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演題詳細

Poster

マウス大脳皮質ニューロンへの子宮内電気穿孔法によるTDP-43核内封入体-電子顕微鏡による観察
Electron microscopic observation of intranuclear aggregation of TDP-43 in mouse cerebral cortex produced by in utero electroporation

  • P1-315
  • 赤松 恵 / Megumi Akamatsu:1 詫間 浩 / Hiroshi Takuma:1 山下 雄也 / Takenari Yamashita:2 岡田 拓也 / Takuya Okada:3 桝 和子 / Kazuko Keino-Masu:3 Oehring Hartmut / Hartmut Oehring:4 郭 伸 / Shin Kwak:2 桝 正幸 / Masayuki Masu:3 Jirikowsk Gustav F / Gustav F Jirikowski:4 玉岡 晃 / Akira Tamaoka:1 
  • 1:筑波大・医・神経内科 / Dept Neurol, Univ of Tsukuba, Ibaraki, Japan 2:東京大院・医・疾患生命工学 / Dept Clinc Biotechnol, Univ of Tokyo, Tokyo, Japan 3:筑波大・医・分子神経生物 / Dept Mol Neurobiol, Univ of Tsukuba, Ibaraki, Japan 4:Dept Anatomy II, Friedrich-Schiller Univ Jena, Jena, Germany / Dept Anatomy II, Friedrich-Schiller Univ Jena, Jena, Germany  

RNA-binding protein TDP-43 is the discriminative protein that is found as intracellular aggregation in neurons of the cerebral cortex and spinal cord in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). In the aggregations, TDP-43 exists as phosphorylated, C-terminally cleaved and ubiquitinated. However, the mechanisms of neuronal loss and the relation to the aggregations are still unclear. We previously reported the intracellular and intranuclear aggregations were produced by exogenous TDP-43 by in utero electroporation, although the intranuclear aggregations existed much less frequently than intracellular in ALS. We observed here the intranuclear TDP-43 aggregations by electron microscope (EM). GFP tagged full length (FL) and C-terminally fragmented form (Ctf) TDP-43 were electroporated into mice embryo's motor cortex, and the brains were subjected to immunohistochemical and EM analysis. Some subcellular organelles such as mitochondria were included in the perinuclear aggregations by Ctf-TDP-43. Moreover we observed the intranuclear aggregations by Ctf-TDP-43, some of the intranuclear aggregations contacted with inner membrane of nucleus. It suggested that the intranuclear aggregations of TDP-43 included chromatin and then may influence on many functions in nucleus. Furthermore we observed the apoptotic neurons in the brains that were electroporated Ctf-TDP-43. We evaluated the number of apoptotic cells in mice embryo brains and they were significantly increased in Ctf-TDP-43 electroporated mice compared to the control and FL-TDP-43 electroporated mice. This suggested that the aggregations of TDP-43 have some toxicity for neurons.

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