論文

査読有り
2016年7月

Cortical Gene Expression After a Conditional Knockout of 67 kDa Glutamic Acid Decarboxylase in Parvalbumin Neurons

SCHIZOPHRENIA BULLETIN
  • Danko Georgiev
  • ,
  • Toru Yoshihara
  • ,
  • Rika Kawabata
  • ,
  • Takurou Matsubara
  • ,
  • Makoto Tsubomoto
  • ,
  • Yoshio Minabe
  • ,
  • David A. Lewis
  • ,
  • Takanori Hashimoto

42
4
開始ページ
992
終了ページ
1002
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/schbul/sbw022
出版者・発行元
OXFORD UNIV PRESS

In the cortex of subjects with schizophrenia, expression of glutamic acid decarboxylase 67 (GAD67), the enzyme primarily responsible for cortical GABA synthesis, is reduced in the subset of GABA neurons that express parvalbumin (PV). This GAD67 deficit is accompanied by lower cortical levels of other GABA-associated transcripts, including GABA transporter-1, PV, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B, somatostatin, GABA A receptor a1 subunit, and KCNS3 potassium channel subunit mRNAs. In contrast, messenger RNA (mRNA) levels for glutamic acid decarboxylase 65 (GAD65), another enzyme for GABA synthesis, are not altered. We tested the hypothesis that this pattern of GABA-associated transcript levels is secondary to the GAD67 deficit in PV neurons by analyzing cortical levels of these GABA-associated mRNAs in mice with a PV neuron-specific GAD67 knockout. Using in situ hybridization, we found that none of the examined GABA-associated transcripts had lower cortical expression in the knockout mice. In contrast, PV, BDNF, KCNS3, and GAD65 mRNA levels were higher in the homozygous mice. In addition, our behavioral test battery failed to detect a change in sensorimotor gating or working memory, although the homozygous mice exhibited increased spontaneous activities. These findings suggest that reduced GAD67 expression in PV neurons is not an upstream cause of the lower levels of GABA-associated transcripts, or of the characteristic behaviors, in schizophrenia. In PV neuron- specific GAD67 knockout mice, increased levels of PV, BDNF, and KCNS3 mRNAs might be the consequence of increased neuronal activity secondary to lower GABA synthesis, whereas increased GAD65 mRNA might represent a compensatory response to increase GABA synthesis.

Web of Science ® 被引用回数 : 14

リンク情報
DOI
https://doi.org/10.1093/schbul/sbw022
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26980143
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000385280800021&DestApp=WOS_CPL
ID情報
  • DOI : 10.1093/schbul/sbw022
  • ISSN : 0586-7614
  • eISSN : 1745-1701
  • PubMed ID : 26980143
  • Web of Science ID : WOS:000385280800021

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