論文

査読有り
2013年3月

Synaptosomal-associated protein 25 mutation induces immaturity of the dentate granule cells of adult mice

MOLECULAR BRAIN
  • Koji Ohira
  • ,
  • Katsunori Kobayashi
  • ,
  • Keiko Toyama
  • ,
  • Hironori K. Nakamura
  • ,
  • Hirotaka Shoji
  • ,
  • Keizo Takao
  • ,
  • Rika Takeuchi
  • ,
  • Shun Yamaguchi
  • ,
  • Masakazu Kataoka
  • ,
  • Shintaro Otsuka
  • ,
  • Masami Takahashi
  • ,
  • Tsuyoshi Miyakawa

6
12
開始ページ
1
終了ページ
17
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1186/1756-6606-6-12
出版者・発行元
BIOMED CENTRAL LTD

Background: Synaptosomal-associated protein, 25 kDa (SNAP-25) regulates the exocytosis of neurotransmitters. Growing evidence suggests that SNAP-25 is involved in neuropsychiatric disorders, such as schizophrenia, attention-deficit/hyperactivity disorder, and epilepsy. Recently, increases in anxiety-related behaviors and epilepsy have been observed in SNAP-25 knock-in (KI) mice, which have a single amino acid substitution of Ala for Ser187. However, the molecular and cellular mechanisms underlying the abnormalities in this mutant remain unknown.
Results: In this study, we found that a significant number of dentate gyrus (DG) granule cells was histologically and electrophysiologically similar to immature DG neurons in the dentate gyrus of the adult mutants, a phenomenon termed the "immature DG" (iDG). SNAP-25 KI mice and other mice possessing the iDG phenotype, i.e., alphacalcium/calmodulin-dependent protein kinase II heterozygous mice, Schnurri-2 knockout mice, and mice treated with the antidepressant fluoxetine, showed similar molecular expression patterns, with over 100 genes similarly altered. A working memory deficit was also identified in mutant mice during a spontaneous forced alternation task using a modified T-maze, a behavioral task known to be dependent on hippocampal function. Chronic treatments with the antiepileptic drug valproate abolished the iDG phenotype and the working memory deficit in mutants.
Conclusions: These findings suggest that the substitution of Ala for Ser187 in SNAP-25 induces the iDG phenotype, which can also be caused by epilepsy, and led to a severe working memory deficit. In addition, the iDG phenotype in adulthood is likely an endophenotype for at least a part of some common psychiatric disorders.

Web of Science ® 被引用回数 : 37

リンク情報
DOI
https://doi.org/10.1186/1756-6606-6-12
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000316320400001&DestApp=WOS_CPL
ID情報
  • DOI : 10.1186/1756-6606-6-12
  • ISSN : 1756-6606
  • Web of Science ID : WOS:000316320400001

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