MISC

2008年5月

Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA-mediated down-regulation of the glucocorticoid receptor

EUROPEAN JOURNAL OF NEUROSCIENCE
  • Shusaku Uchida
  • ,
  • Akira Nishida
  • ,
  • Kumiko Hara
  • ,
  • Toshiki Kamemoto
  • ,
  • Masatomo Suetsugi
  • ,
  • Michiko Fujimoto
  • ,
  • Toshio Watanuki
  • ,
  • Yusuke Wakabayashi
  • ,
  • Koji Otsuki
  • ,
  • Bruce S. McEwen
  • ,
  • Yoshifumi Watanabe

27
9
開始ページ
2250
終了ページ
2261
記述言語
英語
掲載種別
DOI
10.1111/j.1460-9568.2008.06218.x
出版者・発行元
BLACKWELL PUBLISHING

In the present study, we established and characterized an animal model of vulnerability to repeated stress. We found that control Sprague-Dawley (SD) rats showed a gradual decrease in the HPA axis response following 14 days of repeated restraint stress, whereas Fischer 344 (F344) rats did not show such HPA axis habituation. Similar habituation was observed in the expression of c-fos mRNA, corticotropin-releasing hormone hnRNA, and phospho-CREB and phospho-ERK proteins in the hypothalamic paraventricular nucleus (PVN) of SD rats, but not in the F344 rats. In addition, repeatedly restrained F344 rats exhibited decreased cell proliferation in the dentate gyrus of the hippocampus and increased anxiety-related behaviours, while repeatedly restrained SD rats exhibited a selective enhancement of hippocampal cell proliferation in the ventral area. Moreover, we found a lower expression of glucocorticoid receptor (GR) protein, but not mRNA, in the PVN of F344 rats compared to SD rats. We also identified that microRNA (miR)-18a inhibited translation of GR mRNA in cultured neuronal cells and that increased expression of miR-18a in the PVN was observed in F344 rats compared with SD rats. These strain differences in GR protein levels were not found in the hippocampus and prefrontal cortex, and the expression of miR-18a was much lower in these brain regions than in the PVN. Our results suggest that F344 rats could be a useful animal model for studying vulnerability to repeated stress, and that miR-18a-mediated down-regulation of GR translation may be an important factor to be considered in susceptibility to stress-related disorders.

Web of Science ® 被引用回数 : 148

リンク情報
DOI
https://doi.org/10.1111/j.1460-9568.2008.06218.x
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000255285800005&DestApp=WOS_CPL

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