Characterization of neuronal and astroglial responses to ER stress in the hippocampal CA1 area in mice following transient forebrain ischemia
Characterization of neuronal and astroglial responses to ER stress in the hippocampal CA1 area in mice following transient forebrain ischemia
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DOI：
10.1016/j.neuint.2010.03.017
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发表时间：
2010-08-01
影响因子：
4.2
通讯作者：
Ito, Yoshihisa
中科院分区：
文献类型：
--
作者：
Osada, Nobuhiro;Kosuge, Yasuhiro;Ito, Yoshihisa
暂时性前脑缺血已被证明会导致小鼠海马CA 1区的神经元损伤。除了神经元损伤，CA 1区的星形胶质细胞在缺血条件下发生凋亡。虽然受损的星形胶质细胞不能摄取谷氨酸被认为是脑缺血的发病机制，但这种现象背后的分子机制仍未被探索。在本研究中，我们研究了神经元和星形胶质细胞对内质网（ER）应激的反应，内质网应激是小鼠海马短暂性前脑缺血的重要后遗症。再灌注72 h后海马CA 1区细胞损伤明显，部分胶质细胞和神经元ssDNA阳性。增加78 kDa葡萄糖调节蛋白（GRP 78），ER应激的指标，检测到锥体神经元和星形胶质细胞在这方面的损伤后。免疫组化结果显示，caspase-12在锥体外系细胞层的锥体神经元和星形胶质细胞中表达增加。C/EBP同源蛋白（CHOP）的免疫反应性在锥体细胞中显著增加，而在星形胶质细胞中不显著。这些结果表明，星形胶质细胞以及锥体神经元在CA 1区缺血后通过ER应激依赖机制进行凋亡。与神经元凋亡的情况不同。CHOP在星形胶质细胞的细胞死亡中不起作用。(C)2010爱思唯尔有限公司保留所有权利。
Transient forebrain ischemia has been shown to cause neuronal injury in the CA1 area of the hippocampus in mice. In addition to neuronal injury, astrocytes in area CA1 undergo apoptosis under ischemic conditions. Although failure of impaired astrocytes to take up glutamate is thought to contribute to the pathogenesis of cerebral ischemia, the molecular mechanism underlying this phenomenon remains unexplored. In the present study, we investigated neuronal and astroglial responses to endoplasmic reticulum (ER) stress, which is an important sequela of transient forebrain ischemia in the hippocampus of mice. Cellular injury was observed in area CA1 of the hippocampus 72 h after reperfusion, and ssDNA positivity was detectable in some glial cells as well as neurons in this area. An increase of 78-kDa glucose-regulated protein (GRP78), an indicator of ER stress, was detected in pyramidal neurons and astrocytes in this area after the insult. Immunohistochemical analysis showed that caspase-12 was increased in pyramidal neurons and astrocytes located in the extrapyramidal cell layer. Immunoreactivity for C/EBP homologous protein (CHOP) was increased significantly in pyramidal cells but not in astrocytes. These results suggest that astrocytes as well as pyramidal neurons in area CA1 undergo apoptosis through an ER stress-dependent mechanism after ischemia. Unlike the situation in neuronal apoptosis. CHOP does not play a role in the cell death of astrocytes. (C) 2010 Elsevier Ltd. All rights reserved.