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

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.

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

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.

Berberine Ameliorates Brain Inflammation in Poloxamer 407-Induced Hyperlipidemic Rats / 대한배뇨장애요실금학회지

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.

Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway / 대한배뇨장애요실금학회지

PURPOSE: Berberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the hippocampus using gerbils. METHODS: Gerbils received berberine orally once a day for 14 consecutive days, starting one day after surgery. In this study, a step-down avoidance task was used to assess short-term memory. Furthermore, we employed the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate DNA fragmentation, immunohistochemistry to investigate glial fibriallary acidic protein, CD11b, and caspase-3, and western blot to assess PI3K, Akt, Bax, Bcl-2, and cytochrome c. RESULTS: Our results revealed that berberine treatment alleviated ischemia-induced short-term memory impairment. Treatment with berbeine also attenuated ischemia-induced apoptosis and inhibited reactive astrogliosis and microglia activation. Furthermore, berberine enhanced phospho-PI3K and phospho-Akt expression in the hippocampus of ischemic gerbils. CONCLUSIONS: Berberine exerted a neuroprotective effect against ischemic insult by inhibiting neuronal apoptosis via activation of the PI3K/Akt signaling pathway. The antiapoptotic effect of berberine was achieved through inhibition of reactive astrogliosis and microglia activation. Berberine may therefore serve as a therapeutic agent for stroke-induced neurourological problems.

A comparison of brain activity between healthy subjects and stroke patients on fMRI by acupuncture stimulation / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate brain activity patterns during acupuncture in stroke patients, and to compare the result with normal subjects using functional magnetic resonance imaging (fMRI).</p><p><b>METHODS</b>A total of 11 stroke patients with motor weakness and 10 healthy subjects were studied. fMRI was performed during acupuncture on the left side at points Quchi (LI11) and Zusanli (ST36). Data were analyzed using statistical parametric maps of brain activation induced by acupuncture stimulation.</p><p><b>RESULTS</b>The results showed that stimulation of both LI11 and ST36 produced significantly different brain activation patterns between the two groups. The normal group showed a greater overall activation than the stroke group. In the normal group, parts of the frontal lobe, parietal lobe, sub-lobar, cerebellum and midbrain regions were activated by acupuncture at the left LI11. On the other hand, only the right side of the inferior parietal lobule region was activated in the stroke patients. When the left ST36 was stimulated in the normal group, both sides of the frontal lobe, parietal lobe, temporal lobe, and sub-lobar, and the left side of occipital lobe, and the right side of cerebellum and midbrain regions were activated. For the same stimulation in the stroke group, only both sides of the inferior parietal lobule and cerebellum regions were activated (P<0.05, cluster level). Deactivation pattern was not noted during any acupuncture stimulation in both groups.</p><p><b>CONCLUSION</b>Brain signal activations during the same acupuncture were different between the healthy and the stroke patients, and the effects showed a correlation of different acupuncture points.</p>

The Polymorphisms of PPAR-gamma Coactivator 1alpha Gly482Ser (PGC-1alpha Gly482Ser) are Associated with the Nephropathy of Korean Patients with Type 2 Diabetes Mellitus / 대한신장학회잡지

BACKGROUND: We investigated the effects of the common polymorphisms in the peroxisome proliferator- activated receptor gamma2 (PPAR-gamma2 Pro12Ala) and in PPAR-gamma coactivator 1alpha (PGC-1alpha Gly482Ser) genes on the association with the nephropathy of Korean patients with type 2 diabetes mellitus. METHODS: A total of 113 patients with type 2 diabetes and 123 patients with diabetic nephropathy were enrolled in this study. The Pro12Ala polymorphism of the PPAR-gamma2 gene and the Gly482Ser polymorphism in the PGC-1alpha gene were determined with the polymerase chain reaction amplification, BstU-I and Msp I enzyme digestion, and gel electrophoresis. RESULTS: The genotype and allelic frequency of PPAR-gamma2 Pro12Ala gene were not different statistically between the diabetic nephropathy and the control. The genotype of PGC-1alpha Gly482Ser in diabetic nephropathy was also not different from those in control. The allelic frequency and carriage rate of Ser allele in PGC-1alpha Gly482Ser were significantly higher in patients with diabetic nephropathy than those in control (respectively, p<0.05). CONCLUSION: The polymorphisms of the PGC-1alpha Gly482Ser gene are significantly associated with the nephropathy in Korean patients with type 2 diabetes mellitus.

The Polymorphisms of PPAR-gamma Coactivator 1alpha Gly482Ser (PGC-1alpha Gly482Ser) are Associated with the Nephropathy of Korean Patients with Type 2 Diabetes Mellitus / 대한신장학회잡지

BACKGROUND: We investigated the effects of the common polymorphisms in the peroxisome proliferator- activated receptor gamma2 (PPAR-gamma2 Pro12Ala) and in PPAR-gamma coactivator 1alpha (PGC-1alpha Gly482Ser) genes on the association with the nephropathy of Korean patients with type 2 diabetes mellitus. METHODS: A total of 113 patients with type 2 diabetes and 123 patients with diabetic nephropathy were enrolled in this study. The Pro12Ala polymorphism of the PPAR-gamma2 gene and the Gly482Ser polymorphism in the PGC-1alpha gene were determined with the polymerase chain reaction amplification, BstU-I and Msp I enzyme digestion, and gel electrophoresis. RESULTS: The genotype and allelic frequency of PPAR-gamma2 Pro12Ala gene were not different statistically between the diabetic nephropathy and the control. The genotype of PGC-1alpha Gly482Ser in diabetic nephropathy was also not different from those in control. The allelic frequency and carriage rate of Ser allele in PGC-1alpha Gly482Ser were significantly higher in patients with diabetic nephropathy than those in control (respectively, p<0.05). CONCLUSION: The polymorphisms of the PGC-1alpha Gly482Ser gene are significantly associated with the nephropathy in Korean patients with type 2 diabetes mellitus.