Increased vulnerability of hippocampal pyramidal neurons to the toxicity of kainic acid in OASIS-deficient mice
Increased vulnerability of hippocampal pyramidal neurons to the toxicity of kainic acid in OASIS-deficient mice
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DOI：
10.1111/j.1471-4159.2009.06188.x
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发表时间：
2009-08-01
影响因子：
4.7
通讯作者：
Imaizumi, Kazunori
中科院分区：
文献类型：
--
作者：
Chihara, Kazuyasu;Saito, Atsushi;Imaizumi, Kazunori
内质网（ER）应激反应是一种防御系统，用于处理内质网管内未折叠蛋白的积累。已知年老星形胶质细胞特异性诱导物质（OASIS）在星形胶质细胞中表达并参与内质网应激反应；然而，OASIS在受损大脑中的功能尚不清楚。在这项研究中，我们研究了OASIS在腹腔注射kainic酸（KA）小鼠海马神经元变性中的作用。KA对OASIS mRNA有较强的诱导作用，其时间过程与ER分子伴侣免疫球蛋白重链结合蛋白mRNA的诱导过程相似。原位杂交表明，KA注射液可诱导免疫球蛋白重链结合蛋白mRNA在胶质原纤维酸性蛋白阳性星形胶质细胞和锥体神经元中表达，而OASIS mRNA仅在胶质原纤维酸性蛋白阳性星形胶质细胞中表达上调。原代培养的星形胶质细胞，而不是OASIS-/-小鼠的神经元，显示出对内质网应激的易感性降低。与野生型小鼠相比，OASIS-/-小鼠海马锥体神经元对KA的毒性更敏感。综上所述，这些数据表明星形胶质细胞中表达的OASIS对KA诱导的神经元损伤具有重要的保护作用。
The endoplasmic reticulum (ER) stress response is a defense system for dealing with the accumulation of unfolded proteins in the ER lumen. Old astrocyte specifically induced substance (OASIS) is known to be expressed in astrocytes and involved in the ER stress response; however the function of OASIS in the injured brain has remained unclear. In this study, we examined the roles of OASIS in neuronal degeneration in the hippocampi of mice intraperitoneally injected with kainic acid (KA). OASIS mRNA was strongly induced in response to KA injection, with a similar time course to the induction of ER molecular chaperone immunoglobulin heavy chain binding protein mRNA. In situ hybridization showed that KA injection causes induction of immunoglobulin heavy chain binding protein mRNA in glial fibrillary acidic protein-positive astrocytes as well as in pyramidal neurons, although up-regulation of OASIS mRNA was only detected in glial fibrillary acidic protein-positive astrocytes. Primary cultured astrocytes, but not the neurons of OASIS-/- mice, revealed reduced vulnerability to ER stress. Furthermore, pyramidal neurons in the hippocampi of OASIS-/- mice were more susceptible to the toxicity induced by KA than those of wild-type mice. Taken together, these data suggest that OASIS expressed in astrocytes plays important roles in protection against the neuronal damage induced by KA.