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    05 May 2012, Volume 7 Issue 13 Previous Issue    Next Issue
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    Actin-binding Rho activating protein is expressed in the central nervous system of normal adult rats
    Lihua Liu, Mingying Luo, Baolin Yang, Xiaoqiong Wu, Wu Zhu, Yinglu Guan, Weijun Cai,Kerstin Troidl, Wolfgang Schaper, Jutta Schaper
    2012, 7 (13):  965-970. 
    Abstract ( 268 )   PDF (376KB) ( 887 )   Save

    Previous studies show that actin-binding Rho activating protein (Abra) is expressed in cardiomyocytes and vascular smooth muscle cells. In this study, we investigated the expression profile of Abra in the central nervous system of normal adult rats by confocal immunofluorescence. Results showed that Abra immunostaining was located in neuronal nuclei, cytoplasm and processes in the central nervous system, with the strongest staining in the nuclei; in the cerebral cortex, Abra positive neuronal bodies and processes were distributed in six cortical layers including molecular layer, external granular layer, external pyramidal layer, internal granular layer, internal pyramidal layer and polymorphic layer; in the hippocampus, the cell bodies of Abra positive neurons were distributed evenly in pyramidal layer and granular layer, with positive processes in molecular layer and orien layer; in the cerebellar cortex, Abra staining showed the positive neuronal cell bodies in Purkinje cell layer and granular layer and positive processes in molecular layer; in the spinal cord,Abra-immunopositive products covered the whole gray matter and white matter; co-localization studies showed that Abra was co-stained with F-actin in neuronal cytoplasm and processes, but weakly in the nuclei. In addition, in the hippocampus, Abra was co-stained with F-actin only in neuronal processes, but not in the cell body. This study for the first time presents a comprehensive overview of Abra expression in the central nervous system, providing insights for further investigating the role of Abra in the mature central nervous system.

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    Methyl 3,4-dihydroxybenzoate promotes neurite outgrowth of cortical neurons cultured in vitro
    Zheng Zhang, Xing Zhou, Xiaowen Zhou, Xiao Xu, Minjing Liao, Li Yan, Ruohua Lv,Huanmin Luo
    2012, 7 (13):  971-977. 
    Abstract ( 218 )   PDF (150KB) ( 1055 )   Save

    Cerebral cortical neurons from neonatal rats were cultured in the presence of methyl 3,4-dihydroxybenzoate (MDHB; 2, 4, and 8 μM). Results showed that MDHB significantly promoted neurite outgrowth and microtubule-associated protein 2 mRNA expression, and increased neuronal survival in a dose-dependent manner. Moreover, MDHB induced brain-derived neurotrophic factor expression. These findings suggest that MDHB has a neurotrophic effect, which may be due to its ability to increase brain-derived neurotrophic factor expression.

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    Intracerebroventricular transplanted bone marrow stem cells survive and migrate into the brain of rats with Parkinson’s disease
    Ping Gu, Zhongxia Zhang, Dongsheng Cui, Yanyong Wang, Lin Ma, Yuan Geng,Mingwei Wang
    2012, 7 (13):  978-984. 
    Abstract ( 269 )   PDF (145KB) ( 868 )   Save

    In this study, 6-hydroxydopamine was stereotaxically injected into the right substantia nigra compact and ventral tegmental area of rats to establish Parkinson’s disease models. The rats then received a transplantation of bone marrow stromal cells that were previously isolated, cultured and labeled with 5-bromo-2’-deoxyuridine in vitro. Transplantation of the bone marrow stromal cells significantly decreased apomorphine-induced rotation time and the escape latency in the Morris water maze test as compared with rats with untreated Parkinson’s disease. Immunohistochemical staining showed that, 5-bromo-2’-deoxyuridine-immunoreactive cells were present in the lateral ventricular wall and the choroid plexus 1 day after transplantation. These immunoreactive cells migrated to the surrounding areas of the lateral cerebral ventricle along the corpus callosum. The results indicated that bone marrow stromal cells could migrate to tissues surround the cerebral ventricle via the cerebrospinal fluid circulation and fuse with cells in the brain, thus altering the phenotype of cells or forming neuron-like cells or astrocytes capable of expressing neuron-specific proteins. Taken together, the present findings indicate that bone marrow stromal cells transplanted intracerebroventricularly could survive, migrate and significantly improve the rotational behavior and cognitive function of rats with experimentally induced Parkinson’s disease.

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    Isolation, cultivation and identification of brain glioma stem cells by magnetic bead sorting
    Xiuping Zhou, Chao Zheng4, Qiong Shi, Xiang Li, Zhigang Shen, Rutong Yu
    2012, 7 (13):  985-992. 
    Abstract ( 191 )   PDF (440KB) ( 1222 )   Save

    This study describes a detailed process for obtaining brain glioma stem cells from freshly dissected human brain glioma samples using an immunomagnetic bead technique combined with serum-free media pressure screening. Furthermore, the proliferation, differentiation and self-renewal biological features of brain glioma stem cells were identified. Results showed that a small number of CD133 positive tumor cells isolated from brain glioma samples survived as a cell suspension in serum-free media and proliferated. Subcultured CD133 positive cells maintained a potent self-renewal and proliferative ability, and expressed the stem cell-specific markers CD133 and nestin. After incubation with fetal bovine serum, the number of glial fibrillary acidic protein and microtubule associated protein 2 positive cells increased significantly, indicating that the cultured brain glioma stem cells can differentiate into astrocytes and neurons. Western blot analysis showed that tumor suppressor phosphatase and tensin homolog was highly expressed in tumor spheres compared with the differentiated tumor cells. These experimental findings indicate that the immunomagnetic beads technique is a useful method to obtain brain glioma stem cells from human brain tumors.

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    Melatonin combined with exercise cannot alleviate cerebral injury in a rat model of focal cerebral ischemia/reperfusion injury
    Seunghoon Lee, Jinhee Shin, Minkyung Lee, Yunkyung Hong, Sang-Kil Lee, Youngjeon Lee1,Tserentogtokh Lkhagvasuren, Dong-Wook Kim, Young-Ae Yang, Kyu-Tae Chang,Yonggeun Hong
    2012, 7 (13):  993-999. 
    Abstract ( 221 )   PDF (218KB) ( 1030 )   Save

    Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone.Hypoxia-inducible factor 1α mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 (NG2)mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage.

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    Increased expression of receptor for advanced glycation end-products worsens focal brain ischemia in diabetic rats
    Ying Xing, Jinting He, Weidong Yu, Lingling Hou, Jiajun Chen
    2012, 7 (13):  1000-1005. 
    Abstract ( 188 )   PDF (142KB) ( 1135 )   Save

    A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression, and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Additionally, phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups. Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats. The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase, thereby worsening brain injury associated with focal brain ischemia in diabetic rats.

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    Paroxetine engenders analgesic effects through inhibition of p38 phosphorylation in a rat migraine model
    Chuanming Wang, Wei Bi, Yanran Liang, Xiuna Jing, Songhua Xiao, Yannan Fang,Qiaoyun Shi, Enxiang Tao
    2012, 7 (13):  1006-1012. 
    Abstract ( 213 )   PDF (204KB) ( 711 )   Save

    In this study, a model of migraine was established by electrical stimulation of the superior sagittal sinus in rats. These rats were then treated orally with paroxetine at doses of 2.5, 5, or 10 mg/kg per day for 14 days. Following treatment, mechanical withdrawal thresholds were significantly higher,extracellular concentrations of 5-hydroxytryptamine in the periaqueductal grey matter and nucleus reticularis gigantocellularis were higher, and the expression of phosphorylated p38 in the trigeminal nucleus caudalis was lower. Our experimental findings suggest that paroxetine has analgesic effects in a rat migraine model, which are mediated by inhibition of p38 phosphorylation.

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    Survivin-specific small interfering RNAs enhance sensitivity of glioma U-87MG cells to paclitaxel by promoting apoptosis
    Yunliang Xie, Yanbo Liu, Weigao Shen, Bo Zhang, Qun Liu
    2012, 7 (13):  1013-1019. 
    Abstract ( 169 )   PDF (155KB) ( 793 )   Save

    A survivin siRNA expression vector was transfected into glioma U-87MG cells and these cells were then treated with paclitaxel. The results showed that survivin-specific siRNA combined with paclitaxel treatment synergistically inhibited glioma U-87MG cell proliferation and promoted apoptosis. This treatment also inhibited the expression of the cell cycle regulatory proteins, survivin,cyclinD1, c-Myc and CDK4 and enhanced the sensitivity of U-87MG cells to paclitaxel.

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    Histone acetylation of the htr3a gene in the prefrontal cortex of Wistar rats regulates ethanol-seeking behavior
    Yahui Xu, Xuebing Liu, Xiaojie Zhang, Guanbai Zhang, Ruiling Zhang, Tieqiao Liu, Wei Hao
    2012, 7 (13):  1021-1028. 
    Abstract ( 209 )   PDF (104KB) ( 767 )   Save

    Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol-seeking behavior. However, the effects of a histone deacetylase inhibitor on ethanol-seeking behavior and epigenetic regulation of htr3a mRNA expression after chronic ethanol exposure are not fully understood. Using quantitative reverse transcription-polymerase chain reaction and chromatin immunoprecipitation analysis, we investigated the effects of chronic ethanol exposure and its interaction with a histone deacetylase inhibitor on histone-acetylation-mediated changes in htr3a mRNA expression in the htr3a promoter region. The conditioned place preference procedure was used to evaluate ethanol-seeking behavior. Chronic exposure to ethanol effectively elicited place conditioning. In the prefrontal cortex, the acetylation of H3K9 and htr3a mRNA expression in the htr3a promoter region were significantly higher in the ethanol group than in the saline group. The histone deacetylase inhibitor sodium butyrate potentiated the effects of ethanol on htr3a mRNA expression and enhanced ethanol-induced conditioned place preferences. These results suggest that ethanol upregulates htr3a levels through mechanisms involving H3K9 acetylation, and that histone acetylation may be a therapeutic target for treating ethanol abuse.

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    Tolerance effects of non-steroidal anti-inflammatory drugs microinjected into central amygdala,periaqueductal grey, and nucleus raphe
    Merab G. Tsagareli, Nana Tsiklauri, Ivliane Nozadze, Gulnaz Gurtskaia
    2012, 7 (13):  1029-1039. 
    Abstract ( 202 )   PDF (369KB) ( 811 )   Save

    Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (NSAIDs), or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic (intraperitoneal) administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.

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