stilbenes and Learning-Disabilities

This paper reviews the brain protective effect and mechanism of Polygonum multiflorum (PM), its extracts and active component, tetrahydroxystilbene-glucoside (2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside) published in recent decade. They have major effects as calcium channel antagonists, antioxidant, cholinomimetic drugs and cholinesterase inhibitors, as well as actions in regulating cell apoptosis and prolonging the ageing. The brain protective mechanism of PM is multi-target, multi-link and multi-way. Therefore, PM has great applicative value in prevention and treatment of senile neuropathies, such as Alzheimer's disease, Parkinson's disease and vascular dementia, etc.

Topics: Animals; Antioxidants; Calcium Channel Blockers; Drugs, Chinese Herbal; Glucosides; Humans; Learning Disabilities; Neuroprotective Agents; Plant Extracts; Polygonum; Stilbenes

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

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

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

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 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

To investigate learning-memory deficit in different ages of AD-like APP transgenic mice and to observe the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), which is the main component of Polygonum multiflorum, on learning-memory abilities.. PDAPPV717I transgenic (Tg) mice were randomly divided into 3 model groups (4, 10 and 16 months old mice) and TSG treated (at doses 120 and 240 micromol/kg/d) groups. TSG was administered to some Tg mice with an age range 4-10 months. In untreated 10 months old Tg mice, the TSG was administrated to those falling in the age range 10-16 months. For the control group we adopted the same age and background C57BL/6J mice. The learning-memory ability was measured by applying Morris water maze (MWM) and object recognition test (ORT).. In the 4 months old PDAPPV717I Tg mice, the learning-memory deficit was detected. The escape latency in MWM was prolonged, and the discrimination index decreased in ORT. In the 10 months old Tg mice, the learning-memory deficit was aggravated. TSG improved all spatial learning-memory impairment in MWM as well as the object recognition impairment in ORT. In the 16 months old Tg mice, the learning-memory deficit remained to exist but abated a lot. TSG showed significant improvement in learning-memory ability in both MWM and ORT.. PDAPPV717I transgenic mice with an age range 4-16 months revealed the existence of learning-memory deficit compared with the control group. Tetrahydroxystilbene glucoside not only prevents, i.e. at an early stage, the learning-memory deficit in AD-like model, but also can reverse the learning-memory deficit in the late stage of AD-like model. Thus, TSG could be considered among the future therapeutic drugs indicated for the treatment of AD.

Topics: Age Factors; Aging; Alzheimer Disease; Amyloid beta-Protein Precursor; Analysis of Variance; Animals; Disease Models, Animal; Glucosides; Learning Disabilities; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pattern Recognition, Visual; Stilbenes

Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Dyskinesia, Drug-Induced; Failure to Thrive; Female; Fetal Alcohol Spectrum Disorders; Humans; Intellectual Disability; Learning Disabilities; Maternal-Fetal Exchange; Neuroblastoma; Phenytoin; Pregnancy; Prenatal Exposure Delayed Effects; Stilbenes; Vaginal Neoplasms