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Purpose@#Wnt pathway is closely related to neurodevelopmental process associated with cognitive function. After administration of valproic acid to the pregnant mice, the effect of swimming exercise of pregnant mice on the memory, neuronal production, and apoptosis of pups was studied in relation with Wnt/β-catenin signaling pathway. @*Methods@#On day 12 of pregnancy, mice were injected subcutaneously with 400-mg/kg valproic acid. The pregnant mice in the control with swimming exercise group and in the valproic acid injection with swimming exercise group were allowed for swimming for 30 minutes one time per a day, repeated 5 days per a week, during 3 weeks. Step-through avoidance task and Morris water maze task for memory function, immunohistochemistry for 5-bromo-2’-deoxyuridine (BrdU)-positive cells and western blot for brain-derived neurotrophic factor (BDNF), Wnt, β-catenin, Bcl-2 related X protein (Bax), B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 were carried out. @*Results@#Maternal swimming exercise during pregnancy improved memory function, increased BDNF expression, and neuronal proliferation in the valproic acid injected pups. Maternal swimming exercise during pregnancy suppressed Wnt expression and phosphorylation of β-catenin in the valproic acid injected pups. Maternal swimming exercise inhibited Bax and cleaved caspase-3 expression and increased Bcl-2 expression in the valproic acid injected pups. @*Conclusions@#Maternal swimming exercise during pregnancy improved memory function by increasing cell proliferation and inhibiting apoptosis through Wnt/β-catenin signaling cascade activation in the valproic acid injected pups. Maternal swimming exercise during pregnancy may have a protective effect on factors that induce autism in the fetus.
ABSTRACT
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. @*Conclusions@#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.
ABSTRACT
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. @*Conclusions@#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.
ABSTRACT
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.@*CONCLUSIONS@#Berberine treatment improved short-term memory in hyperlipidemia by increasing neuronal proliferation and inhibiting neuronal apoptosis. Berberine treatment also improved lipid metabolism.
ABSTRACT
PURPOSE@#Chemotherapy is associated with the side effects including damage to the mitochondrial DNA. Doxorubicin (DOX) serves as a chemotherapeutic agent for the patients with breast cancer or prostate cancer. DOX causes muscle weakness and fatigue. We investigated the effects of treadmill exercise on DOX-induced apoptosis and mitochondrial dysfunction in relation to central fatigue. For this study, we used the rat model of DOX-induced muscle damage.@*METHODS@#DOX (2 mg/kg) was intraperitoneally injected 1 time per week for 4 weeks. Treadmill running continued 5 days per week for 4 weeks. Muscle strength and fatigue index in the gastrocnemius were measured. Immunohistochemistry for the expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe was conducted. We used western blot analysis for the expressions of Bax, Bcl-2, and caspases-3 in the gastrocnemius. Mitochondrial function in the gastrocnemius was also evaluated.@*RESULTS@#DOX treatment decreased muscle strength with increase of fatigue index in the gastrocnemius. Mitochondria function was deteriorated and apoptosis in the gastrocnemius was enhanced by DOX treatment. Expressions of TPH and 5-HT in the dorsal raphe were increased by DOX treatment. Treadmill exercise attenuated DOX-induced muscle fatigue and impairment of mitochondria function. Apoptosis in the gastrocnemius was inhibited and over-expression of TPH and 5-HT was suppressed by treadmill exercise.@*CONCLUSIONS@#Apoptosis was enhanced and mitochondria function was deteriorated by DOX treatment, resulting in muscle weakness and central fatigue. Treadmill exercise suppressed apoptosis and prevented deterioration of mitochondria function in muscle, resulting in alleviation of muscle weakness and central fatigue during DOX therapy.
ABSTRACT
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 element-binding 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. CONCLUSIONS: 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.
Subject(s)
Abdominal Wall , Adenosine Monophosphate , Blotting, Western , Castration , Cyclic AMP-Dependent Protein Kinases , Down-Regulation , Goserelin , Hippocampus , Immunohistochemistry , Memory , Memory, Short-Term , Models, Animal , Neurogenesis , Orchiectomy , Phosphorylation , Phosphotransferases , Spatial MemoryABSTRACT
PURPOSE: Rotenone is the most widely used neurotoxin for the making Parkinson disease (PD) animal model. The neurodegenerative disorder PD shows symptoms, such as slowness of movements, tremor at resting, rigidity, disturbance of gait, and instability of posture. We investigated whether treadmill running improves motor ability using rotenone-caused PD rats. The effect of treadmill running on PD was also assessed in relation with apoptosis of cerebellar Purkinje cells. METHODS: Treadmill running was applied to the rats in the exercise groups for 30 minutes once a day for 4 weeks, starting 4 weeks after birth. We used rota-rod test for the determination of motor coordination and balance. In this experiment, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, immunohistochemistry for calbindin, glial fibrillary acidic protein (GFAP), Iba-1, and western blot analysis for Bax and Bcl-2 were performed. RESULTS: Treadmill running enhanced motor balance and coordination by preventing the loss of Purkinje cells in the cerebellar vermis. Treadmill running suppressed PD-induced expression of GFAP-positive reactive astrocytes and Iba-1-positive microglia, showing that treadmill running suppressed reactive astrogliosis and microglia activation. Treadmill running suppressed TUNEL-positive cell number and Bax expression and enhanced Bcl-2 expression, demonstrating that treadmill running inhibited the progress of apoptosis in the cerebellum of rotenone-induced PD rats. CONCLUSIONS: Treadmill running improved motor ability of the rotenone-induced PD rats by inhibiting apoptosis in the cerebellum. Apoptosis suppressing effect of treadmill running on rotenone-induced PD was achieved via suppression of reactive astrocyte and inhibition of microglial activation.