stilbenes and Memory-Disorders

We assessed the clinical utility of β-amyloid (Aβ) imaging with (18)F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time.. 45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥ 1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <-1.5.. At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB-, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB- developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB- had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB-.. (18)F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline.. NCT01138111.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Cognitive Dysfunction; Disease Progression; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Memory Disorders; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Stilbenes

Cognitive impairment is the main clinical manifestation of Alzheimer's disease (AD), and amyloid-β (Aβ) deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains. This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside (TSG) on cognitive function in APP/PS1 mice during long-term administration. Here, we treated APP/PS1 model mice of AD with different doses of TSG (50 mg/kg and 100 mg/kg) for 5 to 17 months by gavage, and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests, and investigated the possible mechanisms by immunohistochemistry and Western blotting. Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test. Furthermore, Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique. Finally, Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβ plaque deposition in the cortex and hippocampus of mice. These results reveal the beneficial effects of TSG in APP/PS1-AD mice, which may be associated with the reduction of Aβ deposits in the brain.

Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Cognitive Dysfunction; Glucosides; Hippocampus; Memory Disorders; Mice, Transgenic; Peptide Fragments; Presenilin-1; Stilbenes

Subjective cognitive decline (SCD) may herald the first symptoms of Alzheimer's disease (AD) whereas individuals with beta-amyloid (Aβ) deposition are regarded as a high-risk group for AD. Recently, amyloid positron emission tomography (PET) studies have demonstrated clinical and cognitive feature differences between Aβ-positive and negative SCD, but details of their differences remain unclear. We aimed to investigate the relationships among Aβ deposition, clinical, and cognitive features in patients with SCD.. Forty-two patients with SCD (22 women, 74.5 ± 4.7 years) were examined using fluorine-18 florbetaben PET and were divided into Aβ-positive (n = 10) and negative (n = 32) groups. We compared cognitive and psychological outcomes, and single photon emission computed tomography (SPECT) imaging data between the two groups. In addition, a linear regression analysis was performed to assess relationships between the severity of SCD and neuropsychological tests, affective scores, and demographic factors.. The rate of score changes from the immediate recall to delayed recall in the logical memory subtest of the Wechsler's Memory Scale Revised were different between the groups (P = 0.04). However, the binary logistic regression analysis showed no significant differences between the two. In addition, the severity of SCD was significantly strong in women (P = 0.002). Furthermore, within the Aβ-negative group, subjective memory loss correlated with word fluency category score (P = 0.023) and apathy scale (P = 0.037).. No significant differences were observed between Aβ-positive and -negative SCD on any of the neuropsychological measures, clinical measures, or SPECT imaging. Further, the severity of SCD was not predicted by the symptoms of anxiety, depression, or neuropsychological examination.

Topics: Aged; Aged, 80 and over; Amyloid beta-Peptides; Aniline Compounds; Cerebrovascular Circulation; Cognitive Dysfunction; Diagnostic Self Evaluation; Female; Humans; Male; Memory Disorders; Positron-Emission Tomography; Severity of Illness Index; Stilbenes; Tomography, Emission-Computed, Single-Photon

trans-Resveratrol, a natural polyphenol enriched in grape seed and skin, has been extensively investigated for its antioxidant, anti-inflammatory and anti-psychiatric properties. The present study examined the effects of trans-resveratrol on ameliorating anxiety-like behaviors and fear memory deficits induced by time-dependent sensitization (TDS) procedure, which is a classical animal model for mimicking posttraumatic stress disorder (PTSD). The results suggested that trans-resveratrol at doses of 10, 20 and 40 mg/kg (via gavage, i.g.) reversed TDS-induced decreases in the percentage of time spent in the center of arena, the open arm entries and time spent in the open arms in the open field and elevated plus maze tests. It also decreased the percentage of freezing time in the contextual fear paradigm that was increased in TDS treated rats. Further study suggested that TDS-induced abnormality in the limbic hypothalamus-pituitary-adrenal gland (L-HPA) axis was reversed by trans-resveratrol, i.e. it reversed increased adrenal gland index and corticotropin-releasing factor (CRF) levels, and rescued the differential expression of glucocorticoid receptor (GR) in the hypothalamus, hippocampus and amygdala. Neurobiological studies suggested that trans-resveratrol increased phosphorylation of cAMP response element binding protein (pCREB) and brain derived neurotrophic factor (BDNF) levels, which were decreased in rats subjected to TDS. These results provide compelling evidence that trans-resveratrol protects neurons against PTSD-like stress insults by regulation of L-HPA axis function and activation of downstream neuroprotective molecules, such as pCREB and BDNF expression.

Topics: Adrenal Glands; Analysis of Variance; Animals; Antioxidants; Anxiety; Brain-Derived Neurotrophic Factor; Corticotropin-Releasing Hormone; CREB-Binding Protein; Disease Models, Animal; Exploratory Behavior; Fear; Male; Maze Learning; Memory Disorders; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Stress Disorders, Post-Traumatic

Because resveratrol (RSV) has been shown to improve learning and memory, so we investigated the potential benefit of RSV on learning and memory deficits in juvenile mice fed with a HC diet and explored the molecular mechanisms underlying this process.. Six-week-old C57BL/6J mice were divided into three different diet groups: control, HC diet, and HC + RSV diet. Serum insulin and insulin-like growth factor 1 (IGF-1) levels were measured using enzyme-linked immunosorbent assays. Protein expression was examined by immunohistochemistry and western blotting.. Administration of RSV daily (30 mg/kg) prevented the HC diet-induced increase in juvenile animal body weight but did not improve any other physiological conditions, including fasting blood glucose and serum cholesterol, triglyceride, insulin, and IGF-1 levels. However, RSV did prevent learning and memory deficits in the HC group. Peroxisome proliferator-activated receptor gamma (PPARγ) was downregulated in the CA1 region of the hippocampus in both the HC and HC + RSV groups, but the reduction was significantly greater in the HC + RSV group (P < .01 compared with the HC group). Moreover, although the HC diet reduced the number of p16-positive neurons, the HC + RSV diet significantly upregulated p16 expression in the CA1 region of the hippocampus (P < .01 compared with the HC group).. RSV protected against learning and memory impairments in juvenile animals fed with a HC diet, possibly via upregulation of p16 or downregulation of PPARγ in the hippocampal CA1 region.

Topics: Animals; Biomarkers; Body Weight; CA1 Region, Hippocampal; Diet, High-Fat; Female; Learning Disabilities; Male; Maze Learning; Memory; Memory Disorders; Mice, Inbred C57BL; Neuroprotection; Nootropic Agents; Random Allocation; Resveratrol; Sirtuin 1; Stilbenes

β-amyloid (Aβ) deposition is considered partially responsible for cognitive dysfunction in Alzheimer's disease (AD). Recently, resveratrol has been reported to play a potential role as a neuroprotective biofactor by modulating Aβ pathomechanisms, including through anti-neuronal apoptotic, anti-oxidative stress, and anti-neuroinflammatory effects. In addition, SIRT1 has been demonstrated to modulate learning and memory function by regulating the expression of cAMP response binding protein (CREB), which involves in modulating the expression of SIRT1. However, whether resveratrol can alleviate Aβ-induced cognitive dysfunction, whether SIRT1 expression and CREB phosphorylation in the hippocampus are affected by Aβ, and whether resveratrol influences these effects remain unknown. In the present study, we used a hippocampal injection model in rats to investigate the effects of resveratrol on Aβ

Topics: Amyloid beta-Peptides; Animals; Blotting, Western; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Hippocampus; Learning Disabilities; Long-Term Potentiation; Male; Memory Disorders; Neuroprotective Agents; Nootropic Agents; Peptide Fragments; Phosphorylation; Random Allocation; Rats, Sprague-Dawley; Resveratrol; Sirtuin 1; Spatial Learning; Spatial Memory; Stilbenes; Time Factors

The aim of this study was to investigate the role of resveratrol on subacute systemic inflammation-induced dysfunction of cognitive memory in mice and its underlying mechanism. Male ICR mice were trained in a water maze for four days of acquisition training and one day of probe trial. Subacute treatment with lipopolysaccharide (LPS) (1 mg/kg) by intraperitoneal injection for 5 days was used to establish a systemic inflammatory model. All mice were sacrificed after probe testing, then the expression of glial fibrillary acidic protein (GFAP), synaptophysin, and sirtuin1 (SIRT1) in hippocampi were determined using immunohistochemistry or western blot analysis. Morris water maze tests indicated that hippocampus-dependent spatial learning and memory were impaired in LPS-treated group. Resveratrol attenuated LPS-induced memory deficit in dose-dependent manner. Immunohistochemistry and western blot analysis revealed that LPS increased hippocampal GFAP expression and inhibited synaptophysin expression, which were prevented by resveratrol treatment. Treatment with LPS declined the SIRT1 protein expression in the hippocampus, which could be prevented by resveratrol. The protective effect of resveratrol could be abolished by a specific SIRT1 inhibitor. Our findings add new experimental data for potential therapeutic effects of resveratrol in the brain in a model of subacute systemic inflammation-induced astrocyte activation, synaptic alteration and cognitive decline.

Topics: Animals; Astrocytes; Blotting, Western; Glial Fibrillary Acidic Protein; Hippocampus; Hyperalgesia; Immunohistochemistry; Inflammation; Lipopolysaccharides; Male; Maze Learning; Memory Disorders; Mice, Inbred ICR; Microglia; Models, Biological; Resveratrol; Sirtuin 1; Spatial Memory; Stilbenes; Synaptophysin

This study was intended to investigate whether treatment with resveratrol and melatonin alone or in combination can exert neurorestorative effects in a rat model of vascular dementia.. Briefly, male Wistar rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) by surgery. After 4 weeks, the cognitive deficits were assessed using the Morris water maze and novel object recognition tests. The biochemical parameters of oxidative stress and inflammation were also assessed.. Rats in the BCCAO group showed cognitive deficits, accompanied by oxidonitrosative stress, neuroinflammation, and a reduction in brain-derived neurotrophic factor (BDNF) in the hippocampus region. Moreover, the acetylcholinesterase activity in the hippocampus was found to be increased in the BCCAO group compared to the sham group. The 4-week treatment with melatonin (10 mg/kg) and resveratrol (20 mg/kg) alone and in combination (melatonin 5 mg/kg and reseveratrol 10 mg/kg) caused a significant improvement in the cognitive deficits induced by BCCAO, accompanied by a reversal of oxidonitrosative stress, neuroinflammation, and BDNF depletion in the hippocampus region. Additionally, the treatment with melatonin and resveratrol significantly decreased acetylcholinesterase activity compared to in the BCCAO group. Melatonin and resveratrol ameliorated the BDNF expression of hippocampal protein.. These results emphasize that coadministration of melatonin and resveratrol can be beneficial in BCCAO-induced vascular dementia through changes in BDNF expressions.

Topics: Animals; Antioxidants; Brain-Derived Neurotrophic Factor; Dementia, Vascular; Disease Models, Animal; Drug Therapy, Combination; Glutathione; Hippocampus; Interleukin-1beta; Male; Malondialdehyde; Maze Learning; Melatonin; Memory Disorders; Models, Molecular; Rats; Rats, Wistar; Recognition, Psychology; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha

Dementia is the most prevalent neurological disease in aged people. Chronic cerebral hypoperfusion (CCH) is one of the causes of vascular dementia (VaD) and is also an etiological factor for Alzheimer's disease (AD). However, effective therapy for those two diseases is still missing. Resveratrol is a polyphenol produced by plants that have multiple biological functions, such as increased life span and delay in the onset of diseases associated with aging. It is known supplement with resveratrol could exert neuroprotection against multiple injury factors induced neuronal death and degeneration, as well as the cognitive decline of CCH rat model.. The morris water maze was used to evaluate the learning and memory, electrophysiological recording was used to detect the synaptic plasticity, the Golgi staining was used to examine the change of dendritic spines, the western blot was used to detect the proteins levels.. We reported that resveratrol pretreatment effectively restore the synaptic plasticity in CCH rats both functional and structural. We also found that the PKA-CREB activation may be a major player in resveratrol-mediated neuroprotection in CCH model.. Our data provide the mechanistic evidence for the neuroprotective effects of resveratrol in vascular dementia.

Topics: Animals; Carotid Stenosis; Cerebrovascular Circulation; Chronic Disease; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Dementia, Vascular; Dendritic Spines; Dentate Gyrus; Enzyme Activation; Hypoxia-Ischemia, Brain; Learning Disabilities; Long-Term Potentiation; Male; Maze Learning; Memory Disorders; Nerve Tissue Proteins; Neuroprotective Agents; Random Allocation; Rats; Rats, Wistar; Resveratrol; Stilbenes

Aberrant gene expression within the hippocampus has recently been implicated in the pathogenesis of obesity-induced memory impairment. Whether a dysregulation of epigenetic modifications mediates this disruption in gene transcription has yet to be established. Here we report evidence of obesity-induced alterations in DNA methylation of memory-associated genes, including Sirtuin 1 (Sirt1), within the hippocampus, and thus offer a novel mechanism by which SIRT1 expression within the hippocampus is suppressed during obesity. Forebrain neuron-specific Sirt1 knock-out closely recapitulated the memory deficits exhibited by obese mice, consistent with the hypothesis that the high-fat diet-mediated reduction of hippocampal SIRT1 could be responsible for obesity-linked memory impairment. Obese mice fed a diet supplemented with the SIRT1-activating molecule resveratrol exhibited increased hippocampal SIRT1 activity and preserved hippocampus-dependent memory, further strengthening this conclusion. Thus, our findings suggest that the memory-impairing effects of diet-induced obesity may potentially be mediated by neuroepigenetic dysregulation of SIRT1 within the hippocampus.. Previous studies have implicated transcriptional dysregulation within the hippocampus as being a relevant pathological concomitant of obesity-induced memory impairment, yet a deeper understanding of the basis for, and etiological significance of, transcriptional dysregulation in this context is lacking. Here we present the first evidence of epigenetic dysregulation (i.e., altered DNA methylation and hydroxymethylation) of memory-related genes, including Sirt1, within the hippocampus of obese mice. Furthermore, experiments using transgenic and pharmacological approaches strongly implicate reduced hippocampal SIRT1 as being a principal pathogenic mediator of obesity-induced memory impairment. This paper offers a novel working model that may serve as a conceptual basis for the development of therapeutic interventions for obesity-induced memory impairment.

Topics: Animals; Antioxidants; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; DNA Methylation; Excitatory Postsynaptic Potentials; Exploratory Behavior; Gene Expression Regulation; Hippocampus; Insulin; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Obesity; Prosencephalon; Recognition, Psychology; Resveratrol; Sirtuin 1; Spatial Memory; Stilbenes; Time Factors

Long-term intermittent hypoxia (IH) is a characteristic hallmark of obstructive sleep apnea (OSA) and causes most of the neurological aspects of OSA, such as spatial memory and learning deficits. These deficits are accompanied by an increase in oxidative stress and inflammation in brain areas involved in cognition, such as the hippocampus, particularly in children. Resveratrol is a natural polyphenolic compound with potent antioxidant, anti-inflammatory and neuroprotective properties.. The aim of this work is to study the possible protective effect of resveratrol against IH-induced neurobehavioral deficits and to investigate the possible mechanism of this protective effect in the young rat model of OSA.. The effect of resveratrol (5 and 10mg/kg, orally) on anxiety, spatial memory and learning deficits in young rats exposed to IH for 6 weeks and the corresponding biochemical changes were studied.. Resveratrol attenuated IH-induced anxiety and spatial memory deficits, as indicated by the elevated plus maze and Morris water maze tests, respectively, in a dose-dependent manner. In addition, resveratrol antagonized IH-induced increases in hippocampal glutamate, TBARS and 8-OHdG levels and p47Phox expression and decreases in GSH levels and GSH-Px activity in the hippocampus of IH-exposed young rats.. Resveratrol ameliorates IH-induced anxiety and spatial learning deficits through multiple beneficial effects on hippocampal oxidative pathways that involve decreased expression of the p47Phox subunit of NADPH oxidase. Hence, the potential therapeutic role of resveratrol in OSA may be utilized in the near future and deserves further exploration.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Deoxyguanosine; Disease Models, Animal; DNA Damage; Dose-Response Relationship, Drug; Glutamic Acid; Glutathione; Glutathione Reductase; Hemoglobins; Hippocampus; Hypoxia; Male; Maze Learning; Memory Disorders; NADPH Oxidases; Neuroprotective Agents; Rats; Rats, Wistar; Reaction Time; Resveratrol; Stilbenes; Thiobarbituric Acid Reactive Substances

Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Aβ) are known to involve cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Activation of cAMP and/or cGMP activities can improve memory performance and decrease the neuroinflammation and apoptosis. However, it remains unknown whether the memory enhancing effect of resveratrol on AD associated cognitive disorders is related to the inhibition of phosphodiesterase 4 (PDE4) subtypes and subsequent increases in intracellular cAMP and/or cGMP activities. This study investigated the effect of resveratrol on Aβ1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Aβ1-42 into bilateral CA1 subregions displayed learning and memory impairment, as evidenced by reduced memory acquisition and retrieval in the water maze and retention in the passive avoidance tasks; it was also significant that neuroinflammatory and pro-apoptotic factors were increased in Aβ1-42-treated mice. Aβ1-42-treated mice also increased in PDE4A, 4B and 4D expression, and decreased in PKA level. However, PKA inhibitor H89, but not PKG inhibitor KT5823, prevented resveratrol's effects on these parameters. Resveratrol also reversed Aβ1-42-induced decreases in phosphorylated cAMP response-element binding protein (pCREB), brain derived neurotrophic factor (BDNF) and anti-apoptotic factor BCl-2 expression, which were reversed by H89. These findings suggest that resveratrol reversing Aβ-induced learning and memory disorder may involve the regulation of neuronal inflammation and apoptosis via PDE4 subtypes related cAMP-CREB-BDNF signaling.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Apoptosis; Cyclic Nucleotide Phosphodiesterases, Type 4; Disease Models, Animal; Male; Memory Disorders; Mice; Mice, Inbred ICR; Peptide Fragments; Phosphodiesterase 4 Inhibitors; Resveratrol; Signal Transduction; Stilbenes

Neonatal hypoxic-ischemic (HI) brain damage causes acute mortality and morbidity in newborns and long-term neurological disorders in the survivors. Pterostilbene (PTE) is a natural compound possessing various biological and pharmacological activities. In the present study, we aimed to investigate the effect of PTE on neonatal HI brain damagein P7 rat model and to explore the possible mechanisms. Neonatal HI brain damage was induced in rat pups (P7). Prior to the induction of HI injury, PTE was injected with or without zinc protoporphyrin IX (ZnPP), an inhibitor of heme oxygenase-1 (HO-1). ZnPP was used to test whether abnormal changes of HO-1 expression were involved in the effect of PTE. The results showed that PTE exhibited excellent neuroprotective effects against neonatal HI brain injury, as evidenced by the decrease of brain infarct volume, brain edema, neurological score, and improvement in motor coordination motor deficit and working memory deficit. PTE pretreatment decreased the expression of several proinflammatory cytokines, including TNFα, IL-1β, IL-6, and key transcription factor p65 NF-κB, and reduced the number of TUNEL-stained neurons, indicating the inhibition of inflammation and programmed cell death. Moreover, PTE pretreatment decreased thiobarbituric acid reactive substances content, increased superoxide dismutase activity and decreased reactive oxygen species level, indicating that PTE played an important antioxidant role. Furthermore, ZnPP was able to inhibit PTE-induced suppression of oxidative stress, programmed cell death, inflammation and brain damage. In conclusion, PTE pretreatment prevented HI-induced brain injury in newborns through HO-1-mediated reduction of oxidative stress, programmed cell death, and inflammation, and final improvement of histological and functional injury. Overall, the data that obtained in rat model provide novel insights into the pathogenesis of neonatal HI brain injury and may be translational to human clinical intervention for HI-associated brain injury in newborns.

Topics: Animals; Animals, Newborn; Brain; Brain Edema; Brain Injuries; Cell Death; Cytokines; Disease Models, Animal; Enzyme Inhibitors; Female; Gait Disorders, Neurologic; Heme Oxygenase (Decyclizing); Hypoxia-Ischemia, Brain; Male; Memory Disorders; Neuroprotective Agents; Oxidative Stress; Protoporphyrins; Psychomotor Disorders; Rats; Stilbenes; Up-Regulation

A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation.

Topics: Amygdala; Animals; Anti-Inflammatory Agents; Brain-Derived Neurotrophic Factor; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Emotions; Hippocampus; Injections, Intraperitoneal; Interleukin-1beta; Male; Memory Disorders; Neuroprotective Agents; Proto-Oncogene Proteins c-fos; Rats, Wistar; Resveratrol; Spatial Learning; Spatial Memory; Stilbenes; Stress, Psychological; Tumor Necrosis Factor-alpha; Uncertainty

Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.

Topics: Aging; Animals; Astrocytes; CD11b Antigen; Cells, Cultured; Doublecortin Domain Proteins; Glial Fibrillary Acidic Protein; Hippocampus; Male; Maze Learning; Memory; Memory Disorders; Microtubule-Associated Proteins; Microvessels; Mood Disorders; Neurogenesis; Neuroglia; Neuropeptides; Rats; Rats, Inbred F344; Resveratrol; Stilbenes

Memory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood-brain barrier, we tested EH-201 (2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury.. The effects of EH-201 were investigated in astrocytes and PC12 neuronal-like cells. In vivo, we used sleep-deprived (SD) mice as a stress model, amyloid-β (Aβ)-injected mice as a physiological ageing model and kainic acid (KA)-injected mice as a brain damage model to assess the therapeutic effects of EH-201.. EH-201 induced expression of erythropoietin, PPAR-γ coactivator 1α (PGC-1α) and haemoglobin in astrocytes and PC12 neuronal-like cells. In vivo, EH-201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH-201 in their diet, levels of erythropoietin, PGC-1α and haemoglobin were increased. The induction of endogenous erythropoietin in neuronal cells by inducers such as EH-201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury.

Topics: Animals; Astrocytes; Cells, Cultured; Disease Models, Animal; Erythropoietin; Female; Glucosides; Hemoglobins; Hydrogen Peroxide; Kainic Acid; Male; Memory Disorders; Mice, Inbred C57BL; Mitochondria; Neuroprotective Agents; PC12 Cells; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Rats; Reactive Oxygen Species; Stilbenes; Succinate Dehydrogenase; Transcription Factors

The major purpose of this study was to investigate the effect of resveratrol (RES) on the spatial learning and memory ability in subclinical hypothyroidism (SCH) rat model and the potential mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization and the activity of hypothalamus-pituitary-thyroid (HPT) axis was detected. The spatial learning and memory ability was tested using Morris water maze (MWM) and Y-maze. The protein expressions of synaptotagmin-1 (syt-1) and brain-derived neurotrophic factor (BDNF) in the hippocampus were measured via western blot. The results showed that SCH rat model was successfully duplicated. The SCH rats showed impaired learning and memory in the behavioral tests. However, these changes were reversed by the treatment of RES (15mg/kg) and levothyroxine (LT4). Moreover, RES treated rats exhibited reduced plasma TSH level and hypothalamic thyrotropin releasing hormone (TRH) mRNA expression, which suggested that the imbalance of HPT axis in the SCH rats could be reversed by RES treatment. Furthermore, RES treatment up-regulated the protein levels of syt-1 and BDNF in hippocampus. These findings indicated an amelioration effect of RES on the spatial learning and memory in the SCH rats, the mechanism of which might be involved with its ability of modifying the hyperactive HPT axis and up-regulating the hippocampal hypo-expression of syt-1 and BDNF.

Topics: Animals; Antioxidants; Asymptomatic Diseases; Behavior, Animal; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Hippocampus; Hormone Replacement Therapy; Hypothyroidism; Learning Disabilities; Male; Maze Learning; Memory Disorders; Nerve Tissue Proteins; Neurons; Nootropic Agents; Random Allocation; Rats, Sprague-Dawley; Resveratrol; Spatial Learning; Stilbenes; Synaptotagmin I; Thyroxine

To investigate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) on the memory and movement functions and its mechanisms related to synapses and α-synuclein in aged mice.. The memory ability of mice was detected by step-through passive avoidance task. The movement function was measured by the pole test and rotarod test. Transmission electron microscopy was used to observe the synaptic ultrastructure. Western blotting was applied to measure the expression of synapse-related proteins and α-synuclein.. Intragastrical administration of TSG for 3 months significantly improved the memory and movement functions in aged mice. TSG treatment obviously protected the synaptic ultrastructure and increased the number of synaptic connections in the hippocampal CA1 region and striatum; enhanced the expression of synaptophysin, phosphorylated synapsin I and postsynaptic density protein 95 (PSD95), elevated phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMKII) expression, and inhibited the overexpression and aggregation of α-synuclein in the hippocampus, striatum and cerebral cortex of aged mice.. TSG improved the memory and movement functions in aged mice through protecting synapses and inhibiting α-synuclein overexpression and aggregation in multiple brain regions. The results suggest that TSG may be beneficial to the treatment of ageing-related neurodegenerative diseases.

Topics: Aging; alpha-Synuclein; Animals; Avoidance Learning; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cerebral Cortex; Corpus Striatum; Female; Glucosides; Hippocampus; Memory; Memory Disorders; Mice, Inbred C57BL; Motor Activity; Movement Disorders; Neuroprotective Agents; Nootropic Agents; Protein Aggregates; Stilbenes; Synapses; Treatment Outcome

The present study aims to evaluate the effects of pterostilbene on lipopolysaccharide (LPS)-induced learning and memory impairment as well as the possible changes of microglia and neurons. Firstly, learning and memory function was investigated by behavioral tests. Pterostilbene attenuated LPS-induced learning and memory impairment tested by Y-maze and Morris water maze. Secondly, immunohistochemical method was used to study the changes of microglia and neurons. The results showed that pterostilbene produced a significant decrease in the number of Iba-1 and Doublecortin (DCX) positive cells and a significant increase in neuronal nuclear antigen (NeuN)-stained area of neurons in mouse hippocampal compared to the LPS group. Finally, an in vitro study was performed to further confirm the inhibitory effect on microglia activation and protective effect on neurons exerted by pterostilbene. The results demonstrated that pterostilbene significantly inhibited microglia activation, showing the obvious decrease of LPS-induced production of NO, TNF-α and IL-6 in N9 microglial cells. In addition, the viability of SH-SY5Y cells decreased by conditioned media of LPS-activated N9 microglial cells was remarkably recovered by pterostilbene. In summary, the present study demonstrated for the first time that pterostilbene attenuated LPS-induced learning and memory impairment, which may be associated with its inhibitory effect on microglia activation and protective effect on neuronal injury.

Topics: Animals; Cell Line; Cell Line, Tumor; Cell Survival; Disease Models, Animal; Dose-Response Relationship, Drug; Doublecortin Protein; Hippocampus; Humans; Learning Disabilities; Lipopolysaccharides; Maze Learning; Memory Disorders; Microglia; Neurons; Neuroprotective Agents; Nootropic Agents; Random Allocation; Stilbenes

The amyloid-β protein precursor/presenilin 1 (AβPP/PS1) mouse model of Alzheimer's disease (AD) has provided robust neuropathological hallmarks of familial AD-like pattern. AD is a neurodegenerative process that causes severe cognitive impairment; it is characterized by the accumulation of amyloid-β (Aβ) and hyperphosphorylated tau forms and by oxidative and inflammatory processes in brain. Currently, efforts are made to understand biochemical pathways because there is no effective therapy for AD. Resveratrol is a polyphenol that induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of oral resveratrol administration on AβPP/PS1 mice. Long-term resveratrol treatment significantly prevented memory loss as measured by the object recognition test. Moreover, resveratrol reduced the amyloid burden and increased mitochondrial complex IV protein levels in mouse brain. These protective effects of resveratrol were mainly mediated by increased activation of Sirtuin 1 and AMPK pathways in mice. However, an increase has been observed in IL1β and TNF gene expression, indicating that resveratrol promoted changes in inflammatory processes, although no changes were detected in other key actors of the oxidative stress pathway. Taken together, our findings suggest that resveratrol is able to reduce the harmful process that occurs in AβPP/PS1 mouse hippocampus, preventing memory loss.

Topics: Administration, Oral; Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Brain; Disease Models, Animal; Male; Memory Disorders; Memory, Short-Term; Mice, Transgenic; Neuroprotective Agents; Plaque, Amyloid; Presenilin-1; Recognition, Psychology; Resveratrol; Stilbenes

Polydatin is a key component of Polygonum cuspidatum, a herb with medical and nutritional value. The present study investigated the protective effect of polydatin against learning and memory impairment in neonatal rats with hypoxic‑ischemic brain injury (HIBI). The unilateral common carotid artery ligation method was used to generate neonatal HIBI rats. Y‑maze testing revealed that rats with HIBI exhibited memory impairment, while rats with HIBI treated with polydatin displayed enhanced long‑term learning and memory. Of note, polydatin was found to upregulate the expression of hippocampal brain‑derived neurotrophic factor (BDNF) in rats with HIBI. BDNF has a role in protecting HIBI‑induced brain tissue injury and alleviating memory impairment. These findings showed that polydatin had a protective effect against learning and memory impairment in neonatal rats with HIBI and that the protective effect may be mediated through the upregulation of BDNF.

Topics: Animals; Animals, Newborn; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Glucosides; Hippocampus; Hypoxia-Ischemia, Brain; Learning; Memory; Memory Disorders; Protective Agents; Rats; Rats, Sprague-Dawley; Stilbenes; Up-Regulation

Alzheimer's disease (AD), a neurodegenerative disorder exhibiting a gradual decline in cognitive function, is characterized by the presence of neuritic plaques composed of neurofibrillary tangles and amyloid-β (Aβ) peptide. Available drugs for AD therapy have small effect sizes and do not alter disease progression. Several studies have been shown that resveratrol is associated with anti-amyloidogenic properties, but therapeutic application of its beneficial effects is limited. Here we compared the neuroprotective effects of free resveratrol treatment with those of resveratrol-loaded lipid-core nanocapsule treatment against intracerebroventricular injection of Aβ1-42 in rats. Animals received a single intracerebroventricular injection of Aβ1-42 (2 nmol), and 1 day after Aβ infusion, they were administered either free resveratrol (RSV) or resveratrol-loaded lipid-core nanocapsules (5 mg/kg, each 12 h, intraperitoneally), for 14 days. Aβ1-42-infused animals showed a significant impairment on learning memory ability, which was paralleled by a significant decrease in hippocampal synaptophysin levels. Furthermore, animals exhibited activated astrocytes and microglial cells, as well as disturbance in c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-3β (GSK-3β) activation, beyond destabilization of β-catenin levels. Our results clearly show that by using lipid-core nanocapsules, resveratrol was able to rescue the deleterious effects of Aβ1-42 while treatment with RSV presented only partial beneficial effects. These findings might be explained by the robust increase of resveratrol concentration in the brain tissue achieved by lipid-core nanocapsules. Our data not only confirm the potential of resveratrol in treating AD but also offer an effective way to improve the efficiency of resveratrol through the use of nanodrug delivery systems.

Topics: Amyloid beta-Peptides; Animals; Astrocytes; beta Catenin; Cytoprotection; Enzyme Activation; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hippocampus; Injections, Intraventricular; JNK Mitogen-Activated Protein Kinases; Lipids; Male; Memory Disorders; Microglia; Nanocapsules; Neuroprotective Agents; Protein Stability; Rats; Rats, Wistar; Resveratrol; Signal Transduction; Stilbenes; Synapses; Tissue Distribution

Obesity-induced diabetes is associated with chronic inflammation and is considered a risk factor for neurodegeneration. We tested the hypothesis that an AMP-activated protein kinase activator, resveratrol (RES), which is known to exert potent anti-inflammatory effects, would attenuate peripheral and central inflammation and improve memory deficit in mice fed a high-fat diet (HFD). C57BL/6J mice were fed an HFD or an HFD supplemented with RES for 20 weeks. Metabolic parameters in serum were evaluated, and Western blot analysis and immunohistochemistry in peripheral organs and brain were completed. We used the Morris water maze test to study the role of RES on memory function in HFD-treated mice. RES treatment reduced hepatic steatosis, macrophage infiltration, and insulin resistance in HFD-fed mice. In the hippocampus of HFD-fed mice, the protein levels of tumor necrosis factor-α and Iba-1 expression were reduced by RES treatment. Choline acetyltransferase was increased, and the phosphorylation of tau was decreased in the hippocampus of HFD-fed mice upon RES treatment. In particular, we found that RES significantly improved memory deficit in HFD-fed mice. These findings indicate that RES reverses obesity-related peripheral and central inflammation and metabolic derangements and improves memory deficit in HFD-fed diabetic mice.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents, Non-Steroidal; Diet, High-Fat; Fatty Liver; Glucose Tolerance Test; Inflammation; Insulin Resistance; Male; Maze Learning; Memory Disorders; Mice; Obesity; Resveratrol; Stilbenes

Polydatin is one of the most common encountered stilbenes of nature and a key component of the Chinese herb Polygonum cuspidatum. This study is to investigate the effects of polydatin on learning and memory impairments induced by chronic cerebral hypoperfusion in rats, as well as the potential mechanism. Both common carotid arteries and both vertebral arteries occlusion (four-vessel occlusion, 4-VO) induced severe cognitive deficits tested by water maze task, along with oxidative stress in hippocampus. Oral administration of polydatin for 30 days markedly attenuated cognitive deficits compared with the control (p < 0.05). Biochemical determination revealed that polydatin decreased the production of malondialdehyde (MDA) and significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, polydatin effectively alleviated the injuries of cultured neurons induced by oxygen-glucose deprivation (OGD). These results suggest that polydatin exhibit therapeutic potential for vascular dementia, which is most likely related, at least in part, to its anti-oxidant activity and the direct protection of neurons.

Topics: Animals; Catalase; Cells, Cultured; Dementia, Vascular; Disease Models, Animal; Drugs, Chinese Herbal; Fallopia japonica; Glucosides; Hippocampus; Learning; Male; Malondialdehyde; Maze Learning; Memory Disorders; Neurons; Neuroprotective Agents; Protective Agents; Rats; Rats, Sprague-Dawley; Stilbenes; Superoxide Dismutase

Resveratrol (Res) displays potent anti-oxidant activity and is a selective estrogen receptor modulator. The aim of the present study is to investigate whether Res consumption protects ovariectomized (OVX) rats chronically treated with D-galactose (D-gal) from developing memory decline and whether Res administration decreases pathological changes in the endometrium and lumen of the uterus compared with estradiol replacement therapy. Rats were divided into 6 groups: 1) Sham control group; 2) OVX+D-gal 100mg/kg group (OVX+D-gal); 3-5) OVX, D-gal and Res 20, 40, 80 mg/kg treated groups; and 6) OVX, D-gal and estradiol valerate 0.8 mg/kg treated group (ET). Twelve weeks later, in a Morris water maze test, the OVX+D-gal rats exhibited a significant memory impairment compared with the Sham control rats, which was accompanied by decreased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities and an increased thiobarbituric acid reactive substances (TBARS) level in the serum. In addition, the TBARS and protein carbonylation levels increased in the hippocampus. The beneficial roles of the 40 and 80 mg/kg Res treatments were manifested in the prevention of memory decline and markedly decreased oxidant stress indices. The disruption of the cristae in the mitochondria and the irregular nuclei and condensed chromatin in the pyramidal cells of the hippocampal CA1 region were also reduced after Res treatment. Furthermore, edema in the endometrium and lymphocyte infiltration was avoided in all three of the Res-treated groups compared with the ET group. These results suggest that Res is useful not only in protecting OVX+D-gal rats from developing memory decline by increasing the anti-oxidation but also in avoiding the effects on the uterus.

Topics: Animals; Antioxidants; Body Weight; Eating; Emotions; Estradiol; Female; Galactose; Glutathione Peroxidase; Hippocampus; Maze Learning; Memory; Memory Disorders; Motor Activity; Neurons; Ovariectomy; Oxidation-Reduction; Protein Carbonylation; Rats; Rats, Wistar; Resveratrol; Stilbenes; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Uterus

Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring compound found in grapes, wine, peanuts and cranberries. Recently, in vitro and cell culture studies have reported beneficial effects of resveratrol in the neurodegenerative process in Alzheimer's disease (AD). However, in vivo effect of resveratrol in models of learning and memory is not yet evaluated. The present study was performed to examine the effect of resveratrol on cognitive impairment induced by scopolamine, a muscarinic antagonist, in mice.. Scopolamine was administered in a dose of 1 mg/kg intraperitoneally (ip). Cognitive functions were assessed using transfer latency (TL) on elevated plus maze, step-down latency (SDL) on a passive avoidance apparatus and escape latency (EL) in Morris water maze test.. Scopolamine produced significant prolongation of TL, reduction in SDL as well as EL showing cognitive impairment in mice. Pre-treatment with resveratrol (10 mg/kg and 20 mg/kg, ip) for 21 days showed no difference in TL, SDL and EL.. Resveratrol treatment does not reverse scopolamine-induced deficit in cognitive functions in mice.

Topics: Animals; Avoidance Learning; Behavior, Animal; Cognition Disorders; Injections, Intraperitoneal; Maze Learning; Memory Disorders; Mice; Motor Activity; Muscarinic Antagonists; Neuroprotective Agents; Reaction Time; Resveratrol; Scopolamine; Stilbenes; Treatment Outcome

The aim of this study was to evaluate the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from Polygonum multiflorum, on learning/memory deficits in Alzheimer's disease (AD). We randomly divided 24 male Sprague-Dawley rats among 4 groups: (i) the sham-operated group (control); (ii) sham-operated group also treated with TSG (sham+TSG); (iii) beta amyloid treated group (Aβ); and (iv) Aβ treatment group also treated with TSG (Aβ+TSG). Rats in the Aβ and Aβ+TSG groups were treated with Aβ₁₋₄₂ intracerebroventricularly, whereas the control and sham+TSG groups were given phosphate-buffered saline. Rats in the sham+TSG and Aβ+TSG groups were then treated intragastrically with TSG (50 mg·(kg body mass)⁻¹·day⁻¹) for 4 weeks, and rats in the Aβ and control groups were treated with saline. The results from Morris water maze tests, electron microscopy, real-time polymerase chain reaction, and Western blotting demonstrated that Aβ₁₋₄₂ induced impairment in learning and memory, degeneration in synaptic structures, and downregulation of Src and NR2B at the gene and protein level, respectively. These alterations were reversed by the administration of TSG, suggesting that TSG exerts anti-AD properties by protecting synaptic structure and function. TSG-induced upregulation of Src and NR2B may be responsible for this process.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Disease Models, Animal; Glucosides; Hippocampus; Learning Disabilities; Male; Memory Disorders; Nerve Tissue Proteins; Neurons; Neuroprotective Agents; Nootropic Agents; Peptide Fragments; Proto-Oncogene Proteins pp60(c-src); Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Stilbenes; Synaptic Membranes; Up-Regulation

Resveratrol (3,5,4-trihydroxy-trans-stilbene), which is found in grapes and red wine has been shown to protect neuronal cells with its antioxidant activity, improve memory function in dementia and reverse acetylcholine esterase (AChE) activity. The aim of this study was to investigate the effect of resveratrol on emotional and spatial memory in naive rats, as well as on scopolamine- and mecamylamine-induced memory impairment in the passive avoidance and Morris water maze (MWM) tests. Resveratrol (12.5, 25 and 50 mg/kg), scopolamine (0.6 mg/kg) and mecamylamine (10mg/kg) were administered to male Wistar rats. In the passive avoidance test, there was no significant difference in the first day latency between all groups, whereas scopolamine and mecamylamine significantly shortened the second day latency compared to the control group. Resveratrol reversed the effect of scopolamine at all doses used, but it had no effect on mecamylamine-induced memory impairment in the passive avoidance test. Both scopolamine and mecamylamine significantly decreased the time spent in the escape platform quadrant during the probe trial of the MWM test compared to the control group. Resveratrol reversed the effect of scopolamine at all doses, but did not change the effect of mecamylamine in the MWM test. There were no significant differences in the locomotor activities of any of the groups. In conclusion, we suggested that resveratrol had improving effects on learning and memory by acting on muscarinic cholinergic receptors and at least in part, may reverse AChE activity.

Topics: Animals; Avoidance Learning; Male; Maze Learning; Mecamylamine; Memory Disorders; Rats; Rats, Wistar; Reaction Time; Resveratrol; Scopolamine; Stilbenes

Topics: Alcoholism; Animals; Drugs, Chinese Herbal; Glucosides; Male; Maze Learning; Memory Disorders; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; RNA, Messenger; Stilbenes

This study investigated a methanol extract from the leaf and stem of Vitis amurensis (Vitaceae) for possible neuroprotective effects on neurotoxicity induced by amyloid β protein (Aβ) (25-35) in cultured rat cortical neurons and also for antidementia activity in mice. Exposure of cultured cortical neurons to 10 μM Aβ (25-35) for 36 h induced neuronal apoptotic death. At concentrations of 1-10 μg/mL, V. amurensis inhibited neuronal death, the elevation of intracellular calcium ([Ca(2+)](i)) and the generation of reactive oxygen species (ROS), all of which were induced by Aβ (25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of ICR mice with 16 nmol Aβ (25-35) was inhibited by chronic treatment with V. amurensis extract (50 and 100 mg/kg, p.o. for 7 days), as measured by a passive avoidance test. Amurensin G, r-2-viniferin and trans-ɛ-viniferin isolated from V. amurensis also inhibited neuronal death, the elevation of [Ca(2+)](i) and the generation of ROS induced by Aβ (25-35) in cultured rat cortical neurons. These results suggest that the neuroprotective effect of V. amurensis may be partially attributable to these compounds. These results suggest that the antidementia effect of V. amurensis is due to its neuroprotective effect against Aβ (25-35)-induced neurotoxicity and that the leaf and stem of V. amurensis have possible therapeutic roles for preventing the progression of Alzheimer's disease.

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Apoptosis; Benzofurans; Cells, Cultured; Cerebral Cortex; Dibenzocycloheptenes; Dose-Response Relationship, Drug; Embryo, Mammalian; GPI-Linked Proteins; Male; Memory Disorders; Mice; Mice, Inbred ICR; Neurons; Neuroprotective Agents; Peptide Fragments; Phytotherapy; Plant Extracts; Plant Leaves; Plant Stems; Rats; Rats, Sprague-Dawley; Resorcinols; Stilbenes; Vitis

The objective of the present study was to investigate the effect of the administration of resveratrol (RV) on memory and on acetylcholinesterase (AChE) activity in the cerebral cortex, hippocampus, striatum, hypothalamus, cerebellum and blood in streptozotocin-induced diabetic rats. The animals were divided into six groups (n=6-13): Control/saline; Control/RV 10 mg/kg; Control/RV 20 mg/kg; Diabetic/saline; Diabetic/RV 10 mg/kg; Diabetic/RV 20 mg/kg. One day after 30 days of treatment with resveratrol the animals were submitted to behavioral tests and then submitted to euthanasia and the brain structures and blood were collected. The results showed a decrease in step-down latency in diabetic/saline group. Resveratrol (10 and 20 mg/kg) prevented the impairment of memory induced by diabetes. In the open field test, no significant differences were observed between the groups. In relation to AChE activity, a significant increase in diabetic/saline group (P<0.05) was observed in all brain structures compared to control/saline group. However, AChE activity decreased significantly in control/RV10 and control/RV20 (P<0.05) groups in cerebral cortex, hippocampus and striatum, while no significant differences were observed in diabetic/RV10 and diabetic/RV20 groups in all brain structures compared to control/saline group. Blood AChE activity increased significantly in diabetic/saline group (P<0.05) decreased in control/RV10, control/RV20 and diabetic/RV20 groups (P<0.05) compared to control/saline group. In conclusion, the present findings showed that treatment with resveratrol prevents the increase in AChE activity and consequently memory impairment in diabetic rats, demonstrating that this compound can modulate cholinergic neurotransmission and consequently improve cognition.

Topics: Acetylcholinesterase; Animals; Avoidance Learning; Behavior, Animal; Blood Glucose; Cholinesterase Inhibitors; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Memory; Memory Disorders; Random Allocation; Rats; Resveratrol; Stilbenes; Streptozocin

Alzheimer's disease is a complex and multifactorial neurodegenerative disease. Central administration of colchicine, a microtubule-disrupting agent, causes loss of cholinergic neurons and cognitive dysfunction that is associated with excessive free radical generation. The present study was aimed at evaluating the effects of trans-resveratrol in the prevention of colchicine-induced cognitive impairment and oxidative stress in rats. Intracerebroventricular administration of colchicine (15 microg/5 microl) induced impaired cognitive functions in both the Morris water maze task and the elevated plus-maze task. Chronic treatment with resveratrol (10 and 20 mg/kg, p.o.) for a period of 25 days, beginning 4 days prior to colchicine injection, significantly improved the colchicine-induced cognitive impairment. Intracerebroventricular colchicine injection resulted in free radical generation characterized by alterations in oxidative stress markers with a significant increase in malondialdehyde (MDA) and nitrite levels and depletion of reduced glutathione (GSH) activity in the rat brains. It also showed a significant decrease in acetylcholinesterase activity. Besides improving cognitive dysfunction, chronic administration of resveratrol significantly reduced the elevated MDA and nitrite levels and restored the depleted GSH and acetylcholinesterase activity. Results of the present study indicated that trans-resveratrol has a neuroprotective role against colchicine-induced cognitive impairment and associated oxidative stress.

Topics: Acetylcholinesterase; Administration, Oral; Animals; Antioxidants; Behavior, Animal; Brain; Cognition Disorders; Colchicine; Glutathione; Injections, Intraventricular; Lipid Peroxidation; Male; Malondialdehyde; Maze Learning; Memory Disorders; Neuroprotective Agents; Nitrites; Oxidative Stress; Rats; Rats, Wistar; Resveratrol; Space Perception; Stilbenes; Tubulin Modulators

Childhood trauma resulting in traumatic brain injury (TBI) due to accidents and abuse is the major cause of death and dysfunction in the young. Since there are no approved specific pharmacological agents that block the progression of the secondary injury, the current management of TBI is mainly supportive. We aimed to determine the effect of resveratrol on hippocampal damage and behavioral deficits in 7-day-old rat pups subjected to contusion injury. Resveratrol was injected intraperitoneally at the doses of 100 mg/kg of body weight immediately after induction of traumatic injury. Hippocampal damage was examined by cresyl violet staining and behavioral alterations were evaluated using open field and novel object recognition tests 2 weeks after trauma. Histopathological evaluation showed that treatment with a single dose of 100 mg/kg resveratrol (i.p.) after the trauma significantly ameliorated the trauma induced hippocampal neuron loss at ipsilateral and contralateral hippocampal brain regions of rats. Additionally, treatment with resveratrol decreased anxiety and increased cortex/hippocampus dependent memory of animals subjected to blunt head trauma. These results show that acute treatment of resveratrol has a neuroprotective role against trauma induced hippocampal neuron loss and associated cognitive impairment in rats.

Topics: Animals; Animals, Newborn; Antioxidants; Anxiety; Brain Injuries; Cell Death; Cognition Disorders; Hippocampus; Injections, Intraperitoneal; Memory; Memory Disorders; Nerve Degeneration; Neuroprotective Agents; Rats; Rats, Wistar; Resveratrol; Stilbenes; Treatment Outcome