[1]袁磊,龚济钦,张海霞,等.KA1亚受体在内质网应激致海马神经元死亡中的作用[J].南方医科大学学报,2015,(02):191.
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KA1亚受体在内质网应激致海马神经元死亡中的作用()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2015年02期
页码:
191
栏目:
出版日期:
2015-03-02

文章信息/Info

Title:
Role of KA1 receptor in excitotoxic neurodegeneration in mouse hippocampus triggered
by kainic acid- or tunicamycin-induced endoplasmic reticulum stress
作者:
袁磊龚济钦张海霞钱诗蕾徐斌曾杰赵娟禹华旭
关键词:
KA1亚受体红藻氨酸衣霉素内质网应激糖尿病脑病海马脑立体定位Bederson体征评分免疫组织化学
Keywords:
KA1 subunit kainate receptor kainic acid tunicamycin endoplasmic reticulum stress diabetic encephalopathyhippocampus brain in stereotaxic bederson score immunohistochemistry
摘要:
目的探究KA1亚受体的表达上调在内质网应激致海马神经元死亡中的作用。方法将70只成年雄性昆明小鼠随机分为
红藻氨酸组(KA组)、衣霉素组(TM)500 μg/ml组、TM1000 μg/ml组和TM2000 μg/ml组,海马内注射KA或不同浓度TM,不同
时间段(1、2、3、4、5、8、12 h)灌注取脑,灌注取脑前进行Bederson体征评分,全脑切片FJB染色和免疫组化分析。结果KA组第
3、4、5、8h和TM2000 μg/ml组第4、5小时,Bederson体征评分表明中枢神经功能出现明显损伤,FJB染色示海马内细胞死亡增
加,免疫组化示KA1和P-eIF2α在海马神经元的表达明显上调(P<0.05)。结论海马内注射KA或TM后结果显示内质网应激中
有KA1的表达,在神经元凋亡过程中膜外受体KA1可能首先接受凋亡信号,并向细胞内传导,引起内质网功能紊乱,诱发内质
网应激,并进一步促使神经元调亡。
Abstract:
Objective To explore the effect of up-regulation of KA1 subunit of the kainate receptor on endoplasmic reticulum
stress (ERS)-induced excitotoxic neurodegeneration in mouse hippocampus. Methods Seventy adult male KM mice were
subjected to microinjections into the hippocampus of kainic acid (KA) or 500, 1000, or 2000 μg/ml tunicamycin (TM). At 1, 2, 3,
4, 5, 8, and 12 h after the injections, the mice were assessed for Bederson scores and sacrificed for FJB staining and
immunofluorescence observation of the brain slices. Results At 3, 4, 5, and 8 h after KA injection and at 4 and 5 h after of 2000
μg/ml TM injection, the mice showed severe central nervous system dysfunction, and FJB staining revealed increased cell
death in the hippocampus, where up-regulated expressions of KA1 receptor and ERS marker P-eIF2α were found by
immunofluorescence staining (P<0.05). Conclusion Microinjection of KA or TM into the hippocampus causes neuronal death
and ERS with up-regulated expression of KA1. In this process of neuronal apoptosis, the membrane receptor KA1 receives the
apoptosis signal and transfers it to the inside of the cells to cause cell endoplasmic reticulum dysfunction and ERS response,
which ultimately leads to neuronal death.
更新日期/Last Update: 1900-01-01