mice in each group): Vehicle, Curcumin-Control, D-gal (100mg/kg; i.p), Curcumin + D-gal, Astaxanthin (Ast) + D-gal, Normal Aged (NA), Curcumin (30mg/kg Orally) + NA, Ast (20mg/kg Orally) + NA. Retention and freezing memories were assessed by passive avoidance (PA) and contextual fear conditioning (CFC). Molecular docking was performed to predict curcumin binding with potential molecular targets. Curcumin significantly increased retention time (p < 0.05) and freezing response (p < 0.05) in PA and CFC, respectively. Curcumin profoundly ameliorated the levels of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation in mice hippocampi. In silico studies revealed favorable binding energies of curcumin with GSTA1, GSTO1, KEAP1, BACE1, and MAOA. Curcumin improves retention and freezing memory in D-gal and nature-induced aging mice. Curcumin ameliorates the levels of oxidative stress biomarkers in mice. Anti-aging effects of curcumin could be attributed to, at least partially, the upregulation of antioxidant enzymes through binding with GSTA1, GSTO1, KEAP1, and inhibition of oxidative damage through binding with BACE1 and MAOA.

Topics: Aging; Amyloid Precursor Protein Secretases; Animals; Antioxidants; Aspartic Acid Endopeptidases; Curcumin; Galactose; Glutathione Transferase; Kelch-Like ECH-Associated Protein 1; Memory Disorders; Mice; Molecular Docking Simulation; NF-E2-Related Factor 2; Oxidative Stress

The effect of curcumin (Cur) on cognitive impairment and the possible role of brain tissue oxidative stress, nitric oxide (NO) levels, and brain-derived neurotrophic factor (BDNF) were investigated in juvenile hypothyroid rats. The juvenile rats (21 days old) were allocated into the following groups: (1) control; (2) hypothyroid (0.05% propylthiouracil (PTU) in drinking water); (3-5) hypothyroid-Cur 50, 100, and 150, which in these groups 50, 100, or 150 mg/kg, Cur was orally administered by gavage during 6 weeks. In the hypothyroid rats, the time elapsed and the traveled distance to locate the hidden platform in the learning trials of Morris water maze (MWM) increased, and on the probe day, the amount of time spent in the target quadrant and the distance traveled in there was decreased. Hypothyroidism also decreased the latency and increased the time spent in the darkroom of the passive avoidance (PA) test. Compared with the hypothyroid group, Cur enhanced the performance of the rats in both MWM and PA tests. In addition, Cur reduced malondialdehyde concentration and NO metabolites; however, it increased thiol content as well as the activity of catalase (CAT) and superoxide dismutase enzymes in both the cortex and hippocampus. Cur also increased hippocampal synthesis of BDNF in hypothyroid rats. The beneficial effects of Cur cognitive function in juvenile hypothyroid rats might be attributed to its protective effect against oxidative stress and potentiation of BDNF production.

Topics: Animals; Brain-Derived Neurotrophic Factor; Catalase; Curcumin; Drinking Water; Hippocampus; Hypothyroidism; Malondialdehyde; Maze Learning; Memory Disorders; Nitric Oxide; Oxidative Stress; Propylthiouracil; Rats; Rats, Wistar; Sulfhydryl Compounds; Superoxide Dismutase

Although a substantial body of research suggests curcumin (CUR) has the preventive potential in memory impairment, the mechanism by which CUR prevents memory loss is still being investigated. This study employs an inhibitory avoidance (IA) model to investigate whether CUR can prevent morphine (Mor)-induced memory impairment as well as the possible role of cAMP-response element binding (CREB) protein, and nitric oxide (NO) signaling in this mechanism.. This experimental study was conducted at the Animal Lab of the Physiology Research Center, Kashan University of Medical Sciences (Kashan, Iran) in 2018. Forty rats were randomly divided into four groups: control, CUR (pretreatment gavage of CUR [10 mg/Kg] for 35 days), Mor (7.5 mg/Kg, i.p.), and CUR+Mor (n=10 per group). Following the evaluation of the IA memory and locomotor activity of the animals, the CREB protein expression in the hippocampus and NO metabolites (NOx) level in the brain tissue were also investigated. The data were analyzed using Sigmaplot software (version 14.0) by using the ANOVA, Kruskal-Wallis, Holm-Sidak, and Dunn's. In the Mor group, the IA memory of the rats was significantly impaired (P=0.001). CUR prevented the Mor-induced IA memory impairment (P=0.075). While the Mor treatment decreased the phosphorylated CREB (p-CREB) expression, the CUR+Mor cotreatment increased p-CREB expression (P=0.010). Nevertheless, the Mor treatment increased the total CREB expression (P=0.010). The NOx concentration in the brain tissue was decreased following the Mor treatment (P=0.500) but increased after the CUR+Mor cotreatment (P=0.001).. The present findings suggest that CUR prevents the memory impairment of rats, possibly through NO and its downstream CREB signaling.

Topics: Animals; Curcumin; Cyclic AMP Response Element-Binding Protein; Memory Disorders; Morphine; Nitric Oxide; Rats; Response Elements

Memory deficit is a common cognitive comorbid in patients with neuropathic pain that need better treatment. Recent research revealed that nanocurcumin has an antinociceptive action and a protective effect against memory disorders, suggesting its possible effectiveness for the treatment of neuropathic pain and its comorbidity.. Adult male albino Wistar rats (n = 32) were randomly divided into four experimental groups: CCI+ nanocurcumin, CCI + vehicle, sham + nanocurcumin, and sham + vehicle. Neuropathic pain induced by a chronic constriction injury of the sciatic nerve. Nanocurcumin or vehicle was injected intraperitoneally for 10 days. Behavioral assessment achieved to evaluate pain threshold in the von Frey test and radiant heat test, also spatial learning and memory examined by the Morris water maze (MWM) test. To explore the possible relation, IL-1β, and TNF-α levels of the hippocampus measured by enzyme-linked immunosorbent assay (ELISA).. Our data showed that CCI caused neuropathic pain-related behaviors and spatial learning and memory disorders in rats. Chronic treatment with nanocurcumin significantly increased pain threshold (P < 0.001; F = 27.63, F = 20.58), improved spatial memory (P < 0.01; F = 47.37), and decreased the hippocampal levels of IL-1β (P < 0.001; F = 33.57) and TNF-α (P < 0.01; F = 7.25) in CCI rats.. Chronic nanocurcumin can ameliorate pain-related behavior, improve spatial learning and memory deficits, and is associated with the reduction of IL-1β and TNF-α levels in the hippocampus in CCI rats. Nanocurcumin may be potentially providing a therapeutic alternative for the treatment of neuropathic pain and its memory impairment comorbidity.

Topics: Analgesics; Animals; Behavior, Animal; Constriction; Curcumin; Disease Models, Animal; Hippocampus; Interleukin-1beta; Male; Memory Disorders; Nanoparticles; Neuralgia; Pain Threshold; Rats; Rats, Wistar; Sciatic Nerve; Spatial Memory; Tumor Necrosis Factor-alpha

Curcumin, a major component of Indian saffron through clinical studies, revealed its neuroprotective effect in neurodegenerative diseases. However, it has not been utilized alone orally due to its low bioavailability. There are certain strategies to overcome the drawbacks such as poor absorption and low aqueous solubility. Many strategies are utilized to increase the systemic availability of curcumin. Among them, the steady intestinal and liver metabolism of curcumin by a curcumin adjuvant (enzyme inhibitor/inducer) is an important and less engrossed strategy for improving the overall systemic bioavailability of curcumin. Here, we assess the effect of probiotic Lactobacillus rhamnosus as a curcumin adjuvant (potentiate the effect of curcumin) in scopolamine-induced dementia in mice. To induce amnesia, scopolamine was used in a mouse model (1 mg/kg, daily for 10 days i.p.). After execution of behavioural tests (Morris water maze test), brains and liver were isolated for further neurochemical and histopathology examination. Our results showed a significant increase in antioxidant enzyme levels in curcumin with a probiotic group compared with curcumin alone. Besides, histopathology study results showed less neuronal damage of curcumin with probiotics as compared with the curcumin and scopolamine alone groups. Additionally, curcumin with probiotics improved memory and cognitive functions in the behavioural study with the significance of p ≤ 0.0001. In conclusion, curcumin with probiotics has greater activity as compared with curcumin alone and reverses the hallmarks of Alzheimer's disease (AD).

Topics: Alzheimer Disease; Animals; Cholinergic Antagonists; Curcumin; Drug Synergism; Female; Lacticaseibacillus rhamnosus; Maze Learning; Memory Disorders; Mice; Neuroprotective Agents; Probiotics; Scopolamine

Bile duct ligation (BDL) in rodents can cause impaired liver function and cognition deficits. Curcumin has shown a preventive and therapeutic role in memory impairment.. Therefore, this study aimed to explore the effect of curcumin on the performance of male adult Wistar rats that underwent BDL, a model of hepatic encephalopathy (HE) in the Morris water maze (MWM).. Four weeks after surgery, sham (manipulation of common bile duct without ligation) and BDL rats underwent the MWM test.. The representative data showed that BDL rats exhibited impairments in spatial learning and reference memory in the MWM compared with the sham rats. Treatment of BDL rats with curcumin (40 mg/kg, i.p., for 4 weeks) prevented these impairments, while it did not affect spatial learning and memory in the sham rats, by itself. Curcumin increased expression levels of the pro-survival B cell lymphoma extra-large (Bcl-xL) gene and two genes involved in mitochondrial function, peroxisome proliferative-activated receptor-γ co-activator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM), in the hippocampus of BDL rats compared with the vehicle-treated sham or BDL rats, while it decreased the pro-apoptotic Bcl-2-associated X protein (Bax) gene expression level. BDL up-regulated Bax and down-regulated TFAM, by itself. Furthermore, curcumin reduced the mRNA level of Bax, while it increased Bcl-2 and TFAM mRNA levels.. These findings demonstrate the beneficial effect of curcumin on cognitive function in BDL rats of the HE model. The curcumin effect may be related to mitochondrial function improvement in the HE.

Topics: Animals; Bile Ducts; Cognition; Cognition Disorders; Curcumin; Disease Models, Animal; Hepatic Encephalopathy; Hippocampus; Ligation; Male; Maze Learning; Memory Disorders; PPAR gamma; Rats; Rats, Wistar

Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by massive neuronal degeneration in the striatum. In this study, we utilized solid lipid curcumin particles (SLCPs) and solid lipid particles (SLPs) to test their efficacy in reducing deficits in YAC128 HD mice. Eleven-month-old YAC128 male and female mice were treated orally with SLCPs (100 mg/kg) or equivalent volumes of SLPs or vehicle (phosphate-buffered saline) every other day for eight weeks. Learning and memory performance was assessed using an active-avoidance task on week eight. The mice were euthanized, and their brains were processed using Golgi-Cox staining to study the morphology of medium spiny neurons (MSNs) and Western blots to quantify amounts of DARPP-32, brain-derived neurotrophic factor (BDNF), TrkB, synaptophysin, and PSD-95. We found that both SLCPs and SLPs improved learning and memory in HD mice, as measured by the active avoidance task. We also found that SLCP and SLP treatments preserved MSNs arborization and spinal density and modulated synaptic proteins. Our study shows that SLCPs, as well as the lipid particles, can have therapeutic effects in old YAC128 HD mice in terms of recovering from HD brain pathology and cognitive deficits.

Topics: Animals; Biomarkers; Brain-Derived Neurotrophic Factor; Curcumin; Dendritic Spines; Disease Models, Animal; Dopamine and cAMP-Regulated Phosphoprotein 32; Huntington Disease; Learning; Liposomes; Memory; Memory Disorders; Mice; Mice, Transgenic; Neurons; Receptor, trkB

Previous studies have shown that seizures can cause cognitive disorders. On the other hand, the Curcuma zedoaria (CZ) has beneficial effects on the nervous system. However, there is little information on the possible effects of the CZ extract on seizures. The aim of this study was to investigate the possible effects of CZ extract on cognitive impairment and oxidative stress induced by epilepsy in rats.. Rats were randomly divided into different groups. In all rats (except the sham group), kindling was performed by intraperitoneal injection of pentylenetetrazol (PTZ) at a dose of 35 mg/kg every 48 h for 14 days. Positive group received 2 mg/kg diazepam + PTZ; treatment groups received 100, 200 or 400 mg/kg CZ extract + PTZ; and one group received 0.5 mg/kg flumazenil and CZ extract + PTZ. Shuttle box and Morris Water Maze tests were used to measure memory and learning. On the last day of treatments PTZ injection was at dose of 60 mg/kg, tonic seizure threshold and mortality rate were recorded in each group. After deep anesthesia, blood was drawn from the rats' hearts and the hippocampus of all rats was removed.. Statistical analysis of the data showed that the CZ extract significantly increased the tonic seizure threshold and reduced the pentylenetetrazol-induced mortality and the extract dose of 400 mg/kg was selected as the most effective dose compared to the other doses. It was also found that flumazenil (a GABA. It is concluded that the CZ extract has beneficial effects on learning and memory impairment in PTZ-induced epilepsy model, which has been associated with antioxidant effects in the brain or possibly exerts its effects through the GABAergic system.

Topics: Animals; Anticonvulsants; Antioxidants; Brain Chemistry; Convulsants; Curcuma; Flumazenil; GABA Modulators; Learning Disabilities; Male; Malondialdehyde; Maze Learning; Memory Disorders; Nitric Oxide; Oxidative Stress; Pentylenetetrazole; Plant Extracts; Rats; Rats, Wistar; Seizures

A series of novel chalcone-O-alkylamine derivatives were designed, synthesized and evaluated as multifunctional anti-Alzheimer's disease agents. Based on the experimental results, compound 23c exhibited good inhibitory potency on both acetylcholinesterase (IC

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Biological Transport; Blood-Brain Barrier; Butyrylcholinesterase; Chalcones; Chelating Agents; Cholinesterase Inhibitors; Coordination Complexes; Copper; Drug Design; Female; Humans; Male; Memory Disorders; Mice; Molecular Docking Simulation; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neuroprotective Agents; Protein Binding; Scopolamine; Structure-Activity Relationship

Unpredictable chronic mild stress (UCMS) model is the most established method to study neurobiological mechanisms of depression. This work was intended to explore the efficacy of curcumin to revert the UCMS-induced oxidative burden and associated depression as well as potential of curcumin as an acetyl cholinesterase (AchE) inhibitor. Animals were initially grouped into control and curcumin (200mg/kg, p.o) and further subdivided into unstressed and stressed groups. Depression and anxiety were evaluated by forced swim test (FST) and light/dark transition (LDT) while memory function was assessed by passive avoidance test (PAT). Effect of curcumin on oxidative stress following UCMS was determined by measuring peroxidation of lipid (LPO) and antioxidant enzyme activities. AchE activity was also determined. Findings showed that curcumin supplementation significantly attenuated the UCMS-induced depression and anxiety like symptoms, decreased the load of UCMS propagated oxidative stress by improving antioxidant enzymes activities. Curcumin also improved the memory function and exhibited inhibitory effect on AchE activity. In conclusion it can be suggested that supplementation of curcumin in daily life can help in combating the stress-induced depression and ever increasing load of oxidative stress. Study also highlights the anti-acetylcholinesterase potential of curcumin which may be responsible for improved memory function following UCMS.

Topics: Acetylcholinesterase; Animals; Antioxidants; Anxiety; Cholinesterase Inhibitors; Curcumin; Depression; Lipid Peroxidation; Male; Maze Learning; Memory; Memory Disorders; Mice; Oxidative Stress; Rats, Wistar; Stress, Psychological

Curcumin is a natural product with several anti-Alzheimer's disease (AD) neuroprotective properties. This study aimed to investigate the effects of curcumin on memory deficits, lactate content, and monocarboxylate transporter 2 (MCT2) in APP/PS1 mouse model of AD. APP/PS1 transgenic mice and wild-type (WT) C57BL/6J mice were used in the present study. Spatial learning and memory of the mice was detected using Morris water-maze test. Cerebral cortex and hippocampus lactate contents were detected using lactate assay. MCT2 expression in the cerebral cortex and hippocampus was examined by immunohistochemistry and Western blotting. Results showed that spatial learning and memory deficits were improved in curcumin-treated APP/PS1 mouse group compared with those in APP/PS1 mice group. Brain lactate content and MCT2 protein level were increased in curcumin-treated APP/PS1 mice than in APP/PS1 mice. In summary, our findings indicate that curcumin could ameliorate memory impairments in APP/PS1 mouse model of AD. This phenomenon may be at least partially due to its improving effect on the lactate content and MCT2 protein expression in the brain. Anat Rec, 302:332-338, 2019. © 2018 Wiley Periodicals, Inc.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Female; Lactic Acid; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Mice, Transgenic; Monocarboxylic Acid Transporters; Presenilin-1

Curcumin is a polyphenol natural product of the plant Curcuma longa. Recent studies suggest that curcumin inhibit mTOR activity in vitro, which prompts us to investigate curcumin function as a new class of mTOR inhibitor suitable for tuberous sclerosis complex (TSC) treatment.. We aim to investigate the efficacy of curcumin in the treatment of TSC related manifestations in animal model.. Solid lipid curcumin particle (SLCP), a novel curcumin formulation, was used to treat TSC related manifestations in Tsc2 knockout mice.. The novel object recognition test was used to analyze the recognition memory function. The long-term potentiation was studied using electrophysiological analysis. Western blotting was used to assess the protein expression and activation status.. Recognition memory deficit began as early as 4 weeks of age in both male and female Tsc2. Our results suggest that SLCP could be an effective treatment for TSC patients.

Topics: Administration, Oral; Animals; Brain; Curcumin; Disease Models, Animal; Female; Humans; Long-Term Potentiation; Male; Memory Disorders; Mice, Knockout; Protein Kinase Inhibitors; TOR Serine-Threonine Kinases; Tuberous Sclerosis; Tuberous Sclerosis Complex 2 Protein

Our aim was to investigate the effects of resveratrol, auraptene, and curcumin on the spatial learning and spatial memory retention in the Morris water maze (MWM). The effects of 4-day bilateral intrahippocampal (i.h.) infusions of dimethyl sulfoxide (DMSO), H-89 as a protein kinase AII inhibitor, auraptene/H-89, resveratrol/H-89, and curcumin/H-89 were investigated on spatial memory acquisition in MWM. The rats were trained for 4 days; each day included one block of four trials. Post-training probe tests were performed on day 5 in acquisition test. For retention assessments, different animals were trained for 4 days and then infused (i.h.) with either DMSO, H-89, auraptene/H-89, resveratrol/H-89, or curcumin/H-89. The retention test was performed 48 h after the last training trial. The bilateral infusion of H-89 led to a significant impairment in spatial memory in acquisition and retention tests accompanied with a significant decrease in expressions of cAMP response-element binding (CREB) and pCREB proteins in hippocampus. Resveratrol and curcumin reversed the H-89-induced spatial memory acquisition and retention impairments with significant increases in both CREB and pCREB proteins expressions compared to H-89-treated animals. Auraptene showed significant effects in reversing H-89-induced impairments in spatial memory retention but not spatial memory acquisition.

Topics: Animals; Coumarins; Curcumin; Cyclic AMP Response Element-Binding Protein; Hippocampus; Infusions, Parenteral; Isoquinolines; Male; Memory; Memory Disorders; Neuroprotective Agents; Rats, Wistar; Resveratrol; Sulfonamides

The aim of the current study was to explore the underlying neuroprotective mechanisms of curcumin (50 mg/kg, for six weeks) against ethanol (5 mg/kg i.p., for six weeks) induced oxidative stress and inflammation-mediated cognitive dysfunction in mice. According to our findings, ethanol triggered reactive oxygen species (ROS), apoptosis, neuroinflammation, and memory impairment, which were significantly inhibited with the administration of curcumin, as assessed by ROS, lipid peroxidation (LPO), and Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/Heme-oxygenase-1) expression in the experimental mice brains. Moreover, curcumin regulated the expression of the glial cell markers in ethanol-treated mice brains, as analyzed by the relative expression TLR4 (Toll like Receptor 4), RAGE (Receptor for Advanced Glycations End products), GFAP (Glial fibrillary acidic protein), and Iba-1 (Ionized calcium binding adaptor molecule 1), through Western blot and confocal microscopic analysis. Moreover, our results showed that curcumin downregulated the expression of p-JNK (Phospo c-Jun N-Terminal Kinase), p-NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), and its downstream targets, as assessed by Western blot and confocal microscopic analysis. Finally, the expression of synaptic proteins and the behavioral results also supported the hypothesis that curcumin may inhibit memory dysfunction and behavioral alterations associated with ethanol intoxication. Altogether, to the best of our knowledge, we believe that curcumin may serve as a potential, promising, and cheaply available neuroprotective compound against ethanol-associated neurodegenerative diseases.

Topics: Animals; Cell Line; Curcumin; Dietary Supplements; Gene Expression Regulation; Hippocampus; Lipid Peroxidation; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Microglia; Neurodegenerative Diseases; Neurons; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species; Receptor for Advanced Glycation End Products; RNA Interference; RNA, Small Interfering; Toll-Like Receptor 4

Despite its poor bioavailability, curcumin is a promising natural polyphenol targeting NF-κβ. NF-κβ is a target for new therapeutics because it plays a pivotal role in the pathophysiology of Alzheimer disease (AD). In contrast, ambrsoin, a sesquiterpene lactone which is a potent NF-κβ inhibitor, is scarcely studied in AD models. The current work aims to assess the efficacy of ambrosin as a possible remedy for AD. In silico studies showed that bioavailability and BBB permeability could be favorable for ambrosin over curcumin. Memory impairment was induced in mice by single intraperitoneal injection of LPS (0.4 mg/kg). Treated groups received curcumin (100 mg/kg) or ambrosin at doses (5 or 10 mg/kg) for 7 days. Mice in treated groups showed a significant improvement in memory functions during Morris water maze and object recognition tests. Curcumin and ambrosin (10 mg/kg) inhibited the upsurge of NF-κβp65 transcript and protein levels. Consequently, downstream pro-inflammatory and nitrosative mediators were inhibited, namely, TNF-α, IL-1β, COX-2 and iNOS. BACE1 was inhibited, thereby reducing amyloid plaques (Aβ) deposition and eventually reducing inflammation and apoptosis of neurons as revealed by immunohistopathological examination. In conclusion, ambrosin can be repurposed as AD remedy after further pharmacokinetic/pharamacodynamic assessments. It could serve as an additional lead drug for AD therapeutics.

Topics: Amyloid beta-Peptides; Animals; Apoptosis; Biomarkers; Curcumin; Cytokines; Disease Models, Animal; Inflammation Mediators; Lipopolysaccharides; Male; Maze Learning; Memory; Memory Disorders; Mice; Molecular Structure; NF-kappa B; Plant Extracts; Sesquiterpenes, Guaiane; Signal Transduction; Structure-Activity Relationship

A novel series of quinoline-indole derivatives were synthesized and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease (AD). Biological evaluation revealed that the derivatives had multifunctional profiles including antioxidant effects, blood-brain barrier (BBB) penetration, biometal chelation, Aβ aggregation modulation, neurotrophic and neuroprotective properties. Moreover, several representative target derivatives demonstrated hippocampal cell proliferation in living adult mice by intracerebroventricular (icv) injection or oral administration. Further drug-like property analysis demonstrated that the optimized compound, 8d (WI-1758), had liver microsomal metabolic stability, was well tolerated (>2000 mg/kg), and had a rational pharmacokinetic profile, as well as an oral bioavailability of 14.1% and a positive log BB (-0.19) to cross the BBB in vivo. Pharmacodynamics studies demonstrated that chronic oral administration of 8d·HCl substantially ameliorated the cognitive and spatial memory deficits in APP/PS1 AD mice and noticeably reduced overall cerebral β-amyloid deposits.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Blood-Brain Barrier; Cell Proliferation; Drug Design; Hippocampus; Humans; Indoles; Ligands; Memory Disorders; Mice; Quinolines

The loss of cholinergic neurons has been a major issue in researches on Alzheimer's disease (AD) for about 40 years. Therefore, the scopolamine model of amnesia has been widely used in AD researches. Recently, it was reported that the early stage amnesia of AD is related to memory retrieval deficit. Curcumin, as the main ingredient of turmeric, has been suggested to decrease the prevalence of AD in human population. This study was conducted to assess if curcumin prevents retrieval deficit induced by scopolamine in passive avoidance task. Moreover, according to the proposed link between cholinergic system and Akt/GSK-3β (Glycogen synthase kinase 3 beta) signaling, the hippocampal contents of these proteins were determined. Male NMRI mice (20-25 g body weight) were treated with 50 or 100 mg/kg/po curcumin or its vehicle for 10 days. On day 10, the animals were trained in passive avoidance apparatus. The retention trial was performed 24 h later. Scopolamine (1 mg/kg/i.p.) or its vehicle was administered 30 min before retention test. At the completion of behavioral studies, the hippocampi were removed and western blot analysis was performed to determine hippocampal phosphorylated and total Akt and GSK-3β and beta actin contents. The results showed that curcumin treatment at 50 and 100 mg/kg doses prevented scopolamine-induced memory retrieval deficit and restored Akt and GSK dephosphorylation caused by scopolamine. Overall, these findings showed that pre-test scopolamine administration disrupts memory retrieval along with the diminished Akt and GSK-3β phosphorylation in hippocampus while curcumin administration prevented those changes.

Topics: Animals; Avoidance Learning; Curcumin; Glycogen Synthase Kinase 3 beta; Hippocampus; Male; Memory Disorders; Mice; Phosphoproteins; Proto-Oncogene Proteins c-akt; Scopolamine

Protection of neurons from degeneration is an important preventive strategy for dementia. Much of the dementia pathology implicates oxidative stress pathways. Turmeric (Curcuma longa L.) contains curcuminoids which has anti-oxidative and neuro-protective effects. These effects are considered to be similar to those of citicoline which has been regularly used as one of standard medications for dementia.. This study aimed at investigating the effects of turmeric rhizome extract on the hippocampus of trimethyltin (TMT)-treated Sprague-Dawley rats.. The rats were divided randomly into six groups, i.e., a normal control group (N); Sn group, which was given TMT chloride; Sn-Cit group, which was treated with citicoline and TMT chloride; and three Sn-TE groups, which were treated with three different dosages of turmeric rhizome extract and TMT chloride. Morris water maze test was carried out to examine the spatial memory. The estimated total number of CA1 and CA2-CA3 pyramidal cells was calculated using a stereological method.. The administration of turmeric extract at a dose of 200 mg/kg bw has been shown to prevent the deficits in the spatial memory performance and partially inhibit the reduction of the number of CA2-CA3 regions pyramidal neurons.. TMT-induced neurotoxic damage seemed to be mediated by the generation of reactive oxygen species and reactive nitrogen species. Turmeric extract might act as anti inflammatory as well as anti-oxidant agent.. The effects of turmeric extract at a dose of 200 mg/kg bw seem to be comparable to those of citicoline.

Topics: Animals; Behavior, Animal; Curcuma; Cytidine Diphosphate Choline; Disease Models, Animal; Hippocampus; Male; Maze Learning; Memory Disorders; Nerve Degeneration; Neuroprotective Agents; Nootropic Agents; Phytotherapy; Plant Extracts; Plants, Medicinal; Pyramidal Cells; Rats, Sprague-Dawley; Reactive Nitrogen Species; Reactive Oxygen Species; Rhizome; Spatial Memory; Time Factors; Trimethyltin Compounds

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Blood-Brain Barrier; Butyrylcholinesterase; Cholinesterase Inhibitors; Coumaric Acids; Drug Design; Eels; Humans; Memory Disorders; Mice; PC12 Cells; Rats

Curcuma longa L. is a well-known medicinal plant that has been used for its anti-cancer, neuroprotective, and hepatoprotective effects. However, the neuroprotective effect of fermented C. longa (FCL) has not been reported. Therefore, in this study, the effectiveness of FCL for the regulation of memory dysfunction was investigated in two brain cell lines (rat glioma C6 and murine microglia BV2) and scopolamine-treated mice.. Pretreatment with FCL effectively prevented the cell death induced by oxidative stress in C6 cells. Moreover, FCL inhibited the production NO and PGE. FCL pretreatment could alleviate scopolamine-induced memory impairment in mice, as well as oxidative stress and inflammation in C6 and BV2 cells, respectively. Thus, FCL might be a useful material for preventing impairment of learning and memory.

Topics: Acetylcholinesterase; Amnesia; Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Brain-Derived Neurotrophic Factor; Cell Line; Curcuma; Curcumin; Cyclic AMP Response Element-Binding Protein; Fermentation; Inflammation; Inflammation Mediators; Lipopolysaccharides; Male; Memory Disorders; Mice, Inbred ICR; Neuroprotective Agents; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Scopolamine

Despite several beneficial effects of curcumin, its medical application has been hampered due to low water solubility. To improve the aqueous solubility of curcumin, it has been loaded on chitosan (CS)-alginate (ALG) - sodium tripolyphosphate (STPP) nanoparticles (NPs). Then, the effect of curcumin NPs on memory improvement and glial activation was investigated in pentylenetetrazol (PTZ)-induced kindling model. Male NMRI mice have received the daily injection of curcumin NPs at dose of 12.5 or 25mg/kg. All interventions were injected intraperitoneally (i.p), 10days before PTZ administration and the injections were continued until 1h before each PTZ injection. Spatial learning and memory was evaluated using Morris water maze test after the 7th PTZ injection. Animals have received 10 injections of PTZ and then, brain tissues were removed for histological evaluation. Nissl staining was used to determine the level of cell death in hippocampus and immunostaining method was performed against NeuN and GFAP/Iba1 for assessment of neuronal density and glial activation respectively. Behavioral results showed that curcumin NPs exhibit anticonvulsant activity and prevent cognitive impairment in fully kindled animals. The level of cell death and glial activation reduced in animals which have received curcumin NPs compared to those received free curcumin. To conclude, these findings suggest that curcumin NPs effectively ameliorate memory impairment and attenuate the level of activated glial cells in a mice model of chronic epilepsy.

Topics: Animals; Anticonvulsants; Brain; Chronic Disease; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Carriers; Epilepsy; Injections, Intraperitoneal; Kindling, Neurologic; Male; Memory Disorders; Mice; Nanoparticles; Neuroglia; Nootropic Agents; Pentylenetetrazole; Random Allocation; Spatial Learning; Spatial Memory

The present study examined the consequences of rapid eye-movement sleep-deprivation (REM-SD) with or without curcumin treatment. The outcome measures comprised quantitative features in the three-dimensional reconstruction (3DR) CA1 and dentate gyrus in experimental and control animals using stereological procedures. Male rats were arbitrarily assigned to nine groups based on the intervention and treatment administered including: 1-cage control+distilled water, 2-cage control+curcumin (100mg/kg/day), 3-cage control+olive oil, 4-REM-SD+distilled water, 5-REM-SD+curcumin, 6-REM-SD+olive oil, 7-grid-floor control+distilled water, 8-grid-floor control+curcumin, and 9-grid-floor control+olive oil. Animals in the latter three groups were placed on wire-mesh grids in the sleep-deprivation box. REM-SD was induced by an apparatus comprising a water tank and multiple platforms. After a period of 21days, rats were submitted to the novel object-recognition task. Later, their brains were excised and evaluated using stereological methods. Our results indicated a respective 29% and 31% reduction in the total volume of CA1, and dentate gyrus in REM-SD+distilled water group as compared to the grid-floor control+distilled water group (p<0.05). Other than the above, the overall number of the pyramidal cells of CA1 and granular cells of dentate gyrus in the sleep-deprived group were found to be reduced by 48% and 25%, respectively. The REM-SD+distilled water group also exhibited impaired object recognition memory and deformed three-dimensional reconstructions of these regions. The volume, cell number, reconstruction, object recognition time, and body weight were however recovered in the REM-SD+curcumin compared to the REM-SD+distilled water group. This suggests the potential neuro-restorative effects of curcumin in our model.

Topics: Animals; Body Weight; Cell Size; Curcumin; Dentate Gyrus; Hippocampus; Imaging, Three-Dimensional; Male; Memory Disorders; Rats; Rats, Sprague-Dawley; Recognition, Psychology; Sleep Deprivation; Sleep, REM

Several studies have indicated that neuroinflammation is indeed associated with neurodegenerative disease pathology. However, failures of recent clinical trials of anti-inflammatory agents in neurodegenerative disorders have emphasized the need to better understand the complexity of the neuroinflammatory process in order to unravel its link with neurodegeneration. Deregulation of Cyclin-dependent kinase 5 (Cdk5) activity by production of its hyperactivator p25 is involved in the formation of tau and amyloid pathology reminiscent of Alzheimer's disease (AD). Recent studies show an association between p25/Cdk5 hyperactivation and robust neuroinflammation. In addition, we recently reported the novel link between the p25/Cdk5 hyperactivation-induced inflammatory responses and neurodegenerative changes using a transgenic mouse that overexpresses p25 (p25Tg). In this study, we aimed to understand the effects of early intervention with a potent natural anti-inflammatory agent, curcumin, on p25-mediated neuroinflammation and the progression of neurodegeneration in p25Tg mice. The results from this study showed that curcumin effectively counteracted the p25-mediated glial activation and pro-inflammatory chemokines/cytokines production in p25Tg mice. Moreover, this curcumin-mediated suppression of neuroinflammation reduced the progression of p25-induced tau/amyloid pathology and in turn ameliorated the p25-induced cognitive impairments. It is widely acknowledged that to treat AD, one must target the early-stage of pathological changes to protect neurons from irreversible damage. In line with this, our results demonstrated that early intervention of inflammation could reduce the progression of AD-like pathological outcomes. Moreover, our data provide a rationale for the potential use of curcuminoids in the treatment of inflammation associated neurodegenerative diseases.

Topics: Alzheimer Disease; Animals; Anti-Inflammatory Agents; Astrocytes; Brain; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Curcumin; Humans; Inflammation; Memory Disorders; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; Nerve Degeneration; Neuroimmunomodulation; Neuroprotective Agents; Nootropic Agents

This study investigated the protective effect of curcumin on memory loss and on the alteration of acetylcholinesterase and ectonucleotidases activities in rats exposed chronically to cadmium (Cd). Rats received Cd (1 mg/kg) and curcumin (30, 60, or 90 mg/kg) by oral gavage 5 days a week for 3 months. The animals were divided into eight groups: vehicle (saline/oil), saline/curcumin 30 mg/kg, saline/curcumin 60 mg/kg, saline/curcumin 90 mg/kg, Cd/oil, Cd/curcumin 30 mg/kg, Cd/curcumin 60 mg/kg, and Cd/curcumin 90 mg/kg. Curcumin prevented the decrease in the step-down latency induced by Cd. In cerebral cortex synaptosomes, Cd-exposed rats showed an increase in acetylcholinesterase and NTPDase (ATP and ADP as substrates) activities and a decrease in the 5'-nucleotidase activity. Curcumin was not able to prevent the effect of Cd on acetylcholinesterase activity, but it prevented the effects caused by Cd on NTPDase (ATP and ADP as substrate) and 5'-nucleotidase activities. Increased acetylcholinesterase activity was observed in different brain structures, whole blood and lymphocytes of the Cd-treated group. In addition, Cd increased lipid peroxidation in different brain structures. Higher doses of curcumin were more effective in preventing these effects. These findings show that curcumin prevented the Cd-mediated memory impairment, demonstrating that this compound has a neuroprotective role and is capable of modulating acetylcholinesterase, NTPDase, and 5'-nucleotidase activities. Finally, it highlights the possibility of using curcumin as an adjuvant against toxicological conditions involving Cd exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 70-83, 2017.

Topics: Animals; Avoidance Learning; Cadmium Poisoning; Curcumin; Dose-Response Relationship, Drug; Electroshock; Lipid Peroxidation; Male; Memory Disorders; Motor Activity; Parasympathetic Nervous System; Rats; Rats, Wistar; Receptors, Purinergic; Signal Transduction; Synaptosomes

Alzheimer's disease (AD) is the most common dementia and the trigger of its pathological cascade is widely believed to be the overproduction and accumulation of β-amyloid protein (Aβ) in the affected brain. However, effective AD remedies are still anxiously awaited. Recent evidence suggests that curcumin may be a potential agent for AD treatment. In this study, we used 5×FAD transgenic mice as an AD model to investigate the effects of curcumin on AD. Our results showed that curcumin administration (150 or 300 mg/kg/day, intragastrically, for 60 days) dramatically reduced Aβ production by downregulating BACE1 expression, preventing synaptic degradation, and improving spatial learning and memory impairment of 5×FAD mice. These findings suggest that curcumin is a potential candidate for AD treatment.

Topics: Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspartic Acid Endopeptidases; Curcumin; Gene Expression; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peptide Fragments

Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes has been reported to exert cognitive enhancing potential with limited scientific basis. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities in cadmium (Cd)-induced memory impairment in rats. Animals were divided into six groups (n = 6): saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. Rats received Cd (2.5 mg/kg) and curcumin (12.5 and 25 mg/kg, respectively) by gavage for 7 days. The results of this study revealed that cerebral cortex AChE and ADA activities were increased in Cd-poisoned rats, and curcumin co-treatment reversed these activities to the control levels. Furthermore, Cd intoxication increased the level of lipid peroxidation in cerebral cortex with a concomitant decreased in functional sulfuhydryl (-SH) group and nitric oxide (NO), a potent neurotransmitter and neuromodulatory agent. However, the co-treatment with curcumin at 12.5 and 25 mg/kg, respectively increased the non-enzymatic antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde (MDA) level. Therefore, inhibition of AChE and ADA activities as well as increased antioxidant status by curcumin in Cd-induced memory dysfunction could suggest some possible mechanism of action for their cognitive enhancing properties.

Topics: Acetylcholinesterase; Adenosine Deaminase; Adenosine Deaminase Inhibitors; Animals; Cadmium Compounds; Cerebral Cortex; Cholinesterase Inhibitors; Curcumin; Male; Malondialdehyde; Memory Disorders; Memory, Episodic; Rats; Spatial Memory; Sulfates

Recently, combination therapy involving cholinesterase (ChE) inhibitor with other neuroprotective agents has shown better desirable effect in the management/prevention of dementia but limited information is available on their effect with dietary polyphenols. Hence, this study sought to assess the combined pretreatment effect of curcumin, the major polyphenolic compound of turmeric (Curcuma longa) rhizomes, with donepezil, a cholinesterase inhibitor, on cognitive function in scopolamine-induced memory impairment in rats. Rats were pretreated with curcumin (50 mg/kg) and/or donepezil (2.5 mg/kg) via oral administration (p.o.) for seven successive days. Dementia was induced at the end of the treatment period by a single injection of scopolamine (1 mg/kg) via intraperitoneal (i.p.) administration. Thereafter, the changes in spatial and episodic memory were conducted; then, the estimation of some biochemical parameters associated with cognitive function was determined. Scopolamine-treated rats showed impaired learning and memory and increased activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), adenosine deaminase (ADA), and lipid peroxidation with a concomitant decreased in levels of nitric oxide (NO) and reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities when compared with control. However, combination of curcumin and donepezil improves learning and memory activity associated with inhibitory effect on AChE, BuChE, and ADA activities as compared to control. In addition, combined pretreatment significantly decreased lipid peroxidation and increased levels of NO and antioxidant status when compared with scopolamine-treated rats. This finding supports the concept that the combination strategy might be an alternative therapy in the management/prevention of neurological disorders. Thus, the observed anti-amnestic effect could be linked to their inhibitory effect on key enzyme of cholinergic system associated with memory function.

Topics: Adenosine Deaminase; Animals; Brain; Catalase; Cholinergic Neurons; Cholinesterase Inhibitors; Curcumin; Donepezil; Drug Synergism; Glutathione; Indans; Lipid Peroxidation; Male; Maze Learning; Memory Disorders; Nitric Oxide; Piperidines; Rats; Recognition, Psychology; Scopolamine; Superoxide Dismutase

Neurons die in Alzheimer's disease (AD) and are not effectively replaced. An alternative approach to maintain nerve cell number is to identify compounds that stimulate the proliferation of endogenous neural stem cells in old individuals to replace lost neurons. However, unless a neurogenic drug is also neuroprotective, the replacement of lost neurons will not be sufficient to stop disease progression.. The neuroprotective AD drug candidate J147 is shown to enhance memory, improve dendritic structure, and stimulate cell division in germinal regions of the brains of very old mice. Based on the potential neurogenic potential of J147, a neuronal stem cell screening assay was developed to optimize derivatives of J147 for human neurogenesis.. The best derivative of J147, CAD-031, maintains the neuroprotective and memory enhancing properties of J147, yet is more active in the human neural stem cell assays.. The combined properties of neuroprotection, neurogenesis, and memory enhancement in a single drug are more likely to be effective for the treatment of age-associated neurodegenerative disorders than any individual activity alone.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Cell Differentiation; Cells, Cultured; Curcumin; Disease Models, Animal; Drug Discovery; Embryonic Stem Cells; Female; Fibroblast Growth Factor 2; Gene Expression Regulation; Humans; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins; Neurons; Neuroprotective Agents; Presenilin-1

In the present study, we examined the ameliorating effects of demethoxycurcumin (DMC) on memory impairment induced by scopolamine using passive avoidance and Morris water maze tests in mice. Moreover, to determine the neurobiological effects underlying the ameliorating effects of the DMC, choline acetyltransferase (ChAT) immunoreactivity was evaluated in mice exposed to scopolamine. Our results demonstrated that chronic oral administration (28 days) of DMC (10 mg/kg) improved scopolamine-induced learning impairment in the passive avoidance task and memory impairment in the Morris water maze. Moreover, Choline acetyltransferase (ChAT) activity in the DMC-treated group was significantly increased to 33.03% compared with the control group. Our present finding suggests that DMC ameliorates memory impairments induced by scopolamine treatment through reversing the reduction of hippocampal ChAT expression in mice.

Topics: Administration, Oral; Animals; Avoidance Learning; Choline O-Acetyltransferase; Curcumin; Diarylheptanoids; Disease Models, Animal; Drug Administration Schedule; Gene Expression Regulation; Male; Maze Learning; Memory Disorders; Mice; Mice, Inbred ICR; Scopolamine

The present study has been designed to investigate the role of curcumin on cisplatin-inducedcognitive impairment and to reveal mechanisms of cisplatin's detrimental actions on cognition in rats. Animals were treated with cisplatin (5mg/kg/week) and/or curcumin (300mg/kg/day) for 5weeks. Morris water maze test was used to assess spatial learning and memory. Enzymatic activities of acetylcholinesterase (AChE) and superoxide dismutase (SOD) were evaluated from hippocampus and plasma samples, and malondialdehyde (MDA), which is the end-product of lipid peroxidation, was determined by a colorimetric method. Our results showed that cisplatin (5mg/kg/week, 5weeks) caused learning and memory deficits, elevated MDA content, decreased SOD activity in the hippocampus and plasma, and AChE activity in the hippocampus. Curcumin improved learning and memory in rats with administration of cisplatin. In addition, curcumin significantly reduced the level of MDA and increased the activities of SOD and AChE. Taken together, our findings indicate that curcumin ameliorates cisplatin-induced spatial learning and memory impairment, possibly through restored cholinergic function and enhanced oxidative status.

Topics: Acetylcholinesterase; Animals; Antineoplastic Agents; Behavior, Animal; Cisplatin; Cognition Disorders; Curcumin; Disease Models, Animal; Hippocampus; Male; Malondialdehyde; Memory Disorders; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Spatial Memory; Superoxide Dismutase

Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer's disease (AD). However, the molecular mechanisms underlying curcumin's effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer's disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain-Derived Neurotrophic Factor; Cognition; Curcumin; Disease Models, Animal; Male; MAP Kinase Signaling System; Maze Learning; Memory Disorders; Memory, Short-Term; Neuroprotective Agents; Peptide Fragments; Rats; Rats, Sprague-Dawley; Signal Transduction; Spatial Memory

Aging is a progressive process, and it may lead to the initiation of neurological diseases. In this study, we investigated the effects of wild Indian Curcuma longa using a Morris water maze paradigm on learning and spatial memory in adult and D-galactose-induced aged mice. In addition, the effects on cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin (DCX) respectively. The aging model in mice was induced through the subcutaneous administration of D-galactose (100 mg/kg) for 10 weeks. C. longa (300 mg/kg) or its vehicle (physiological saline) was administered orally to adult and D-galactose-treated mice for the last three weeks before sacrifice. The administration of C. longa significantly shortened the escape latency in both adult and D-galactose-induced aged mice and significantly ameliorated D-galactose-induced reduction of cell proliferation and neuroblast differentiation in the subgranular zone of hippocampal dentate gyrus. In addition, the administration of C. longa significantly increased the levels of phosphorylated CREB and brain-derived neurotrophic factor in the subgranular zone of dentate gyrus. These results indicate that C. longa mitigates D-galactose-induced cognitive impairment, associated with decreased cell proliferation and neuroblast differentiation, by activating CREB signaling in the hippocampal dentate gyrus.

Topics: Aging; Animals; Brain; Brain-Derived Neurotrophic Factor; Cell Proliferation; Cognition Disorders; CREB-Binding Protein; Curcuma; Curcumin; Doublecortin Protein; Galactose; Male; Maze Learning; Memory Disorders; Mice, Inbred C57BL; Models, Animal; Neurogenesis; Phosphorylation; Phytotherapy; Plant Extracts; Signal Transduction; Spatial Memory; Up-Regulation

Accumulating evidence suggests that cognitive processes, such as learning and memory, are affected in depression and antidepressant treatment may ameliorate cognitive impairments. Recent studies have shown that curcumin exhibits antidepressant-like effects. The aim of the present study was to determine whether curcumin administration influences chronic unpredictable stress (CUS)-induced cognitive deficits and explores underlying mechanisms. Male Wistar rats were subjected to CUS protocol for a period of 5 weeks to induce depression. The depressive-like behavior was tested using sucrose preference test, open field test and Morris water maze test. Effects of curcumin on brain-derived neurotrophic factor (BDNF) and extracellular signal-regulated kinase (ERK) levels in the hippocampus were also examined. Chronic treatment with curcumin significantly reversed the CUS-induced behavioral and cognitive parameters (reduced sucrose preference and impaired learning and memory function) in stressed rats. Additionally, CUS reduced hippocampal BDNF and ERK levels, while curcumin effectively reversed these alterations. Taken together, our results indicate that the antidepressant-like effects of curcumin in CUS rats are related to its aptitude to promote BDNF and ERK in the hippocampus.

Topics: Animals; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Cognition; Curcumin; Depression; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Food Preferences; Hippocampus; Locomotion; Male; Maze Learning; Memory Disorders; Motor Activity; Psychomotor Performance; Rats; Rats, Wistar; Stress, Psychological; Treatment Outcome

Epilepsy is a chronic neurological disorder and generally associated with certain psychiatric comorbidities. Among several comorbidities depressive behavior and cognitive impairment has been reported to be most debilitating comorbidity associated with epilepsy. This study was envisaged to evaluate the ameliorative effect of Curcumin on depression like behavior and cognitive impairment observed in pentylenetetrazole kindled animals. Male Swiss Albino mice were kindled with subconvulsive dose of pentylenetetrazole (35 mg/kg, i.p.). Successfully kindled animals were used in the study to observe the effect of different treatments. Treatment groups received phenytoin (30 mg/kg) and Curcumin (50, 100 and 200mg/kg) for 15 days. The animals were challenged with pentylenetetrazole (35 mg/kg, i.p.) on day 5, 10 and 15 and seizure severity score, immobility period, number of mistakes and step down latency were recorded. On 15th day, all the animals were sacrificed after behavioral evaluations and their brain was isolated and homogenized to estimate brain norepinephrine, serotonin, total nitrite level and acetylcholinesterase activity. Phenytoin treatment significantly improved the depressive like behavior along with its anticonvulsant effect, however was unable to improve memory impairment. Curcumin significantly attenuated seizure severity, depression like behavior and memory impairment in kindled animals, in dose dependent manner. These results were supported by the biochemical modulation of brain monoamine, nitrosative stress level and acetylcholinesterase activity. Thus present study concluded that Curcumin has the ameliorative effect on seizure severity, depression like behavior and memory impairment in pentylenetetrazole kindled mice, possibly via central monoaminergic modulation and inhibitory effect on nitrosative stress and acetylcholinesterase activity.

Topics: Acetylcholinesterase; Animals; Anticonvulsants; Behavior, Animal; Brain; Convulsants; Curcumin; Depression; Hindlimb Suspension; Learning; Male; Memory Disorders; Mice; Nitrates; Nitrites; Norepinephrine; Pentylenetetrazole; Seizures; Serotonin

Ethanol consumption has well-known deleterious effects on memory. However, the mechanism by which ethanol exerts its effects on memory has received little attention, which has retarded the identification and development of effective therapeutic strategies against ethanol toxicity. The aim of this study was to explore the neuronal mechanisms underlying the protective action of curcumin, a natural polyphenolic compound of Curcuma longa, against ethanol-induced memory deficits. Adult mice were pretreated with curcumin (40 mg/kg, i.p.) before administration of ethanol (1 g/kg, i.p.) for the memory acquisition measurement, or were sacrificed 30 min later for evaluation of regional brain differences in the nitric oxide synthase (NOS) activity and nitric oxide (NO) concentration. The results showed that pretreatment with curcumin significantly ameliorated the memory deficits resulting from acute ethanol administration to mice in the novel object recognition and inhibitory avoidance tasks. Furthermore, acute ethanol treatment increased the NOS activity and NO production in brain regions associated with memory including prefrontal cortex (PFC), amygdala and hippocampus, while this enhancement was suppressed by pretreatment with curcumin. Taken together, these results suggest that the protective effects of curcumin on acute ethanol-induced memory deficits are mediated, at least in part, by suppressing NOS activity in the brain of mice. Thus, manipulation of the NOS/NO signaling pathway might be beneficial for the prevention of ethanol toxicity.

Topics: Animals; Brain; Central Nervous System Depressants; Curcumin; Enzyme Inhibitors; Escape Reaction; Ethanol; Exploratory Behavior; Male; Memory Disorders; Mice; Mice, Inbred Strains; Nitric Oxide; Nitric Oxide Synthase; Reaction Time; Recognition, Psychology

Aging induced cognitive impairment has been well documented for many years and several antioxidant strategies have been developed against this impairment. Curcumin is the active component of curcuma longa and has shown antioxidant, antiinflamatory and neuroprotective properties. We hypothesized that curcumin would have an influence on cognitive functions in aged female rats. The purpose of the present study was to investigate the effects of curcumin supplementation on cognitive impairment evaluated by Morris water maze (MWM) as well as the oxidative stress induced by aging in female rats. Rats were randomly divided into either control or curcumin-supplemented groups. Curcumin or vehicle (corn oil) were given once daily for a period of 12 days, beginning 7 days prior to and 5 days during the behavioral tests. Behavioral assessment was performed in MWM. At the end of the behavioral test, blood samples and brain tissues were taken for the analysis of malondialdeyde (MDA), protein carbonyl and glutathione levels. During the training session, curcumin supplementation decreased latency to reach to the platform and the total distance traveled. During the probe trial, curcumin supplementation increased the number of platform crossings. In addition to the behavioral testing, biochemical results showed that MDA levels decreased in brain tissue by curcumin supplementation. It may be concluded that, curcumin supplementation improves cognitive functions by decreasing the lipid peroxidation in brain tissue of aged female rats.

Topics: Aging; Animals; Antioxidants; Behavior, Animal; Brain; Cognition; Curcumin; Disease Models, Animal; Female; Glutathione; Malondialdehyde; Maze Learning; Memory; Memory Disorders; Oxidative Stress; Protein Carbonylation; Rats; Rats, Wistar

A number of neuroprotective effects of curcumin have been demonstrated in recent years. However, whether curcumin exerts any beneficial effects on age-related impaired cognition and memory has not been well characterized; nor was there any detailed data on the molecular pathways activated by curcumin. The present study attempts to investigate the effects of curcumin on memory decline of aged mice with a focus upon the possible contribution of the neuronal nitric oxide synthase (nNOS)/nitric oxide (NO) pathway in the memory amelioration effect of curcumin. The results showed that chronic administration of curcumin (50mg/kg, i.p., 21 days) significantly ameliorated the memory acquisition ability of aged male mice in the novel object recognition and passive avoidance tasks. Immunoblotting revealed that chronic treatment of curcumin increased nNOS expression in the prefrontal cortex, amygdala and hippocampus, as well as the enhancement of nNOS activity and NO concentration. This enhancement was suppressed by pre-treatment with 7-nitroindazole (7-NI), a specific inhibitor of neuronal nitric oxide synthase (nNOS). Furthermore, inhibition of nNOS synthase by 7-NI also prevented the memory improvement effects of curcumin in aged mice. Taken together, the results of the present study suggest that the amelioration of memory deficits by curcumin in aged mice was mediated, at least in part, by activating the nNOS activity in specific brain regions. These findings reveal the therapeutic potential of curcumin as a preventive agent upon the deterioration of cognitive faculties.

Topics: Aging; Animals; Brain; Curcumin; Indazoles; Male; Memory Disorders; Mice; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase Type I

The comparative preventive effect of curcumin, memantine, and diclofenac on scopolamine-induced memory dysfunction was investigated in a controlled study. A group of male and female rats was treated with one of these compounds for 15 days, after which a single dosage of scopolamine was administered. The preventive activity of curcumin on memory dysfunction was higher than that of diclofenac or memantine, that was, however, administered at lower dosages. Gender differences were observed.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cholinergic Antagonists; Curcumin; Diclofenac; Excitatory Amino Acid Antagonists; Female; Male; Maze Learning; Memantine; Memory Disorders; Phytotherapy; Plant Extracts; Rats; Scopolamine; Sex Factors

The present study was designed to investigate the role of curcumin in chronic stress and chronic unpredictable stress-induced memory deficits and alteration of functional homeostasis in mice. Chronic stress was induced by immobilizing the animal for 2 h daily for 10 days, whereas chronic unpredictable stress was induced by employing a battery of stressors of variable magnitude and time for 10 days. Curcumin was administered to drug-treated mice prior to induction of stress. Body weight, adrenal gland weight, ulcer index and biochemical levels of glucose, creatine kinase, cholesterol, corticosterone, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were evaluated to assess stress-induced functional changes. Memory deficits were evaluated using the elevated plus maze (EPM) model. Chronic stress and chronic unpredictable stress significantly increased the levels of corticosterone, glucose and creatine kinase and decreased cholesterol levels. Moreover, chronic stress and chronic unpredictable stress resulted in severe memory deficits along with adrenal hypertrophy, weight loss and gastric ulceration. Chronic stress and chronic unpredictable stress also increased oxidative stress assessed in terms of increase in TBARS and decrease in GSH levels. Pretreatment with curcumin (25 and 50 mg/kg p.o.) attenuated chronic stress and chronic unpredictable stress-associated memory deficits, biochemical alterations, pathological outcomes and oxidative stress. It may be concluded that curcumin-mediated antioxidant actions and decrease in corticosterone secretion are responsible for its adaptogenic and memory restorative actions in chronic and chronic unpredictable stress.

Topics: Animals; Blood Glucose; Cholesterol; Corticosterone; Creatine Kinase; Curcumin; Female; Glutathione; Male; Memory Disorders; Mice; Stress, Physiological; Thiobarbituric Acid Reactive Substances

Reduced cognitive function is associated with Alzheimer's and Parkinson's diseases as well as brain trauma and ischemia. However, there are few compounds that enhance memory and are also orally active. We recently synthesized a pyrazole derivative of curcumin called CNB-001 that enhances the activity of Ca(2+)/calmodulin dependent protein kinase II (CaMKII). Since CaMKII plays a central role in long-term potentiation (LTP) and memory, it was asked if CNB-001 can facilitate the induction of LTP in rat hippocampal slices and enhance memory in a rat object recognition test. It is shown that CNB-001 enhances both LTP and memory.

Topics: Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cognition Disorders; Curcumin; Hippocampus; Long-Term Potentiation; Male; Memory; Memory Disorders; Nerve Degeneration; Neurodegenerative Diseases; Neuroprotective Agents; Neuropsychological Tests; Nootropic Agents; Organ Culture Techniques; Pyrazoles; Rats; Rats, Wistar; Recognition, Psychology; Treatment Outcome

The aim of the present study is to investigate the effect of curcumin on cerebral blood flow (CBF), memory impairment, oxidative stress and cholinergic dysfunction in intracerebral (IC) streptozotocin (STZ) induced memory impairment in mice.. Memory impairment was induced by STZ (0.5mg/kg, IC) administered twice with an interval of 48h in mice. Memory function was assessed by Morris water maze and passive avoidance test. CBF was measured by Laser Doppler Flowmetry (LDF). To study the preventive effect, curcumin (10, 20 and 50mg/kg, PO) was administered for 21days starting from the first dose of STZ. In another set of experiment, curcumin was administered for 7days from 19th day after confirming STZ induced dementia to observe its therapeutic effect. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain on day 21.. The major finding of this study is that STZ (IC) caused a significant reduction in CBF along with memory impairment, cholinergic dysfunction and enhanced oxidative stress. Curcumin dose dependently improved CBF in STZ treated mice together with amelioration of memory impairment both in preventive and therapeutic manner.. The present study clearly demonstrates the beneficial effects of curcumin, the dietary staple of India, on CBF, memory and oxidative stress which can be exploited for dementia associated with age related vascular and neurodegenerative disorders.

Topics: Acetylcholinesterase; Animals; Avoidance Learning; Blood Glucose; Brain; Cerebrovascular Circulation; Curcumin; Disease Models, Animal; Glutathione; Injections, Intraventricular; Laser-Doppler Flowmetry; Male; Malondialdehyde; Maze Learning; Memory Disorders; Mice; Motor Activity; Neuroprotective Agents; Oxidative Stress; Reactive Oxygen Species; Streptozocin

Curcumin, the principal curcuminoid of turmeric, exhibits beneficial role in several neurodegenerative disorders such as dementia of Alzheimer type. Recent evidences suggest the involvement of brain insulin receptors (IRs) in the pathophysiology of dementia disorders. Therefore, the present study was undertaken to investigate the effect of curcumin on memory functions, brain IRs, acetylcholinesterase (AChE) activity and oxidative stress in intracerebroventricular (ICV) administered streptozotocin (STZ) induced dementia in rats. Rats were injected with STZ (3 mg/kg, ICV) bilaterally twice, on day 1 and 3 and curcumin (200 mg/kg, po) was administered in pre- and post-treatment schedules. STZ (ICV) treated group had shown memory deficit as indicated by no significant decrease in latency time in Morris water maze test and significant decrease in IR protein level in both hippocampus and cerebral cortex. Pre- and post-treatment of curcumin in STZ (ICV) treated rats significantly restored the memory deficit and IR protein level in both the regions. Furthermore, STZ (ICV) resulted into enhanced AChE activity in hippocampus and cerebral cortex which was normalized by curcumin pre- and post-treatment. An increase in MDA level and decrease in GSH level were obtained in both hippocampus and cerebral cortex in STZ treated group, indicating state of oxidative stress, which was also attenuated by pre- and post-treatment of curcumin. The results suggest that besides the anticholinesterase and antioxidant activity, effect on brain IR may also be an important factor for protective effect of curcumin against STZ induced dementia model.

Topics: Animals; Brain; Curcumin; Dementia; Disease Models, Animal; Male; Memory; Memory Disorders; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Streptozocin

The present study was undertaken to investigate the possible mechanism of curcumin-mediated beneficial effects in memory deficits associated with experimental dementia. Dementia was induced in Swiss albino mice by administering streptozotocin (3 mg kg(-1)) intracerebroventricularly on first and third day. Morris water maze test was employed to assess learning and memory of the animals. Biochemical analysis of brain homogenate was performed to assess brain acetyl cholinesterase (AChE) activity and total oxidative stress. Streptozotocin (STZ) produced a significant decrease in water maze performance of mice indicative of impairment in spatial reference memory. Curcumin (20 mg/kg p.o. daily for 14 days) successfully attenuated STZ-induced memory deficits. Higher levels of brain AChE activity and oxidative stress were observed in STZ-treated animals, which were significantly attenuated by curcumin. Furthermore, the noted beneficial effect of curcumin on STZ-induced dementia was significantly abolished by pretreatment with PPAR-gamma receptor antagonist bisphenol-A-diglycidyl ether, i.e., BADGE (30 mg/kg intraperitoneally (i.p.)). It may be concluded that the beneficial effects of curcumin are mediated through the activation of PPAR-gamma receptors.

Topics: Acetylcholinesterase; Animals; Benzhydryl Compounds; Brain; Curcumin; Dementia; Disease Models, Animal; Epoxy Compounds; Female; Male; Memory Disorders; Mice; Oxidative Stress; PPAR gamma; Streptozocin

The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.

Topics: Animals; Anticonvulsants; Antioxidants; Avoidance Learning; Brain; Carbamazepine; Cognition Disorders; Curcumin; Drug Interactions; Lipid Peroxidation; Male; Malondialdehyde; Maze Learning; Memory Disorders; Oxidative Stress; Phenobarbital; Rats; Rats, Wistar

Human immunodeficiency virus-1 (HIV-1)-associated dementia (HAD) is a significant consequence of HIV infection. Although highly active antiretroviral therapy (HAART) has dramatically decreased HIV-1 load in acquired immune deficiency syndrome (AIDS) patients, HAART does not completely protect against the development of HAD, therefore novel strategies for the prevention and treatment are urgently needed. In this study, we chose curcumin which has a neuroprotective role and tested the effect against neuron damage induced by HIV-1gp120 V3 loop peptide.. Rats were given 150 ng gp120 V3 peptide by intracerebroventricular (ICV) infusion for 3 days to establish the cognitive dysfunction model. After recovery from the surgery, the rats in treatment groups were given curcumin by intragastric infusion for 2 weeks. Subsequently, we used the Morris water maze test, long-term potentiation (LTP) recording, biochemical measurement of oxidative damage, Nissl staining, and BDNF immunostaining to evaluate the neuropathological changes and the effect of curcumin on rats.. Our results documented that the gp120 V3 peptide induced impairment of spatial learning and memory, inhibited LTP in the CA1 region of the hippocampus, and mediated oxidative stress and neuronal injury. These impairments were ameliorated by intragastric infusion of curcumin.. These results suggested that dietary supplementation of curcumin may be a potential therapeutic strategy for the treatment and/or prevention of HAD.

Topics: AIDS Dementia Complex; Animals; Brain-Derived Neurotrophic Factor; Curcumin; Electrophysiology; Excitatory Postsynaptic Potentials; Female; Hippocampus; HIV Envelope Protein gp120; Hydroxyl Radical; Immunohistochemistry; Injections, Intraventricular; Lipid Peroxidation; Long-Term Potentiation; Male; Malondialdehyde; Maze Learning; Memory Disorders; Neurons; Oxidative Stress; Peptide Fragments; Rats; Rats, Sprague-Dawley; Stereotaxic Techniques; Superoxide Dismutase

Chronic stress occurs in everyday life and induces impaired spatial cognition, neuroendocrine and plasticity abnormalities. A potential therapeutic for these stress related disturbances is curcumin, derived from the curry spice turmeric. Previously we demonstrated that curcumin reversed the chronic stress-induced behavioral deficits in escape from an aversive stimulus, however the mechanism behind its beneficial effects on stress-induced learning defects and associated pathologies are unknown. This study investigated the effects of curcumin on restraint stress-induced spatial learning and memory dysfunction in a water maze task and on measures related neuroendocrine and plasticity changes. The results showed that memory deficits were reversed with curcumin in a dose dependent manner, as were stress-induced increases in serum corticosterone levels. These effects were similar to positive antidepressant imipramine. Additionally, curcumin prevented adverse changes in the dendritic morphology of CA3 pyramidal neurons in the hippocampus, as assessed by the changes in branch points and dendritic length. In primary hippocampal neurons it was shown that curcumin or imipramine protected hippocampal neurons against corticosterone-induced toxicity. Furthermore, the portion of calcium/calmodulin kinase II (CaMKII) that is activated (phosphorylated CaMKII, pCaMKII), and the glutamate receptor sub-type (NMDA(2B)) expressions were increased in the presence of corticosterone. These effects were also blocked by curcumin or imipramine treatment. Thus, curcumin may be an effective therapeutic for learning and memory disturbances as was seen within these stress models, and its neuroprotective effect was mediated in part by normalizing the corticosterone response, resulting in down-regulating of the pCaMKII and glutamate receptor levels.

Topics: Animals; Antidepressive Agents, Tricyclic; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cells, Cultured; Cognition Disorders; Corticosterone; Curcumin; Hippocampus; Imipramine; Learning Disabilities; Male; Maze Learning; Memory Disorders; Neuronal Plasticity; Neuroprotective Agents; Pyramidal Cells; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Space Perception; Stress, Psychological

Aluminium is a potent neurotoxin and has been associated with Alzheimer's disease (AD) causality for decades. Prolonged aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo. Current treatment modalities for AD provide only symptomatic relief thus necessitating the development of new drugs with fewer side effects. The aim of the study was to demonstrate the protective effect of chronic curcumin administration against aluminium-induced cognitive dysfunction and oxidative damage in rats. Aluminium chloride (100 mg/kg, p.o.) was administered to rats daily for 6 weeks. Rats were concomitantly treated with curcumin (per se; 30 and 60 mg/kg, p.o.) daily for a period of 6 weeks. On the 21st and 42nd day of the study behavioral studies to evaluate memory (Morris water maze and elevated plus maze task paradigms) and locomotion (photoactometer) were done. The rats were sacrificed on 43rd day following the last behavioral test and various biochemical tests were performed to assess the extent of oxidative damage. Chronic aluminium chloride administration resulted in poor retention of memory in Morris water maze, elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant increase in the acetylcholinesterase activity and aluminium concentration in aluminium treated rats. Chronic administration of curcumin significantly improved memory retention in both tasks, attenuated oxidative damage, acetylcholinesterase activity and aluminium concentration in aluminium treated rats (P<0.05). Curcumin has neuroprotective effects against aluminium-induced cognitive dysfunction and oxidative damage.

Topics: Acetylcholinesterase; Aluminum; Aluminum Chloride; Aluminum Compounds; Animals; Brain; Chlorides; Curcumin; Dose-Response Relationship, Drug; Glutathione; Lipid Peroxidation; Locomotion; Male; Maze Learning; Memory Disorders; Neuroprotective Agents; Neuropsychological Tests; Nitrites; Oxidation-Reduction; Rats; Rats, Wistar

To explore the effect and mechanisms of curcumin on learning and memory dysfunction induced by HIV-1 enveloped protein gp120.. The SD rats were treated with gp120 by intracerebroventricular (ICV) infusion imitating the HIV-1 associated dementia (HAD) animal model. Subsequently, we applied the water maze test to evaluate the effect of gp120 on the learning and memory dysfunction in rats. The SD rats were divided into six groups: control group, sham group, model group, low dose curcumin group, middle dose curcumin group and high dose curcumin group. Except control and sham group, the others four groups received slowly 5 microL/d gp120 which dissolved in artificial cerebrospinal fluid (ACSF) for 3 days. Since the fourth day, the rats of low, middle, high dose curcumin groups were treated with 50 mg/(kg.d), 100 mg/(kg.d), 200 mg/(kg.d) curcumin, respectively. The others groups were treated with redistilled water. The treatment lasted for 14 days. Subsequently, the water maze test and NMDA2BR immunohistochemical staining were applied to evaluate the effect of curcumin on the rats.. The rats were treated with gp120 50 ng/d by ICV infusion for 3 days can imitate the HAD animal model. The Morris water maze (MWM) test showed that the rats in model group had longer escape latencies compared with those in control group (P<0.05) and that rats in low, middle, high dose curcumin groups had shorter escape latencies compared with those in model group (P<0.05), and low dose curcumin group was better than the other two groups (P<0.05). Immunohistochemical staining showed that the expressions of NMDA2BR in model group decreased compared with the control groups (P<0.01), while the expressions of NMDA2BR in low, middle and high dose curcumin groups increased compared with the model groups.. The SD rats were treated with gp120 by ICV infusion imitating the HAD animal model. The curcumin can improve the learning and memory dysfunction induced by gp120, the mechanism may be related to against the downregulation the expression of NMDA2BR.

Topics: AIDS Dementia Complex; Animals; Curcumin; Female; HIV Envelope Protein gp120; Immunohistochemistry; Male; Maze Learning; Memory Disorders; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate

This study investigated the neuroprotective effects of the curcuminoids against lead-induced neurotoxicity. The results show that lead significantly increases lipid peroxidation and reduces the viability of primary hippocampal neurons in culture. This lead-induced toxicity was significantly curtailed by the co-incubation of the neurons with the curcuminoids. In a whole animal experiment, rats were trained in a water maze and thereafter dosed with lead and/or curcumin (CURC), demethoxycurcumin (DMC), or bisdemethoxycurcumin (BDMC) for 5 days. Animals treated with curcumin and demethoxycurcumin but not bisdemethoxycurcumin had more glutathione and less oxidized proteins in the hippocampus than those treated with lead alone. These animals also had faster escape latencies when compared to the Pb-treated animals indicating that CURC- and DMC-treated animals retain the spatial reference memory. The findings of this study indicate that curcumin, a well-established dietary antioxidant, is capable of playing a major role against heavy metal-induced neurotoxicity and has neuroprotective properties.

Topics: Animals; Curcumin; Diarylheptanoids; Glutathione; Hippocampus; Lead; Male; Memory Disorders; Nerve Tissue Proteins; Oxidation-Reduction; Rats; Rats, Wistar