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Glia and Glia-Neuron Interaction

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Ablation of NG2 glial cells induced apoptosis in hippocampal neurons through TNFα pathway

  • P2-065
  • 中野 真行 / Masayuki Nakano:1,2 田村 泰久 / Yasuhisa Tamura:1 江口 麻美 / Asami Eguchi:1 大和 正典 / Masanori Yamato:1 久米 慧嗣 / Satoshi Kume:1 宮繁 志治 / Yukiharu Miyashige:1 片岡 洋祐 / Yosky Kataoka:1,2 
  • 1:理研ライフサイエンス技術基盤研セ細胞機能評価 / Cellular Function Imaging, Riken CLST, Kobe, Japan 2:大阪市大院医システム神経 / Dept of Physiol, Grad Sch of Med, Osaka City Univ, Osaka, Japan 

Glial progenitor cells expressing chondroitin sulfate proteoglycan 4 (NG2), are termed as NG2 glial cells (or oligodendrocyte precursor cells), and comprise the majority of proliferative cells in the adult central nervous system (CNS). Recently, it was reported that NG2 glial cells rapidly migrate and proliferate to restore their density in response to focal loss of the cells, such as acute CNS injury, ischemia, and demyelination. Moreover, NG2 glial cells are known to receive direct synaptic inputs from neurons, and are often located adjacent to neuronal somata, suggesting any interactions between NG2 glial cells and neurons, although substantive roles of the NG2 glial cells without cell reproduction have not been elucidated.
In order to investigate the roles of NG2 glial cells, we produced transgenic rats expressing herpes simplex virus thymidine kinase (HSV-TK) under control of the promoter for NG2. In the brain of transgenic rats, almost all NG2 glial cells expressed HSV-TK. We tried to selectively ablate proliferating NG2 glial cells by continuous administration of anti-viral agents into the lateral ventricle, and succeeded in rapid degeneration of the NG2 glial cells in the tissue around the lateral ventricle including the hippocampus. In the brain, surprisingly, the number of hippocampal neurons was dramatically decreased depending on the reduction of NG2 glial cells. To investigate the mechanism of neuronal cell death, we applied microarray analyses to the hippocampal tissue following ablation of NG2 glial cells. The expression profile revealed that ablation of NG2 glial cells increased the expression of tumor necrosis factor alpha (TNFα). Immunohistochemical staining demonstrated that the hippocampal neurons contained TNF receptor type 1 (TNFR1) involved in a signaling pathway for apoptosis. Furthermore, TUNEL staining actually revealed that hippocampal neurons underwent apoptosis following the NG2 glial cell ablation. These results suggested that NG2 glial cells maintain neuronal function and survival by regulating the anti-inflammatory pathway under the physiological condition.

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