Chinese Journal of Tissue Engineering Research ›› 2014, Vol. 18 ›› Issue (36): 5861-5867.doi: 10.3969/j.issn.2095-4344.2014.36.021

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Kainic acid-induced endoplasmic reticulum stress model

Yuan Lei1, Zhang Hai-xia1, Qian Shi-lei1, Xu Bin1, Gong Ji-qin1, Liu Xiang-hua2, Tang Yuan1, Yu Hua-xu2, 3   

  1. 1First Clinical College of Changsha Medical University, Changsha 410219, Hunan Province, China
    2First Affiliated Hospital of Changsha Medical University, Changsha 410219, Hunan Province, China
    3Changsha Medical University, Key Disciplines in Hunan Province, Changsha 410219, Hunan Province, China
  • Revised:2014-06-03 Online:2014-08-30 Published:2014-08-30
  • Contact: Yu Hua-xu, M.D., Associate professor, First Affiliated Hospital of Changsha Medical University, Changsha 410219, Hunan Province, China; Changsha Medical University, Key Disciplines in Hunan Province, Changsha 410219, Hunan Province, China
  • About author:Yuan Lei, First Clinical College of Changsha Medical University, Changsha 410219, Hunan Province, China Zhang Hai-xia, First Clinical College of Changsha Medical University, Changsha 410219, Hunan Province, China Yuan Lei and Zhang Hai-xia contributed equally to this work.
  • Supported by:

    the National Natural Science Foundation of China, No. 81171136; University Students Research and Innovative Pilot Project of Hunan Province Education Department, No. [2013]191-431 and No. [2012]402-445; the Natural Science Research Projects of Education Department of Hunan Province, No. 10A013; Key Subject Construction Project of Hunan Province, No. [2011]76

Abstract:

BACKGROUND: Previous studies have shown that kainic acid injected into hippocampus can significantly upregulate the expression of excitatory KA1 subunit of the kainate receptor in the hippocampus, and endoplasmic reticulum stress markers, phosphorylation of the alpha subunit of eukaryotic initiation factor 2, accompanied by cell death.
OBJECTIVE: To explore the mechanism of endoplasmic reticulum stress after kainic acid is injected into the hippocampus.
METHODS: 0.15 nmol kainic acid was injected into the hippocampal CA1 region of 32 adult male Kunming mice, the injection time was 60 seconds. At different time points (1, 2, 3, 4, 5, 6, 8 and 12 hours) after kainic acid was injected, the Bederson score analysis was performed, and then the brain was harvested after cerebral perfusion. FJB staining of brain sections and immunofluorescence double labeled observation were also performed.
RESULTS AND CONCLUSION: (1) At 3, 4, 5, 6, 8 hours after kainic acid injection, Bederson score showed severe injury of central nervous system function, and FJB staining showed the increased of cell death in the hippocampus (P < 0.05); At 1, 2, 12 hours after injection, Bederson score showed no obvious injury of central nervous system function, and FJB staining showed unobvious cell death in the hippocampus (P > 0.05). (2) According to the results of FJB staining, the brain sections were selected at 3, 8 hours for immunohistochemistry. The expressionlevels of KA1 receptors and endoplasmic reticulum stress marker P-eIF2α were up-regulated at the same time after kainic acid was injected into hippocampus. Two single-staining KA1 and P-eIF2α immunofluorescence images were synthesized into one over-lapped double-stained image, and two images overlapped, indicating that the up-regulated expression of KA1 and endoplasmic reticulum stress occurred in the same nerve cells. Kainic acid first up-regulated the excitatory receptor KA1 expression, which may cause cell endoplasmic reticulum dysfunction and result in the endoplasmic reticulum stress response, further promoting neuronal cell death.



中国组织工程研究
杂志出版内容重点:肾移植肝移植移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植组织工程


全文链接:

Key words: kainic acid, endoplasmic reticulum, hippocampus

CLC Number: