The effects of physical exercise therapy on weight control: its regulation of adipocyte physiology and metabolic capacity.

Factors associated with increased body mass, including dyslipidemia, hypertension, insulin resistance, vascular endothelial dysfunction and sleep disorders, may contribute to the exacerbation of cardiovascular disease. These health problems associated with obesity are caused by accumulated metabolism and physical and emotional stress. Lifestyle, especially exercise, is a major therapeutic strategy for the treatment and management of obesity-induced metabolic problems. Metabolic disease often co-occurs with abdominal obesity. Exercise is necessary for the treatment of obesity, diabetes and cardiovascular disease. A potential benefit of exercise is to promote fat burning and energy use increases both during exercise itself and in the post-exercise period. Exercise suppresses basal metabolic rate and also has many health benefits. Why should we exercise to lose weight? Does physical activity help lower blood pressure, blood cholesterol, and blood sugar? In this article, we review the positive effects of physical exercise on weight maintenance and weight loss, and the effectiveness of physical exercise on the treatment and prevention of metabolic syndrome.

Sedative-Hypnotic Effects of Glycine max Merr. Extract and Its Active Ingredient Genistein on Electric-Shock-Induced Sleep Disturbances in Rats.

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active compound, genistein (GE), using electroencephalography (EEG) analysis in an electric foot shock (EFS)-stressed rat. The underlying neural mechanisms of their beneficial effects were determined by assessing corticotropin-releasing factor (CRF), serotonin (5-HT), and c-Fos immunoreactivity in the brain using immunohistochemical methods. In addition, the 5-HT2C receptor binding assay was performed because it is considered a major target of antidepressants and sleep aids. In the binding assay, GM displayed binding affinity to the 5-HT2C receptor (IC50 value of 14.25 ± 11.02 µg/mL). GE exhibited concentration-dependent binding affinity, resulting in the binding of GE to the 5-HT2C receptor (IC50, 77.28 ± 26.57 mg/mL). Administration of GM (400 mg/kg) increased non-rapid eye movement (NREM) sleep time. Administration of GE (30 mg/kg) decreased wake time and increased rapid eye movement (REM) and NREM sleep in EPS-stressed rats. In addition, treatment with GM and GE significantly decreased c-Fos and CRF expression in the paraventricular nucleus (PVN) and increased 5-HT levels in the dorsal raphe in the brain. Overall, these results suggest that GM and GE have antidepressant-like effects and are effective in sleep maintenance. These results will benefit researchers in developing alternatives to decrease depression and prevent sleep disorders.

A Randomized Double-Blind, Placebo-Controlled Study on Anti-Stress Effects of Nelumbinis Semen.

Introduction: Depression is a serious and common mental disease that causes low mood and loss of interest in activities. Nelumbinis semen (NS) has been widely used as a treatment for depression for hundreds of years in many Asian countries. Water extract of nelumbinis semen (WNS) is a standardized herbal medicine made from NS. Methods: The objective of the present research was to perform a randomized, double-blind, placebo-controlled trial to estimate the efficacy of WNS for improving depressive and stress symptoms using Beck depression inventory (BDI) and the stress response inventory (SRI) in 45 adults diagnosed with major depression or other forms of depressive disorders. They were randomized to either a placebo-treated group, a 2.4 g per day WNS-treated group, or a 4.8 g per day WNS-treated group. BDI and SRI were determined in order to evaluate changes in depression before and after two weeks of WNS treatment. Results: The average BDI and SRI of the 2.4 g WNS-treated group were significantly (p < 0.05) improved compared to those of the placebo-treated group. Their BDI subscale A (negative attitudes towards self) and subscale C (somatic disturbances), SRI E, and depression subscale of SRI were substantially shorter (p < 0.05). In addition, an analysis of collected EEG data of participants showed a significant increase in alpha/beta activity in the 4.8 g WNS-treated group, which might be explained as an advancement of their depression symptoms (p < 0.05). Conclusions: These results suggest that WNS treatment can decrease depression. Our study provides preliminary evidence for the safety of WNS and its potential to decrease depression.

Effect of Modified Yukmijihwang-Tang on Sleep Quality in the Rat.

Many plants have been used in Korean medicine for treating insomnia. However, scientific evidence for their sedative activity has not been fully investigated. Thus, this study was carried out to investigate the sedative effects of the extracts of medicinal plants, including Yukmijihwang-tang and its various modified forms through the 5-HT2c receptor binding assay, and to further confirm its sleep-promoting effects and the underlying neural mechanism in rats utilizing electroencephalography (EEG) analysis. Enzyme-linked immunosorbent assay (ELISA) was used to measure serotonin (5-HT) in the brain. The water extracts of modified Yukmijihwang-tang (YmP) displayed binding affinity to the 5-HT2C receptor (IC50 value of 199.9 µg/mL). YmP (50 mg/kg) administration decreased wake time and increased REM and NREM sleep based on EEG data in rats. Additionally, treatment with YmP significantly increased the 5-HT level in the hypothalamus. In conclusion, the sedative effect of YmP can be attributed to the activation of the central serotonergic systems, as evidenced by the high affinity of binding of the 5-HT2C receptor and increased 5-HT levels in the brain of the rat. This study suggests that YmP can be a new material as a sleep inducer in natural products.

Anti-Inflammatory Effect of Three Isolated Compounds of Physalis alkekengi var. franchetii (PAF) in Lipopolysaccharide-Activated RAW 264.7 Cells.

(1) Background: Three isolated compounds from Physalis alkekengi var. franchetii (PAF) have been investigated to possess a variety of biological activities. Their structures were elucidated by spectroscopic analysis (Ultraviolet (UV), High-resolution electrospray mass spectrometry (HR-ESI-Ms), and their anti-inflammatory effects were evaluated in vitro; (2) Methods: To investigate the mechanisms of action of PAF extracts and their isolated compounds, their anti-inflammatory effects were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). RAW 264.7 cells were treated with different concentrations of Physalis alkekengi var. franchetii three isolated compounds of PAF for 30 min prior to stimulation with or without LPS for the indicated times. The inflammatory cytokines, interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were determined using reverse transcription-polymerase chain (RT-PCR); (3) Results Treatment of RAW 264.7 cells with LPS alone resulted in significant increases in inflammatory cytokine production as compared to the control group (p < 0.001). However, with the treatment of isophysalin B 100 µg/mL, there was a significant decrease in the mRNA expression levels of TNF-α in LPS-stimulated raw 264.7 cells (p < 0.001). With treatment of physalin 1−100 µg/mL, there was a markedly decrease in the mRNA expression levels of TNF-α in LPS stimulated raw 264.7 (p < 0.05). Moreover, TNF-α mRNA (p < 0.05) and IL-1ß mRNA (p < 0.001) mRNA levels were significantly suppressed after treatment with 3',7-dimethylquercetin in LPS stimulated Raw 264.7 cells; (4) Conclusions: These findings suggest that three isolated compounds from can suppress inflammatory responses in LPS stimulated macrophage.

Neuroprotective effects of ex vivo-expanded regulatory T cells on trimethyltin-induced neurodegeneration in mice.

BACKGROUND: Trimethyltin (TMT) is a potent neurotoxicant that leads to hippocampal neurodegeneration. Regulatory T cells (Tregs) play an important role in maintaining the immune balance in the central nervous system (CNS), but their activities are impaired in neurodegenerative diseases. In this study, we aimed to determine whether adoptive transfer of Tregs, as a living drug, ameliorates hippocampal neurodegeneration in TMT-intoxicated mice. METHODS: CD4+CD25+ Tregs were expanded in vitro and adoptively transferred to TMT-treated mice. First, we explored the effects of Tregs on behavioral deficits using the Morris water maze and elevated plus maze tests. Biomarkers related to memory formation, such as cAMP response element-binding protein (CREB), protein kinase C (PKC), neuronal nuclear protein (NeuN), nerve growth factor (NGF), and ionized calcium binding adaptor molecule 1 (Iba1) in the hippocampus were examined by immunohistochemistry after killing the mouse. To investigate the neuroinflammatory responses, the polarization status of microglia was examined in vivo and in vitro using real-time reverse transcription polymerase chain reaction (rtPCR) and Enzyme-linked immunosorbent assay (ELISA). Additionally, the inhibitory effects of Tregs on TMT-induced microglial activation were examined using time-lapse live imaging in vitro with an activation-specific fluorescence probe, CDr20. RESULTS: Adoptive transfer of Tregs improved spatial learning and memory functions and reduced anxiety in TMT-intoxicated mice. Additionally, adoptive transfer of Tregs reduced neuronal loss and recovered the expression of neurogenesis enhancing molecules in the hippocampi of TMT-intoxicated mice. In particular, Tregs inhibited microglial activation and pro-inflammatory cytokine release in the hippocampi of TMT-intoxicated mice. The inhibitory effects of TMT were also confirmed via in vitro live time-lapse imaging in a Treg/microglia co-culture system. CONCLUSIONS: These data suggest that adoptive transfer of Tregs ameliorates disease progression in TMT-induced neurodegeneration by promoting neurogenesis and modulating microglial activation and polarization.

Sedative-Hypnotic Activity of the Water Extracts of Coptidis Rhizoma in Rodents.

Many medicinal plants have been used in Asia for treating a variety of mental diseases, including insomnia and depression. However, their sedative-hypnotic effects and mechanisms have not been clarified yet. Accordingly, the objective of this study was to investigate the sedative-hypnotic effects of water extracts of five medicinal plants: Coptidis Rhizoma, Lycii Fructus, Angelicae sinensis Radix, Bupleuri Radix, and Polygonum multiflorum Thunberg. The binding abilities of five medicinal plant extracts to the GABAA-BZD and 5-HT2C receptors were compared. Their abilities to activate arylalkylamine N-acetyltransferase (AANAT), a melatonin synthesis enzyme, in pineal cells were also determined. Following in vitro tests, the sedative and hypnotic activities of extracts with the highest activities were determined in an animal sleep model. In the binding assay, the water extracts of Coptidis Rhizoma (WCR) showed high binding affinity to the GABAA-BZD and 5-HT2C receptors in a dose-dependent manner. Additionally, WCR increased the AANAT activity up to five times compared with the baseline level. Further animal sleep model experiments showed that WCR potentiated pentobarbital-induced sleep by prolonging the sleep time. It also decreased the sleep onset time in mice. In addition, WCR reduced wake time and increased non-rapid eye movement (NREM) sleep without EEG power density (percentages of δ, θ, and α waves) during NREM sleep in rats. WCR could effectively induce NREM sleep without altering the architectural physiologic profile of sleep. This is the first report of the sedative-hypnotic effect of Coptidis Rhizoma possibly by regulating GABAA and 5-HT2C receptors and by activating AANAT activity.

Pre/post-natal exposure to microplastic as a potential risk factor for autism spectrum disorder.

In common with the increase in environmental pollution in the past 10 years, there has also been a recent increase in the prevalence of autism spectrum disorder (ASD). In this regard, we hypothesized that exposure to microplastics is a potential risk factor for ASD. To evaluate the validity of this hypothesis, we initially examined the accumulation of polyethylene (PE) in the brains of mice and then assessed the behavioral effects using mouse models at different life stages, namely, prenatal, post-weaning, puberty, and adult models. Based on typical behavioral assessments of autistic traits in the model mice, we established that ASD-like traits were induced in mice after PE feeding. In addition, we examined the induction of ASD-like traits in response to microplastic exposure using positron emission tomography, magnetic resonance spectroscopy, quantitative real-time polymerase chain reaction, microarray, and microbiome analysis. We believe these findings provide evidence in microplastics as a potential risk factor for ASD.

Anti-Obesity Effect of Chitoglucan in High-Fat-Induced Obesity Mice.

BACKGROUND: Chitoglucan (CG) is a bioactive component obtained from Flammulina velutipes Sing, an edible mushroom, which is known to have an anti-obesity effect. However, its biological and hormonal activities in alleviating obesity through regulation of adipocyte-derived proteins have not been examined yet. PURPOSE: The present study aimed to investigate the anti-obesity effects of chitoglucan and its hormonal mechanisms in high-fat diet (HFD)-induced mice. METHODS: The mice were fed either a normal diet (Normal group) or a high fat diet (HFD group) over 6 weeks. The HFD fed mice were administered with saline (HFD group), adipex (HFD + adipex group), chitoglucan 50, 150, or 300 mg/kg/day for 3 weeks (HFD + CG groups). The food consumption, body weight, fat contents, and the levels of serum leptin and resistin were assessed after treatment of chitoglucan. RESULTS: the HFD produced a marked increase in body and fat weights after 6 weeks of feeding compared with the Normal group. Administration of chitoglucan for 3 weeks tended to reduce body weight and significantly decreased parametrical adipose tissues in HFD groups. The level of serum leptin in the HFD group was markedly higher than that in the Normal group, whereas the level of leptin in the chitoglucan treated groups was significantly decreased in comparison with the HFD group. In addition, the level of serum resistin in high-fat diet group tended to be more increased than Normal group. However, the serum resistin level was significantly reduced in HF diet groups after treatment with chitoglucan (50 mg/kg or 150 mg/kg). CONCLUSION: Collectively, these data suggest that chitoglucan from the Flammulina velutipes may be useful in the treatment of high diet-induced obesity and metabolic syndrome.

Effect of Hibiscus syriacus Linnaeus extract and its active constituent, saponarin, in animal models of stress-induced sleep disturbances and pentobarbital-induced sleep.

Treatment of sleep disorders promotes the long-term use of commercially available sleep inducers that have several adverse effects, including addiction, systemic fatigue, weakness, loss of concentration, headache, and digestive problems. Therefore, we aimed to limit these adverse effects by investigating a natural product, the extract of the Hibiscus syriacus Linnaeus flower (HSF), as an alternative treatment. In the electric footshock model, we measured anxiety and assessed the degree of sleep improvement after administering HSF extract. In the restraint model, we studied the sleep rate using PiezoSleep, a noninvasive assessment system. In the pentobarbital model, we measured sleep improvement and changes in sleep-related factors. Our first model confirmed the desirable effects of HSF extract and its active constituent, saponarin, on anxiolysis and Wake times. HSF extract also increased REM sleep time. Furthermore, HSF extract and saponarin increased the expression of cortical GABAA receptor α1 (GABAAR α1) and c-Fos in the ventrolateral preoptic nucleus (VLPO). In the second model, HSF extract and saponarin restored the sleep rate and the sleep bout duration. In the third model, HSF extract and saponarin increased sleep maintenance time. Moreover, HSF extract and saponarin increased cortical cholecystokinin (CCK) mRNA levels and the expression of VLPO c-Fos. HSF extract also increased GABAAR α1 mRNA level. Our results suggest that HSF extract and saponarin are effective in maintaining sleep and may be used as a novel treatment for sleep disorder. Eventually, we hope to introduce HSF and saponarin as a clinical treatment for sleep disorders in humans.

The Effect of Earthing Mat on Stress-Induced Anxiety-like Behavior and Neuroendocrine Changes in the Rat.

Grounding is a therapeutic technique that involves doing activities that "ground" or electrically reconnect us to the earth. The physiological effects of grounding have been reported from a variety of perspectives such as sleep or pain. However, its anti-stress efficacy is relatively unknown. The present study investigated the stress-related behavioral effects of earthing mat and its neurohormonal mechanisms in the Sprague−Dawley male rat. Rats were randomly divided into four groups: the naïve normal (Normal), the 21 days immobilization stressed (Control), the 21 days stressed + earthing mat for 7 days (A7) or 21 days (A21) group. The depressive-and anxiety like behaviors were measured by forced swimming test (FST), tail suspension test (TST) and elevated plus maze (EPM). Using immunohistochemistry, the expression of corticotrophin-releasing factor (CRF) and c-Fos immunoreactivity were analyzed in the brain. In the EPM, time spent in the open arm of the earthing mat groups was significantly increased compared to the Control group (p < 0.001), even though there were without effects among groups in the FST and TST. The expression of CRF immunoreactive neurons in the earthing mat group was markedly decreased compared to the Control group. Overall, the earthing mat reduced stress-induced behavioral changes and expression of c-Fos and CRF immunoreactivity in the brain. These results suggest that the earthing mat may have the potential to improve stress-related responses via the regulation of the corticotrophinergic system.

Regulatory role of cytokines on etiology of depression in animal models: their biological mechanisms and clinical implication with physical exercise.

It has been known that chronic psychological or physical stress elicits depressive behaviors (learned helplessness, anhedonia, anxiety, etc.) and also activates to release proinflammatory cytokines in the brain. Especially, postmenopausal women under stress condition exacerbates neuroimmune systems and mood disorder. Repeated restraint stress in the ovariectomized female rats poses an immune challenge which was capable of inducing depressive-like behaviors, promoting exaggerated corticosterone responses and changing the proinflammatory cytokine expression such as interleukin (IL)-1ß in the brain. Also, anti-inflammatory cytokines including IL-4 are known to regulate inflammation caused by immune response or stress challenge. Furthermore, some studies reported that physical activity can reduce stress hormones and improve personal immunity. Physical exercise has been shown to be associated with decreased symptoms of depression and anxiety, and with improved physical health, immunological function, and psychological well-being. This paper aims to discuss an overview of how stress shapes neuroimmune response and diverse roles of cytokines in animals models, acting on depressive-like behavioral changes; some beneficial aspects of exercise on stress-related disorders are addressed.

Neuronal mechanisms of ginseng on antiobesity effects: implication of its synergistic benefits with physical exercise.

Obesity is a chronic disease of increasing prevalence in most countries, which leads to substantial increase in morbidity, and mortality in association with diabetes, hyperlipidaemia, hypertension, and other cardiovascular diseases. Many factors have been attributed to an epidemic of obesity including sedentary lifestyle, high-fat diets (HFD), and consumption of large amount of modern fast foods. Panax ginseng C. A. Meyer (PG) has several pharmacological and physiological effects. In particular, PG and saponin fractions from PG show a variety of efficacies such as antifatigue, hyperlipidemia, hypertension and noninsulin-dependent diabetes mellitus and obesity. We have revealed that ginseng and ginsenosides can decrease food intake energy expenditure by stimulating appetite regulatory hormones and can reduce energy intake. Exercise/ physical activity is well known as modality for treating the disease of overweight and obesity. It is suggested that natural products and their combinations with exercise may produce a synergistic activity that increases their bioavailability and action on multiple molecular targets, offering advantages over chemical treatments. This review is aimed at evaluating the antiobesity efficacy of ginseng and ginsenosides and delineating the mechanisms by which they function. Finally, we review information regarding interactions between ginseng and physical exercise in protecting against weight gain and obesity.

Regulation of habenular G-protein gamma 8 on learning and memory via modulation of the central acetylcholine system.

Guanine nucleotide binding protein (G protein) gamma 8 (Gng8) is a subunit of G proteins and expressed in the medial habenula (MHb) and interpeduncular nucleus (IPN). Recent studies have demonstrated that Gng8 is involved in brain development; however, the roles of Gng8 on cognitive function have not yet been addressed. In the present study, we investigated the expression of Gng8 in the brain and found that Gng8 was predominantly expressed in the MHb-IPN circuit of the mouse brain. We generated Gng8 knockout (KO) mice by CRISPR/Cas9 system in order to assess the role of Gng8 on cognitive function. Gng8 KO mice exhibited deficiency in learning and memory in passive avoidance and Morris water maze tests. In addition, Gng8 KO mice significantly reduced long-term potentiation (LTP) in the hippocampus compared to that of wild-type (WT) mice. Furthermore, we observed that levels of acetylcholine (ACh) and choline acetyltransferase (ChAT) in the MHb and IPN of Gng8 KO mice were significantly decreased, compared to WT mice. The administration of nAChR α4ß2 agonist A85380 rescued memory impairment in the Gng8 KO mice, suggesting that Gng8 regulates cognitive function via modulation of cholinergic activity. Taken together, Gng8 is a potential therapeutic target for memory-related diseases and/or neurodevelopmental diseases.

The Differential Role of Cytokines on Stress Responses in a Menopause Rat Model.

Menopause is a risk factor of anxiety and depression. Also, psychoneurological symptoms are shown in almost all women in the perimenopausal period. The present study investigated if repeated stress modulates behavioral changes or the balance of pro- and anti-inflammatory cytokines in ovariectomized (OVX) rats. Albino SD female rats were randomly divided into four groups: the naïve normal group (NOR), a surgically ovariectomized group (OVX), the only stressed group (ST), and the OVX and stressed groups (OVX + ST). We performed a battery of tests such as the forced swimming test (FST), the sucrose intake, and social exploration. In the same animals, corticosterone (CORT) was assessed in the serum, and also, two representative cytokines (IL-1ß and IL-4) were examined in different brain regions after all the behavior sessions for all the experimental groups. The OVX + ST group showed more immobility time in FST than the OVX group or the ST group. Also, the OVX + ST group tended to have a decreased active social exploration and sucrose solution intake compared to the OVX group or ST group. The serum concentration of CORT of the OVX + ST group was higher than the OVX group or ST group and also the level of CORT in OVX + ST was markedly increased compared to the NOR group. In the brain, the number of IL-1ß immunoreactive neurons of the OVX + ST group was increased compared to the NOR group. The OVX + ST group tended to have an increase in IL-1ß-positive neurons compared to the OVX or ST group. However, the number of IL-4 immunoreactive neurons of the OVX + ST group was markedly decreased compared with the NOR group. Also, the IL-4-positive neurons in the OVX + ST group was significantly decreased when compared to the ST group. These results indicate that ovariectomy and stress combine to increase the depressive-like behaviors and neuroinflammatory responses. Together, these data show neuroinflammation as a potential contributor to depressive-like symptoms during menopausal transition.

Antidepressant effect and neural mechanism of Acer tegmentosum in repeated stress-induced ovariectomized female rats.

Acer tegmentosum (ATM) has antioxidant and anti-adipogenic activity. However, few studies have investigated the pharmacological activity or mechanism of ATM as an antidepressant agent. We assessed the antidepressant effect of ATM in modulating menopausal depressive symptoms and its mechanisms in ovariectomized (OVX) and repeatedly stressed (RS) female rats. The female rats were randomly divided into four groups: (1) naïve normal (normal) group, (2) OVX + repeated stress + saline-treated (control) group, (3) OVX + repeated stress + ATM (100 mg•kg-1)-treated (ATM100) group and (4) OVX + repeated stress + ATM (400 mg•kg-1)-treated (ATM400) group. We performed a battery of tests, such as the forced swimming test (FST), the sucrose intake test, and social exploration. After behavior testing, serum corticosterone levels were examined, followed by immunohistochemical determination of c-Fos, tyrosine hydroxylase (TH), and interleukin-1 beta (IL-1ß) expression in the brain. ATM administration was associated with significantly decreased immobility time in the FST. Also, the control group tended to have decreased sucrose intake and social exploration compared with the normal group. However, ATM treatment was associated with markedly increased sucrose intake and active social exploration. In the paraventricular nucleus, c-Fos and IL-1ß expression were significantly decreased in the ATM400 group compared with the control group. Compared with the control group, high-dose ATM administration was also associated with markedly decreased expression of TH-immunoreactive neurons in the locus coeruleus. The study findings demonstrated that ATM treatment effectively decreased behavioral and pathophysiological depression-like responses.

Depression-like behaviors induced by defective PTPRT activity through dysregulated synaptic functions and neurogenesis.

PTPRT has been known to regulate synaptic formation and dendritic arborization of hippocampal neurons. PTPRT-/- null and PTPRT-D401A mutant mice displayed enhanced depression-like behaviors compared with wild-type mice. Transient knockdown of PTPRT in the dentate gyrus enhanced the depression-like behaviors of wild-type mice, whereas rescued expression of PTPRT ameliorated the behaviors of PTPRT-null mice. Chronic stress exposure reduced expression of PTPRT in the hippocampus of mice. In PTPRT-deficient mice the expression of GluR2 (also known as GRIA2) was attenuated as a consequence of dysregulated tyrosine phosphorylation, and the long-term potentiation at perforant-dentate gyrus synapses was augmented. The inhibitory synaptic transmission of the dentate gyrus and hippocampal GABA concentration were reduced in PTPRT-deficient mice. In addition, the hippocampal expression of GABA transporter GAT3 (also known as SLC6A11) was decreased, and its tyrosine phosphorylation was increased in PTPRT-deficient mice. PTPRT-deficient mice displayed reduced numbers and neurite length of newborn granule cells in the dentate gyrus and had attenuated neurogenic ability of embryonic hippocampal neural stem cells. In conclusion, our findings show that the physiological roles of PTPRT in hippocampal neurogenesis, as well as synaptic functions, are involved in the pathogenesis of depressive disorder.

Neuroprotective Effect of Bean Phosphatidylserine on TMT-Induced Memory Deficits in a Rat Model.

BACKGROUND: Trimethyltin (TMT) is a potent neurotoxin affecting various regions of the central nervous system, including the neocortex, the cerebellum, and the hippocampus. Phosphatidylserine (PS) is a membrane phospholipid, which is vital to brain cells. We analyzed the neuroprotective effects of soybean-derived phosphatidylserine (Bean-PS) on cognitive function, changes in the central cholinergic systems, and neural activity in TMT-induced memory deficits in a rat model. METHODS: The rats were randomly divided into an untreated normal group, a TMT group (injected with TMT + vehicle), and a group injected with TMT + Bean-PS. The rats were treated with 10% hexane (TMT group) or TMT + Bean-PS (50 mg·kg-1, oral administration (p.o.)) daily for 21 days, following a single injection of TMT (8.0 mg/kg, intraperitoneally (i.p.)). The cognitive function of Bean-PS was assessed using the Morris water maze (MWM) test and a passive avoidance task (PAT). The expression of acetylcholine transferase (ChAT) and acetylcholinesterase (AchE) in the hippocampus was assessed via immunohistochemistry. A positron emission tomography (PET) scan was used to measure the glucose uptake in the rat brain. RESULTS: Treatment with Bean-PS enhanced memory function in the Morris water maze (MWM) test. Consistent with the behavioral results, treatment with Bean-PS diminished the damage to cholinergic cells in the hippocampus, in contrast to those of the TMT group. The TMT+Bean-PS group showed elevated glucose uptake in the frontal lobe of the rat brain. CONCLUSION: These results demonstrate that Bean-PS protects against TMT-induced learning and memory impairment. As such, Bean-PS represents a potential treatment for neurodegenerative disorders, such as Alzheimer's disease.