論文

査読有り
2016年3月

Reciprocal Alterations in Regulator of G Protein Signaling 4 and microRNA16 in Schizophrenia

SCHIZOPHRENIA BULLETIN
  • Sohei Kimoto
  • ,
  • Jill R. Glausier
  • ,
  • Kenneth N. Fish
  • ,
  • David W. Volk
  • ,
  • H. Holly Bazmi
  • ,
  • Dominique Arion
  • ,
  • Dibyadeep Datta
  • ,
  • David A. Lewis

42
2
開始ページ
396
終了ページ
405
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/schbul/sbv139
出版者・発行元
OXFORD UNIV PRESS

N-methyl-D-aspartate receptor (NMDAR) hypofunction in the dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathology of schizophrenia. NMDAR activity is negatively regulated by some G protein-coupled receptors (GPCRs). Signaling through these GPCRs is reduced by Regulator of G protein Signaling 4 (RGS4). Thus, lower levels of RGS4 would enhance GPCR-mediated reductions in NMDAR activity and could contribute to NMDAR hypofunction in schizophrenia. In this study, we quantified RGS4 mRNA and protein levels at several levels of resolution in the DLPFC from subjects with schizophrenia and matched healthy comparison subjects. To investigate molecular mechanisms that could contribute to altered RGS4 levels, we quantified levels of small noncoding RNAs, known as microRNAs (miRs), which regulate RGS4 mRNA integrity after transcription. RGS4 mRNA and protein levels were significantly lower in schizophrenia subjects and were positively correlated across all subjects. The RGS4 mRNA deficit was present in pyramidal neurons of DLPFC layers 3 and 5 of the schizophrenia subjects. In contrast, levels of miR16 were significantly higher in the DLPFC of schizophrenia subjects, and higher miR16 levels predicted lower RGS4 mRNA levels. These findings provide convergent evidence of lower RGS4 mRNA and protein levels in schizophrenia that may result from increased expression of miR16. Given the role of RGS4 in regulating GPCRs, and consequently the strength of NMDAR signaling, these findings could contribute to the molecular substrate for NMDAR hypofunction in DLPFC pyramidal cells in schizophrenia.

Web of Science ® 被引用回数 : 10

リンク情報
DOI
https://doi.org/10.1093/schbul/sbv139
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26424323
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000376401500018&DestApp=WOS_CPL