論文

2017年10月

Dendritic Homeostasis Disruption in a Novel Frontotemporal Dementia Mouse Model Expressing Cytoplasmic Fused in Sarcoma

EBIOMEDICINE
  • Gen Shiihashi
  • ,
  • Daisuke Ito
  • ,
  • Itaru Arai
  • ,
  • Yuki Kobayashi
  • ,
  • Kanehiro Hayashi
  • ,
  • Shintaro Otsuka
  • ,
  • Kazunori Nakajima
  • ,
  • Michisuke Yuzaki
  • ,
  • Shigeyoshi Itohara
  • ,
  • Norihiro Suzuki

24
開始ページ
102
終了ページ
115
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ebiom.2017.09.005
出版者・発行元
ELSEVIER SCIENCE BV

Cytoplasmic aggregation of fused in sarcoma (FUS) is detected in brain regions affected by amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which compose the disease spectrum, FUS proteinopathy. To understand the pathomechanism of ALS-FTD-associated FUS, we examined the behavior and cellular properties of an ALS mouse model overexpressing FUS with nuclear localization signal deletion. Mutant FUS transgenic mice showed hyperactivity, social interactional deficits, and impaired fear memory retrieval, all of which are compatible with FTD phenotypes. Histological analyses showed decreased dendritic spine and synaptic density in the frontal cortex before neuronal loss. Examination of cultured cells confirmed that mutant but not wildtype FUS was associated with decreased dendritic growth, mRNA levels, and protein synthesis in dendrites. These data suggest that cytoplasmic FUS aggregates impair dendritic mRNA trafficking and translation, in turn leading to dendritic homeostasis disruption and the development of FTD phenotypes. (C) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license

Web of Science ® 被引用回数 : 8

リンク情報
DOI
https://doi.org/10.1016/j.ebiom.2017.09.005
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000414392900023&DestApp=WOS_CPL

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