Exercise before pregnancy exerts protective effect on prenatal stress-induced impairment of memory, neurogenesis, and mitochondrial function in offspring.

Stress during pregnancy has a negative effect on the fetus. However, maternal exercise has a positive effect on the cognitive function of the fetus and alleviates the negative effects of stress. This study aimed to demonstrate whether exercise before pregnancy has a protective effect on prenatal stress-induced impairment of memory, neurogenesis and mitochondrial function in mice offspring. In this experiment, immunohistochemistry, Western blot, measurement of mitochondria oxygen respiration, and behavior tests were performed. Spatial memory and short-term memory of the offspring from the prenatal stress with exercise were increased compared to the offspring from the prenatal stress. The numbers of doublecortin-positive and 5-bromo-2'-deoxyuridine-positive cells in the hippocampal dentate gyrus of the offspring from the prenatal stress with exercise were higher compared to the offspring from the prenatal stress. The expressions of brain-derived neurotrophic factor, postsynaptic density 95 kDa, and synaptophysin in the hippocampus of the offspring from the prenatal stress with exercise were enhanced compared to the offspring from the prenatal stress. Oxygen consumption of the offspring from the prenatal stress with exercise were higher compared to the offspring from the prenatal stress. Exercise before pregnancy alleviated prenatal stress-induced impairment of memory, neurogenesis, and mitochondrial function. Therefore, exercise before pregnancy may have a protective effect against prenatal stress of the offspring.

Enhancing Post-Surgical Rehabilitation Outcomes in Patients with Chronic Ankle Instability: Impact of Subtalar Joint Axis Balance Exercises Following Arthroscopic Modified Broström Operation.

Background and Objectives: This study aimed to evaluate the effects of subtalar joint axis-based balance exercises on the anterior talofibular ligament (ATFL) thickness, ankle strength, and ankle stability after an arthroscopic modified Broström operation (AMBO) for chronic ankle instability (CAI). Materials and Methods: The study included 47 patients diagnosed with CAI who underwent AMBO and were randomly divided into three groups: control (n = 11), general balance exercise (n = 17), and subtalar joint axis balance exercise (n = 19), regardless of the affected area. Participants in the exercise rehabilitation group performed exercises for 60 min twice a week for six weeks, starting six weeks after AMBO. ATFL thickness, ankle strength, and ankle dynamic stability were measured using musculoskeletal ultrasonography, Biodex, and Y-balance test, respectively, before and after treatment. Results: Compared with the remaining groups, the subtalar joint axis balance exercise group had reduced ATFL thickness (p = 0.000), improved ankle strength for eversion (p = 0.000) and inversion (p = 0.000), and enhanced ankle stability (p = 0.000). Conclusions: The study results suggest that subtalar joint axis-based balance exercises may contribute to the early recovery of the ankle joint after AMBO.

The effects of dietary self-monitoring intervention on anthropometric and metabolic changes via a mobile application or paper-based diary: a randomized trial.

BACKGROUND/OBJECTIVES: Weight loss via a mobile application (App) or a paper-based diary (Paper) may confer favorable metabolic and anthropometric changes. SUBJECTS/METHODS: A randomized parallel trial was conducted among 57 adults whose body mass indices (BMIs) were 25 kg/m2 or greater. Participants randomly assigned to either the App group (n = 30) or the Paper group (n = 27) were advised to record their foods and supplements through App or Paper during the 12-week intervention period. Relative changes of anthropometries and biomarker levels were compared between the 2 intervention groups. Untargeted metabolic profiling was identified to discriminate metabolic profiles. RESULTS: Out of the 57 participants, 54 participants completed the trial. Changes in body weight and BMI were not significantly different between the 2 groups (P = 0.11). However, body fat and low-density lipoprotein (LDL)-cholesterol levels increased in the App group but decreased in the Paper group, and the difference was statistically significant (P = 0.03 for body fat and 0.02 for LDL-cholesterol). In the metabolomics analysis, decreases in methylglyoxal and (S)-malate in pyruvate metabolism and phosphatidylcholine (lecithin) in linoleic acid metabolism from pre- to post-intervention were observed in the Paper group. CONCLUSIONS: In the 12-week randomized parallel trial of weight loss through a App or a Paper, we found no significant difference in change in BMI or weight between the App and Paper groups, but improvement in body fatness and LDL-cholesterol levels only in the Paper group under the circumstances with minimal contact by dietitians or health care providers. Trial Registration: Clinical Research Information Service Identifier: KCT0004226.

Treadmill exercise ameliorates chemotherapy-induced memory impairment through Wnt/ß-catenin signaling pathway.

Doxorubicin (DOX) is a widely used chemotherapy drug for various cancers and it is known to induce cognitive impairment. The aim of this study was to investigate the effect of treadmill exercise on chemotherapy-induced memory impairment. We assessed whether DOX affects inflammation, mitochondrial Ca2+ retention capacity, and Wnt/ß-catenin signaling. Male Sprague-Dawley rats were divided into control group, exercise group, DOX-injection group, and DOX-injection and exercise group. To create a DOX-induced memory impairment model, animals were injected intraperitoneally with DOX (2 mg/kg) dissolved in saline solution once a week for 4 weeks. Treadmill exercise was performed once a day, 5 days a week, for 8 consecutive weeks. Short-term memory was determined using the step-down avoidance test. Western blot was performed for the proinflammatory cytokines, Wnt/ß-catenin signaling, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) in the hippocampus. Mitochondrial Ca2+ retention capacity in the hippocampus was also measured. DOX-injection rats showed deterioration of short-term memory along with decreased expression of BDNF and TrkB in the hippocampus. Levels of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, were increased in the DOX-injection rats. Wnt/ß-catenin signaling was activated and mitochondrial Ca2+ retention capacity was decreased in the DOX-injection rats. However, treadmill exercise alleviated short-term memory impairment, decreased proinflammatory cytokines, increased BDNF and TrkB expression, and enhanced mitochondrial Ca2+ retention capacity. Treadmill exercise restorated Wnt/ß-catenin signaling pathway. This study demonstrated that treadmill exercise can be used for patients undergoing chemotherapy with DOX.

Effects of exercise and microbiota transplant on the memory of obesity-induced mice.

This study attempted to investigate the association between changes in the intestinal environment and the brain using a model that received aerobic exercise and microbiome transplantation. All mice were fed a diet containing 60% fat. For the obesity with nonexercise microbiome transplantation group, feces from donors that did not undergo exercise were administered. For the obesity with exercise microbiome trans-plantation group, feces from donors who underwent exercise were administered. Treadmill exercise started 16 weeks after the intake of the high fat feeding and continued for 24 weeks. The short-term memory and spatial learning memory were determined by step-down avoidance test and Morris water maze task, immunohistochemistry for glial fibrillary acidic protein, western blot analysis for brain-derived neurotrophic factor and tropomyosin receptor kinase B were performed in the hippocampus. Exercise was the most effective way to reduce obesity, improve memory function, suppress inflammation, and increase brain-derived neurotrophic factor expression. Intestinal microbiota transplantation was the second most effective after exercise. However, there was no significant difference in the fecal microbiota transplant group according to whether or not exercise was performed.

The effects of exercise and diet on mental status, insulin signaling pathway, and microbiome in obese mice.

The aim of this study was to investigate the effects of exercise and diet on mental status, insulin signaling pathway, serotonin synthesis, and microbiome in high-fat-induced obesity mice. Before the start of this experiment, obesity groups made obese mice by administering a high-fat diet containing 60% fat for 12 weeks. In the obesity with exercise group, after a high-fat diet for 12 weeks, exercise was performed with high-fat diet for 8 weeks. In the obesity with diet group, a high-fat diet for 12 weeks followed by a normal diet for 8 weeks. Depression and anxiety were determined by open field test and elevated plus maze test. Immunohistochemistry for tryptophan hydroxylase (TPH) in the dorsal raphe, western blot analysis for phosphorylated protein kinase B (p-ATK), total AKT (t-AKT), phosphorylated phosphoinositide 3-kinase (p-PI3K), and total PI3K (t-PI3K) in the hippocampus were performed. Analysis of microbiome was also conducted. Obesity-induced depression and anxiety status, suppressed ratio of p-AKT/t-AKT and p-PI3K/t-PI3K, and inhibited TPH synthesis. Exercise and diet improved depression and anxiety status, activated p-AKT/t-AKT and p-PI3K/t-PI3K, and increased TPH synthesis. Exercise and diet improved depression and anxiety status by increasing the insulin signaling pathway and promoting serotonin production. These effects of exercise and diet were almost similar. In addition, exercise and diet regulated the composition of gut microbiota.

Treadmill Exercise Ameliorates Short-term Memory Impairment by Suppressing Hippocampal Neuroinflammation in Poloxamer-407-Induced Hyperlipidemia Rats.

PURPOSE: Poloxamer-407 (P-407) is used to induce hyperlipidemia. Exercise is effective in improving arteriosclerosis and cognitive impairment. In this research, the effect of treadmill running on short-term memory in the P-407-treated hyperlipidemia rats was studied focusing on neuroinflammation. METHODS: Rats were classified in normal group, normal and treadmill exercise group, P-407-treated group, and P-407-treated and treadmill exercise group. Hyperlipidemia rats were made by single intraperitoneal injection with P-407 (500 mg/kg). Treadmill exercise was conducted for 30 minutes once a day, 5 days per week during 28 days. Step-down avoidance task was done to measure short-term memory. Glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 were assessed by immunohistochemistry. Expression of adhesion molecules and proinflammatory cytokines was determined by western blot analysis. RESULTS: Treadmill exercise alleviated lipid profiles in the P-407-induced hyperlipidemia rats. Treadmill exercise improved short-term memory, inhibited reactive astrogliosis and microglia activation, and suppressed expression of adhesion molecules and proinflammatory cytokines in the hyperlipidemic rats. CONCLUSION: Treadmill exercise exerts alleviating effect on memory deficits by inhibiting hippocampal neuroinflammation in the hyperlipidemia. The current results suggest that treadmill running serves as the treatment strategy for the cognitive dysfunction caused by hyperlipidemia.

Treadmill exercise ameliorates social isolation-induced memory impairment by enhancing silent information regulator-1 expression in rats.

The effect of treadmill exercise on the social isolation-induced memory impairment in relation with the silent information regulator-1 (SIRT-1) was investigated. The rats in the control groups lived four in the stan-dard cages for 8 weeks. The rats in the social isolation groups lived alone in the small cages for 8 weeks. The rats in the treadmill exercise groups were subjected to run on a treadmill for 30 min once a day for 8 weeks. We used step-through avoidance test for short-term memory and Morris water maze task for spatial working memory. Immunohisto-chemistry for SIRT-1 and western blot analysis for Bax, Bcl-2, cleaved caspase-3, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) were performed. The rats in the social isolation group showed a decrease in short-term memory and spatial working memory. Treadmill exercise alleviated short-term memory and spatial working memory in the social isolation rats. SIRT-1 expression in the hippocampus was decreased in the rats of social isolation group. Treadmill exercise increased SIRT-1 expression in the social isolation rats. Bax expression was increased, Bcl-2 expression was decreased, and cleaved caspase-3 expression in the hippocampus was increased in the rats of social isolation group. Treadmill exercise decreased Bax expression, increased Bcl-2 expression, and decreased cleaved caspase-3 expression in the social isolation rats. Hippocampal BDNF and TrkB expression was decreased in the rats of social isolation group. Treadmill exercise increased BDNF and TrkB expression in the social isolation rats.

Treadmill Exercise Improves Motor Function and Short-term Memory by Enhancing Synaptic Plasticity and Neurogenesis in Photothrombotic Stroke Mice.

PURPOSE: Thrombotic stroke is a type of ischemic stroke characterized by motor dysfunction and memory impairments. In the present study, the effect of treadmill exercise on motor function and short-term memory was evaluated in relation with synaptic plasticity in the mice with photothrombotic stroke. METHODS: Photothrombotic stroke was induced by cortical photothrombotic vascular occlusion. The mice in the treadmill exercise groups performed running on a motorized treadmill for 28 days. Motor function was determined using rota-rod test and foot fault test. Step-through avoidance task was conducted to evaluate short-term memory. Immunohistochemistry for 5-bromo-2'-deoxyuridine and doublecortin was conducted to detect new cell generation. Postsynaptic density protein 95, synaptophysin, brain-derived neurotrophic factor (BDNF), and tyrosine kinase B receptor (TrkB) were determined using western blot. The number of dendritic spines was determined using Golgi stain. RESULTS: Treadmill exercise improved motor function and short-term memory in mice with the photothrombotic stroke. The infarct size was reduced and the number of dendritic spines and expression of postsynaptic density protein 95 and synaptophysin in the peri-infarct cortex and hippocampus were increased by treadmill exercise in photothrombotic stroke mice. Treadmill exercise enhanced neurogenesis through increasing the expression of the hippocampal BDNF and TrkB in photothrombotic stroke mice. CONCLUSION: Treadmill exercise improved motor function and short-term memory through increasing synaptic plasticity and neurogenesis in photothrombotic stroke mice. Treadmill exercise can be used as an effective treatment strategy to improve brain function related to stroke.

Treadmill exercise ameliorates memory impairment through ERK-Akt-CREB-BDNF signaling pathway in cerebral ischemia gerbils.

Neuronal cell death in the hippocampus by cerebral ischemia causes disability of memory function. Cerebral ischemia also alters the expressions of brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate-responsive element binding protein (CREB), extracellular signal-regulated protein kinase (ERK), and phosphatidylinositol 3-kinase/protein kinase B (Akt). In the present study, we investigated the effect of treadmill exercise on cerebral ischemia in relation with ERK-Akt-CREB-BDNF signaling pathway in the hippocampus using gerbils. Induction of cerebral ischemia deteriorated short-term memory with suppression of phosphorylation of ERK-Akt-CREB-BDNF pathway in the hippocampus of gerbils. Enhancement of apoptosis in the hippocampus was accompanied in the ischemia gerbils. Treadmill exercise improved short-term memory through enhancing phosphorylation of ERK-Akt-CREB-BDNF pathway with suppressing apoptosis in the hip-pocampus of the ischemia gerbils. The present results suggest that improvement of memory function after cerebral ischemia by treadmill exercise may be involved in the ERK-Akt-CREB-BDNF signaling pathway, resulting in inhibition of apoptosis in the hippocampus.

Global metabolomics analysis of serum from humans at risk of thrombotic stroke.

We aimed to determine the serum concentrations of altered compounds to understand the changes in metabolism and pathophysiology that occur prior to thrombotic stroke. In this prospective cohort study, high-resolution metabolomics (HRM) was employed to analyze serum samples obtained from patients at risk of stroke (n = 99) and non-risk controls (n = 301). Partial least-squares discriminant analysis (PLS-DA), along with univariate analysis using a false discovery rate (FDR) of q = 0.05 were employed to identify the discriminant metabolic profiles and to determine significantly different metabolites between healthy control and stroke risk groups. PLS-DA satisfactorily separated the stroke risk sera from control sera. Additionally, these discriminant metabolic profiles were not related to hypertension, smoking, diabetes mellitus, or insulin sensitivity. A group of 35 metabolites, most of them amino acids, that were capable of discriminating stroke risk sera from controls were identified using untargeted metabolomics. Further, the targeted metabolomics approach confirmed that the quantified concentrations of l-tryptophan, 3-methoxytyramine, methionine, homocysteinesulfinic acid, cysteine, isoleucine, carnitine, arginine, linoleic acid, and sphingosine were specifically elevated in the sera of patients who were later diagnosed with stroke. Our untargeted and targeted metabolomics approaches support investigating these compounds as novel biomarkers for early and non-invasive detection of thrombotic stroke.

Berberine Ameliorates Brain Inflammation in Poloxamer 407-Induced Hyperlipidemic Rats.

PURPOSE: Hyperlipidemia, which promotes the development of atherosclerosis, ischemic stroke, and other forms of brain injury, can be induced by poloxamer-407. Berberine is a primary pharmacological active component of Coptidis Rhizoma that has a number of therapeutic activities. This study investigated the effects of berberine on poloxamer-407-induced brain inflammation by evaluating its effects on short-term memory, cell proliferation, inflammation, and apoptosis in the hippocampus. METHODS: To induce hyperlipidemia in a rat model, 500 mg/kg of poloxamer-407 was injected intraperitoneally. Berberine was orally administered to the rats in the berberine-treated groups once a day for 4 weeks. The step-down task avoidance task was performed to measure short-term memory. An analysis of serum lipids, immunohistochemistry for 5-bromo-2'-deoxyuridine, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1) in the dentate gyrus, and western blot analysis for Bax, Bcl-2, and cytochrome c in the hippocampus were performed. RESULTS: In hyperlipidemic rats, berberine reduced the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol and increased the level of high-density lipoprotein cholesterol in hyperlipidemic rats. Berberine also increased cell proliferation and short-term memory, as well as decreasing the expression of GFAP, Iba1, Bax, and cytochrome c and increasing Bcl-2 expression. CONCLUSION: Berberine treatment improved short-term memory in hyperlipidemia by increasing neuronal proliferation and inhibiting neuronal apoptosis. Berberine treatment also improved lipid metabolism.

Effect of sildenafil citrate on brain central fatigue after exhaustive swimming exercise in rats.

Sildenafil citrate, a potent and selective inhibitor of phosphodiesterase type-5, is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. We investigated the effect of sildenafil citrate on brain central fatigue through serotonin (5-hydroxytryptamine, 5-HT) synthesis after exhaustive swimming exercise in rats. The rats in the sildenafil citrate-treated groups received sildenafil citrate orally once a day for 14 consecutive days at respective dosage. On the 14 days after starting experiment, each animal was submitted to swimming test with intensity equivalent to overload. The exhaustion was defined as a state in which coordinated movements did not return to the water surface for breathing within 10 sec. Immunohistochemistry for 5-HT, tryptophan hydroxylase (TPH), and western blot for serotonergic type 1A (5-HT1A) receptor and 5-HT transporter (5-HTT) were performed. Exhaustive swimming exercise increased 5-HT and TPH expressions in the dorsal raphe and sildenafil citrate suppressed 5-HT and TPH expressions in the exhaustive swimming exercise rats. Exhaustive swimming exercise increased 5-HT1A receptor and 5-HTT expressions in the dorsal raphe and sildenafil citrate suppressed 5-HT1A receptor and 5-HTT expressions in the exhaustive swimming exercise rats. The significant suppressing effect appeared in the 20-mg/kg sildenafil citrate. Sildenafil citrate might be proposed as a potential ergogenic aid through anticentral fatigue.

The effect of cardiac rehabilitation at 4 weeks postoperatively on quality of life in patients treated with totally thoracoscopic ablation.

There is a lack of evidence on the effect of exercise-based cardiac rehabilitation (EBCR) in patients treated with total thoracoscopic ablation (TTA) for atrial fibrillation (AF). Our study investigated the efficacy and safety of postoperative exercise intervention in patients recovering from TTA. Twenty-four patients participated in the study, and were divided into the two groups, exercise group (EG) (n=12) and control group (n= 12). Patients in EG performed the exercise intervention including the aerobic and resistance exercise program twice a week for 8 weeks, which was used as a hospital-based cardiac rehabilitation for the out-patient. A cardiopulmonary exercise test was administered to evaluate aerobic exercise capacity, and qualitative aspect of patient's life was assessed using the Short Form 36 questionnaires to compare pre and postoperative wellness of patient's life. Although there was an increase of VO2peak (peak oxygen uptake) after exercise intervention, no significant improvement was found (P=0.055). Two of 4 physical health scores (role-physical, P=0.013 and general health, P=0.05) and three of four mental health scores (vitality, P=0.027, social function, P=0.016, and mental health, P=0.003) were significantly improved after 8 weeks of EBCR. Each summarized scale in the physical (P=0.022) and mental (P= 0.004) survey section was also significantly improved in postoperative assessment compared to the preoperative one. In this context, we concluded that EBCR initiated at the time point of 4th week after TTA operation can guarantee the secure postoperative physical activity, and the 8 weeks of EBCR can effectively improve the quality of life in AF Patients.

Preischemic treadmill exercise improves short-term memory by inhibiting hypoperfusion-induced disruption of blood-brain barrier after bilateral common carotid arteries occlusion.

Bilateral common carotid arteries occlusion (BCCAO) causes an abrupt reduction of cerebral blood flow, and this method has been used to investigate the effects of chronic cerebral hypoperfusion on vascular dementia and neuronal injuries. Chronic cerebral hypoperfusion leads to functional changes in the hippocampus and then results in a cognitive impairment. We investigated the effect of preischemic treadmill exercise on short-term memory and blood-brain barrier integration following cerebral hypoperfusion caused by BCCAO. The rats in the preischemic treadmill exercise and BCCAO group were made to run on a treadmill for 30 min once a day for 4 weeks. At 4 weeks after performing treadmill exercise, right carotid artery was ligated, and 1 week after, left common carotid artery was ligated. At 20 days after BCCAO, short-term memory was evaluated. Half of the rats were sacrificed 2 days after BCCAO and the other rats were sacrificed at 3 weeks after BCCAO. Immunohistochemistry and western blot were performed. Preischemic treadmill exercise alleviated impairment of short-term memory in the step-down avoidance task. Preischemic treadmill exercise reduced microvascular injury in the hippocampus. Preischemic treadmill exercise prevented the reduction of zonula occludens-1 in the hippocampus and inhibited the activation of matrix metalloproteinase-9. Therefore, pre-conditioning treadmill exercise might be used as a therapeutic strategy for the prevention of stroke in patients.

Treadmill exercise ameliorates nicotine withdrawal-induced symptoms.

Nicotine withdrawal symptoms comprise insomnia, depression, anxiety, attention disorders, and increased craving. We evaluated the ameliorating effect of treadmill exercise on nicotine withdrawal symptoms. The rats in the nicotine withdrawal groups received subcutaneous injection with 6-mg/kg nicotine hydrogen tartrate salt for 17 days. And then, the injection of nicotine hydrogen tartrate salt was stopped next for 2 weeks. The rats in the exercise groups performed treadmill running once a day, 5 days per week, for 31 days. In the present results, activity was decreased and anxiety-like behavior was observed in the nicotine withdrawal rats. Treadmill running increased activity and ameliorated anxiety-like behavior in the nicotine-withdrawal rats. Expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe were decreased in the nicotine withdrawal rats, in contrast, treadmill running increased TPH and 5-HT expressions. Impaired short-term memory and deteriorated spatial learning ability were observed in the nicotine withdrawal rats, in contrast, treadmill running ameliorated impairment of short-term memory and spatial learning ability. Expressions of brain-derived neurotrophic factor and tyrosine kinase B (TrkB) were decreased in the nicotine withdrawal rats, in contrast, treadmill running increased brain-derived neurotrophic factor and TrkB expressions. The numbers of the doublecortin (DCX)-positive cells and 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the dentate gyrus were suppressed in the nicotine withdrawal rats, in contrast, treadmill running enhanced the numbers of DCX-positive cells and BrdU-positive cells. The present study demonstrate that treadmill exercise ameliorated nicotine withdrawal-induced anxiety, depression, and memory impairment.

Exercise Alleviates Cognitive Functions by Enhancing Hippocampal Insulin Signaling and Neuroplasticity in High-Fat Diet-Induced Obesity.

Obesity, caused by a high-fat diet (HFD), leads to insulin resistance, which is a precursor of diabetes and a risk factor for impaired cognitive function, dementia, and brain diseases, such as Alzheimer's disease. Physical exercise has positive effects on obesity and brain functions. We investigated whether the decline in cognitive function caused by a HFD could be improved through exercise by examining insulin signaling pathways and neuroplasticity in the hippocampus. Four-week-old C57BL/6 male mice were fed a HFD or a regular diet for 20 weeks, followed by 12 weeks of treadmill exercise. To ascertain the effects of treadmill exercise on impaired cognitive function caused by obesity, the present study implemented behavioral testing (Morris water maze, step-down). Moreover, insulin-signaling and neuroplasticity were measured in the hippocampus and dentate gyrus. Our results demonstrated that HFD-fed obesity-induced insulin resistance was improved by exercise. In addition, the HFD group showed a decrease in insulin signaling and neuroplasticity in the hippocampus and the dentate gyrus and increased cognitive function impairment, which were reversed by physical exercise. Overall, our findings indicate that physical exercise may act as a non-pharmacologic method that protects against cognitive dysfunction caused by obesity by improving hippocampal insulin signaling and neuroplasticity.

Long-term Surgical and Chemical Castration Deteriorates Memory Function Through Downregulation of PKA/CREB/BDNF and c-Raf/MEK/ERK Pathways in Hippocampus.

PURPOSE: Goserelin is a drug used for chemical castration. In a rat model, we investigated whether surgical and chemical castration affected memory ability through the protein kinase A (PKA)/cyclic adenosine monophosphate response elementbinding protein (CREB)/brain-derived neurotrophic factor (BDNF) and c-Raf/mitogen-activated protein kinases-extracellular signal-regulated kinases (MEK)/extracellular signal-regulated kinases (ERK) pathways in the hippocampus. METHODS: Orchiectomy was performed for surgical castration and goserelin acetate was subcutaneously transplanted into the anterior abdominal wall for chemical castration. Immunohistochemistry was done to quantify neurogenesis. To assess the involvement of the PKA/CREB/BDNF and c-Raf/MEK/ERK pathways in the memory process, western blots were used. RESULTS: The orchiectomy group and the goserelin group showed less neurogenesis and impaired short-term and spatial memory. Phosphorylation of PKA/CREB/BDNF and phosphorylation of c-Raf/MEK/ERK decreased in the orchiectomy and goserelin groups. CONCLUSION: Short-term memory and spatial memory were affected by surgical and chemical castration via the PKA/CREB/BDNF and c-Raf/MEK/ERK signaling pathways.

Wnt signaling pathway is implicated in the alleviating effect of treadmill exercise on maternal separation-induced depression.

Maternal separation in the developmental stage has a negative influence on brain development and causes depression. The extracellular ligand, Wnt, and its receptors play an important role in axis formation and neural development. Exercise inhibits apoptosis, increases cell proliferation, and exerts antidepressive effect. In this study, the effect of treadmill exercise on the maternal separation-induced depression was investigated in the aspect of Wnt signaling pathway. The maternal separation started on the postnatal day 14. The rat pups in the exercise groups were forced to run on a treadmill for 30 min once a day from postnatal day 21 to postnatal day 34. The rat pups in the maternal separation and fluoxetine-treated group were intraperitoneally injected with 5-mg/kg fluoxetine once a day from postnatal day 21 to postnatal day 34. Forced swimming test was performed to evaluate the depression level. Western blotting was performed for the expressions of Wnt signaling ligands, Wnt2 and Wnt3a, and Wnt signaling inhibitors, Dkk1, and sFRP3. Maternal separation showed depressive behaviors in the forced swimming test. Treadmill exercise alleviated depressive behaviors in the maternal separation rat pups. Expressions of Wnt2 and Wnt3a were decreased by maternal separation. Treadmill exercise alleviated maternal separation-induced reduction of Wnt2 and Wnt3a expressions. Expressions of Dkk1 and sFRP3 in the hippocampus were increased by maternal separation. Treadmill exercise alleviated maternal separation-induced reduction of Dkk1 and sFRP3 expressions. Our study demonstrated that treadmill exercise activates Wnt signaling pathway, and then exerted antidepressive effect.

Effects of sildenafil citrate on peripheral fatigue and exercise performance after exhaustive swimming exercise in rats.

Sildenafil citrate is a potent and selective inhibitor of phosphodiesterase type-5 used to treat erectile dysfunction. We investigated the effects of sildenafil citrate treatment on peripheral fatigue and exercise performance after exhaustive swimming exercise in rats. The rats in the sildenafil citrate-treated groups received sildenafil citrate orally once a day for 14 consecutive days at respective dosage. On the 14 days after starting experiment, each animal was submitted to swimming test with intensity equivalent to overload. The exhaustion was defined as a state in which coordinated movements did not return to the water surface for breathing within 10 sec. Western blot for monocarboxylate transporter (MCT)1, MCT4, and neuronal nitric oxide synthase (nNOS) were performed. Exhaustive swimming exercise decreased time of exhaustion and increased lactate concentration, however, sildenafil citrate enhanced time of exhaustion and decreased lactate concentration. Exhaustive swimming exercise increased MCT1 and MCT4 expressions in the gastrocnemius muscles and sildenafil citrate further enhanced MCT1 and MCT4 expressions in the exhaustive swimming exercise rats. Exhaustive swimming exercise decreased nNOS expression in the gastrocnemius muscles and sildenafil citrate enhanced nNOS expression in the exhaustive swimming exercise rats. The most potent effect appeared in the 20-mg/kg sildenafil citrate. Sildenafil citrate might be proposed as a potential ergogenic aid through antiperipheral fatigue.