Upregulation of Dpysl2 and Spna2 gene expression in the rat brain after ischemic stroke

Upregulation of Dpysl2 and Spna2 gene expression in the rat brain after ischemic stroke
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DOI:
10.1016/j.neuint.2009.03.005
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发表时间:
2009-09-01
影响因子:
4.2
通讯作者:
Dheen, S. Thameem
Dheen, S. Thameem
中科院分区:
医学3区
文献类型:
--
作者:
Indraswari, Fransisca;Wong, Peter T. H.;Dheen, S. Thameem

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缺血激活中枢神经系统中潜在的破坏性和保护性蛋白质的合成。二氢嘧啶酶样2 (Dpysl2),一种参与神经元分化和轴突引导的蛋白质,以及a-谱蛋白2 (Spna2),一种参与维持神经元膜完整性的蛋白质,在各种神经系统疾病中被发现发生改变。Dpysl2和Spna2蛋白的修饰在局灶性缺血性脑卒中中已有报道,但其意义尚未确定。因此,本研究旨在研究Dpysl2和Spna2基因在正常和脑卒中大鼠脑中的时间表达,并对脑卒中的细胞面积、凋亡和小胶质细胞进行表征。闭塞大鼠脑大脑中动脉,切片脑组织进行Dpysl2、Spna2基因原位杂交、TUNEL、OX-42免疫荧光染色。实时荧光定量pcr检测Dpysl2和Spna2 mRNA表达。脑凋亡和小胶质细胞的表征显示,凋亡细胞和活化的小胶质细胞主要分布在脑卒中的同侧皮层和纹状体的梗死核心。脑卒中后半影区Dpysl2和Spna2 mRNA表达显著上调主要发生在皮层和纹状体损伤肿胀细胞中。中风脑皮层和纹状体半暗区肥大细胞中Dpysl2和Spna2表达上调,提示早期神经元防御机制涉及活跃的神经元修复、再生和发育,因为已知这些基因参与神经突起的生长和可塑性。2009爱思唯尔有限公司版权所有。
Ischemia activates the synthesis of potentially damaging and protective proteins in the central nervous system. Dihydropyrimidinase-like 2 (Dpysl2), a protein involved in neuronal differentiation and axonal guidance, and a-spectrin 2 (Spna2), a protein involved in maintaining neuronal membrane integrity, were found altered in various nervous system diseases. Modifications of Dpysl2 and Spna2 proteins have been reported in focal ischemic stroke, but their significance is not yet established. Therefore, this study was aimed to investigate the temporal expression of Dpysl2 and Spna2 genes in normal and stroke rat brain and to characterize stroke brains for cell areas, apoptosis, and microglia cells. The middle cerebral artery of rat brain was occluded and the brain tissue was sectioned for in situ hybridization of Dpysl2 and Spna2 genes, TUNEL, and OX-42 immunofluorescence staining. Dpysl2 and Spna2 mRNA expression was quantified by real-time RT-PCR. Characterization of stroke brain for apoptosis and microglia cells showed apoptotic cells and activated microglia, mainly in the infarct core of ipsilateral cortex and striatum of stroke brain. Significant upregulation of Dpysl2 and Spna2 mRNA expression in the penumbra region after stroke was observed predominantly in injured swollen cells in the cortex and striatum. Upregulation of Dpysl2 and Spna2 expression in hypertrophic cells in the penumbra regions of cortex and striatum of stroke brain indicates an early neuronal defense mechanism involving active neuronal repair, regeneration and development, as these genes are known to be involved in neurite outgrowth and plasticity. (C) 2009 Elsevier Ltd. All rights reserved.