Chinese Journal of Tissue Engineering Research ›› 2015, Vol. 19 ›› Issue (51): 8259-8265.doi: 10.3969/j.issn.2095-4344.2015.51.011

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Tunicamycin-induced neuronal death in the hippocampus: new phenomenon and new hypothesis

Yuan Lei1, 2, Deng Si-min3, Zhang Hai-xia1, Qian Shi-lei1, Xu Bin1, Gong Ji-qin1, Zeng Jie1, Pan Juan4,
Liu Hong-zhe2, Hu Ming-hua1, Wu Chang-chu1   

  1. 1Hunan Provincial Key Laboratory of Human Anatomy and Histoembryology, Key Disciplines in Hunan Province, Changsha Medical University, Changsha 410219, Hunan Province, China; 2Department of Spine Surgery, Hunan Provincial People’s Hospital, Changsha 410005, Hunan Province, China; 3the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China; 4Department of Cardiology, Hunan Provincial People’s Hospital, Changsha 410005, Hunan Province, China
  • Received:2015-10-24 Online:2015-12-10 Published:2015-12-10
  • Contact: Wu Chang-chu, Associate professor, Hunan Provincial Key Laboratory of Human Anatomy and Histoembryology, Key Disciplines in Hunan Province, Changsha Medical University, Changsha 410219, Hunan Province, China
  • About author:Yuan Lei, Physician, Hunan Provincial Key Laboratory of Human Anatomy and Histoembryology, Key Disciplines in Hunan Province, Changsha Medical University, Changsha 410219, Hunan Province, China; Department of Spine Surgery, Hunan Provincial People's Hospital, Changsha 410005, Hunan Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81171136; Research Learning and Innovative Experiment Project of Undergraduates in Hunan Province, No. [2013]191-431, [2012]402-445; the Scientific Research Project of Higher Education in Hunan Province, No. 10A013; the Key Discipline Construction Project in Higher Education of Hunan Province during the Twelfth Five-Year Period, No. [2011]76

Abstract:

BACKGROUND: Although both tunicamycin and kainic acid can induce neuronal apoptosis in the hippocampus, their processes are very different.
OBJECTIVE: To compare the death of hippocampal neurons induced by injection of tunicamycin and kainic acid into the hippocampal CA1 region.
METHODS: Ninety-six adult male Kunming mice were randomized into PBS, tunicamycin and kainic acid groups, and then subjected to microinjections of PBS, tunicamycin and kainic acid into the hippocampus, respectively.
 
RESULTS AND CONCLUSION: Fluoro-Jade B staining showed that at 2, 3, 4, 5, 6 and 8 hours after kainic acid injection, hippocampal neurons appeared to have obvious death at the injured CA1 region; at 4 hours after tunicamycin injection, neuronal death was visible at the injured CA region rather than at the contralateral CA1 region; at 5 hours after tunicamycin injection, there were a large of dead neurons in the contralateral CA1 region rather than at the injured CA1 region. Immunohistochemical staining showed that the expression of phosphorylated eukaryotic initiation factor 2α at the apoptotic region was up-regulated significantly at 4 and 5 hours after tunicamycin injection. These findings indicate that with the diffusion of tunicamycin concentration, the neuronal apoptosis may have a trend to spread rapidly from the ipsilateral to the contralateral CA1 region at 4-5 hours after hippocampal injection of tunicamycin, and this process is a new discovery that is different from kainic acid-induced hippocampal neuron apoptosis. 

 

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