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    05 October 2012, Volume 7 Issue 28 Previous Issue    Next Issue
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    Enteric glia mediate neuronal outgrowth through release of neurotrophic factors
    Christopher R. Hansebout, Caixin Su, Kiran Reddy, Donald Zhang, Cai Jiang, Michel P. Rathbone, Shucui Jiang
    2012, 7 (28):  2165-2175. 
    Abstract ( 215 )   PDF (268KB) ( 899 )   Save

    Previous studies have shown that transplanted enteric glia enhance axonal regeneration, reduce tissue damage, and promote functional recovery following spinal cord injury. However, the mechanisms by which enteric glia mediate these beneficial effects are unknown. Neurotrophic factors can promote neuronal differentiation, survival and neurite extension. We hypothesized that enteric glia may exert their protective effects against spinal cord injury partially through the secretion of neurotrophic factors. In the present study, we demonstrated that primary enteric glia cells release nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor over time with their concentrations reaching approximately 250, 100 and 50 pg/mL of culture medium respectively after 48 hours. The biological relevance of this secretion was assessed by incubating dissociated dorsal root ganglion neuronal cultures in enteric glia-conditioned medium with and/or without neutralizing antibodies to each of these proteins and evaluating the differences in neurite growth. We discovered that conditioned medium enhances neurite outgrowth in dorsal root ganglion neurons. Even though there was no detectable amount of neurotrophin-3 secretion using ELISA analysis, the neurite outgrowth effect can be attenuated by the antibody-mediated neutralization of each of the aforementioned neurotrophic factors. Therefore, enteric glia secrete nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-3 into their surrounding environment in concentrations that can cause a biological effect.

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    Down-regulation of Homer1b/c expression protects cultured neurons after traumatic injury
    Weidong Huang, Xiaobin Liu, Zhou Fei, Yuelin Zhang, Jun Yang
    2012, 7 (28):  2176-2181. 
    Abstract ( 327 )   PDF (256KB) ( 835 )   Save

    Activation of metabotropic glutamate receptor 1a aggravates traumatic brain injury. The constitu-tively expressed protein Homer1b/c participates in delivering and anchoring metabotropic glutamate receptors in neurons. Here, we aimed to verify whether down-regulation of Homer1b/c by RNA in-terference could protect cultured rat cortical neurons from traumatic injury. We showed that 36 hours after transfection of Homer1b/c small interfering RNA, metabotropic glutamate receptor 1a was present only in the neuronal cytoplasm, but not in the dendrites. Calcium fluorescence intensity was also decreased significantly. Moreover, lactate dehydrogenase concentration was significantly decreased in Homer1b/c small interfering RNA-transfected cells compared with that in untrans-fected and control small interfering RNA-transfected cells 24 hours after traumatic neuronal injury. Our findings indicate that down-regulation of Homer1b/c could reduce metabotropic glutamate re-ceptor 1a transfer from the cell body to the dendrite, relieve calcium overload, and protect neurons from traumatic injury.

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    Protein hairy enhancer of split-1 expression during differentiation of muscle-derived stem cells into neuron-like cells
    Mina Huang, Zhanpeng Guo, Kun Liu, Xifan Mei, Shiqiang Fang, Jinhao Zeng, Yansong Wang, Yajiang Yuan
    2012, 7 (28):  2182-2187. 
    Abstract ( 201 )   PDF (221KB) ( 820 )   Save

    Muscle-derived stem cells were isolated from the skeletal muscle of Sprague-Dawley neonatal rats aged 3 days old. Cells at passage 5 were incubated in Dulbecco’s modified Eagle’s medium supplemented with 10% (v/v) fetal bovine serum, 20 μg/L nerve growth factor, 20 μg/L basic fibroblast growth factor and 1% (v/v) penicillin for 6 days. Cells presented with long processes, similar to nerve cells. Connections were formed between cell processes. Immunocytochemical staining with neuron specific enolase verified that cells differentiated into neuron-like cells. Immunofluorescence cytochemistry and western blot results revealed that the expression of protein hairy enhancer of split-1 was significantly reduced. These results indicate that low expression of protein hairy enhancer of split-1 participates in the differentiation of muscle-derived stem cells into neuron-like cells.

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    Telencephalin protects PAJU cells from amyloid beta protein-induced apoptosis by activating the ezrin/radixin/moesin protein family/ phosphatidylinositol-3-kinase/protein kinase B pathway
    Heping Yang, Dapeng Wu, Xiaojie Zhang, Xiang Wang, Yi Peng, Zhiping Hu
    2012, 7 (28):  2189-2198. 
    Abstract ( 245 )   PDF (228KB) ( 912 )   Save

    Telencephalin is a neural glycoprotein that reduces apoptosis induced by amyloid beta protein in the human neural tumor cell line PAJU. In this study, we examined the role of the ezrin/radixin/moesin protein family/phosphatidylinositol-3-kinase/protein kinase B pathway in this process. Western blot analysis demonstrated that telencephalin, phosphorylated ezrin/radixin/moesin and phosphatidyli-nositol-3-kinase/protein kinase B were not expressed in PAJU cells transfected with empty plasmid, while they were expressed in PAJU cells transfected with a telencephalin expression plasmid. After treatment with 1.0 nM amyloid beta protein 42, expression of telencephalin and phosphorylated phosphatidylinositol-3-kinase/protein kinase B in the transfected cells gradually diminished, while levels of phosphorylated ezrin/radixin/moesin increased. In addition, the high levels of telencephalin, phosphorylated ezrin/radixin/moesin and phosphatidylinositol-3-kinase/protein kinase B expression in PAJU cells transfected with a telencephalin expression plasmid could be suppressed by the phosphatidylinositol-3-kinase inhibitor LY294002. These findings indicate that telencephalin acti-vates the ezrin/radixin/moesin family/phosphatidylinositol-3-kinase/protein kinase B pathway and protects PAJU cells from amyloid beta protein-induced apoptosis.

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    Brain cell apoptosis and enhancement of nervous excitability in pregnant rats with high plasma levels of homocysteine
    Jun Wang, Jing Ge, Liu Yang, Haiyan Zhang, Xuli Li, Dan Xue
    2012, 7 (28):  2199-2205. 
    Abstract ( 224 )   PDF (289KB) ( 957 )   Save

    Hyperhomocysteinemia is an important risk factor for preeclampsia-eclampsia. This study established a pregnant rat model of hyperhomocysteinemia, in which blood plasma homocysteine concentrations were twice or three times greater than that of normal pregnant rats. TUNEL revealed an increase in the number of apoptotic cells in the frontal cortex of pregnant rats with hyperhomocysteinemia. In addition, immunohistochemical staining detected activated nuclear factor-κB-positve cells in the frontal cortex. Reverse transcription-PCR detected that mRNA expression of the anti-apoptotic gene bcl-2 diminished in the frontal cortex. In situ hybridization and western blotting revealed that N-methyl-D- aspartate receptor 1 mRNA and protein expression was upregulated in the frontal cortex and hippocampus. These results indicate that hyperhomocysteinemia can induce brain cell apoptosis, increase nerve excitability, and promote the occurrence of preeclampsia in pregnant rats.

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    Microstructural changes in memory and reticular formation neural pathway after simple concussion
    Lin Ouyang, Rongyue Shi, Yuhui Xiao, Jiarong Meng, Yihe Guo, Guangming Lu
    2012, 7 (28):  2206-2212. 
    Abstract ( 224 )   PDF (256KB) ( 847 )   Save

    Patients with concussion often present with temporary disturbance of consciousness. The microstructural and functional changes in the brain associated with concussion, as well as the relationship with transient cognitive disorders, are currently unclear. In the present study, a rabbit model of simple concussion was established. Magnetic resonance-diffusion tensor imaging results revealed that the corona radiata and midbrain exhibited significantly decreased fractional anisotropy values in the neural pathways associated with memory and the reticular formation. In addition, the apparent diffusion coefficient values were significantly increased following injury compared with those before injury. Following a 1-hour period of quiet rest, the fractional anisotropy values significantly increased, and apparent diffusion coefficient values significantly decreased, returning to normal pre-injury levels. In contrast, the fractional anisotropy values and apparent diffusion coefficient values in the corpus callosum, thalamus and hippocampus showed no statistical significant alterations following injury. These findings indicate that the neural pathways associated with memory and the reticular formation pathway exhibit reversible microstructural white matter changes when concussion occurs, and these changes are exhibited to a different extent in different regions.

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    A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats
    Minghua Jin, Peilin Song, Na Li, Xuejun Li, Jiajun Chen
    2012, 7 (28):  2213-2220. 
    Abstract ( 207 )   PDF (231KB) ( 998 )   Save

    Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poi-soning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our ex-perimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and dem-onstrated that the poisoning was dose-dependent.

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    Expression of Clock genes in the pineal glands of newborn rats with hypoxic-ischemic encephalopathy
    Bin Sun, Xing Feng, Xin Ding, Li Bao, Yongfu Li, Jun He, Meifang Jin
    2012, 7 (28):  2221-2226. 
    Abstract ( 219 )   PDF (176KB) ( 794 )   Save

    Clock genes are involved in circadian rhythm regulation, and surviving newborns with hypoxic-ischemic encephalopathy may present with sleep-wake cycle reversal. This study aimed to determine the expression of the clock genes Clock and Bmal1, in the pineal gland of rats with hypoxic-ischemic brain damage. Results showed that levels of Clock mRNA were not significantly changed within 48 hours after cerebral hypoxia and ischemia. Expression levels of CLOCK and BMAL1 protein were significantly higher after 48 hours. The levels of Bmal1 mRNA reached a peak at 36 hours, but were significantly reduced at 48 hours. Experimental findings indicate that Clock and Bmal1 genes were indeed expressed in the pineal glands of neonatal rats. At the initial stage (within 36 hours) of hypoxic-ischemic brain damage, only slight changes in the expression levels of these two genes were detected, followed by significant changes at 36-48 hours. These changes may be associated with circadian rhythm disorder induced by hypoxic-ischemic brain damage.

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    Could androgens maintain specific domains of mental health in aging men by preserving hippocampal neurogenesis?
    Mark I Ransome
    2012, 7 (28):  2227-2239. 
    Abstract ( 310 )   PDF (223KB) ( 1027 )   Save

    Interest surrounds the role of sex-hormones in regulating brain function outside of reproductive behaviour. Declining androgen production in aging males has been associated with cognitive impairment, depression and increased risk of developing Alzheimer's disease. Indication for testosterone replacement therapy is based on biochemically determined low circulating testosterone combined with manifest symptoms. However, which aspects of age-related cognitive decline are attributable to low circulating testosterone remain ambiguous. Studies examining cognition in aging men receiving testosterone replacement therapy have yielded equivocal results. The exact role of testosterone in maintaining cognitive function and the underlying neural mechanisms are largely unknown, though it would appear to be domain specific. Clarity in this area will provide clinical direction toward addressing an increasing healthcare burden of mental health decline coincident with increasing longevity. The premise that androgens contribute to maintaining aspects of mental health in aging men by preserving hippocampal neurogenesis will be used as a forum in this review to discuss current knowledge and the need for further studies to better define testosterone replacement strategies for aging male health.

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