論文

査読有り
2017年9月

Epidermal growth factor singals attenuate phenotypic and functional development of neocortical GABA neurons

JOURNAL OF NEUROCHEMISTRY
  • Hisaaki Namba
  • ,
  • Tadasato Nagano
  • ,
  • Eiichi Jodo
  • ,
  • Satoshi Eifuku
  • ,
  • Masao Horie
  • ,
  • Hirohide Takebayashi
  • ,
  • Yuriko Iwakura
  • ,
  • Hidekazu Sotoyama
  • ,
  • Nobuyuki Takei
  • ,
  • Hiroyuki Nawa

142
6
開始ページ
886
終了ページ
900
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/jnc.14097
出版者・発行元
WILEY

Phenotypic development of neocortical GABA neurons is highly plastic and promoted by various neurotrophic factors such as neuregulin-1. A subpopulation of GABA neurons expresses not only neuregulin receptor (ErbB4) but also epidermal growth factor (EGF) receptor (ErbB1) during development, but the neurobiological action of EGF on this cell population is less understood than that of neuregulin-1. Here, we examined the effects of exogenous EGF on immature GABA neurons both in culture and in vivo and also explored physiological consequences in adults. We prepared low density cultures from the neocortex of rat embryos and treated neocortical neurons with EGF. EGF decreased protein levels of glutamic acid decar-boxylases (GAD65 and GAD67), and EGF influences on neuronal survival and glial proliferation were negligible or limited. The EGF treatment also diminished the frequency of miniature inhibitory postsynaptic currents (mIPSCs). In vivo administration of EGF to mouse pups reproduced the above GABAergic phenomena in neocortical culture. In EGF-injected postnatal mice, GAD- and parvalbumin-immunoreactivities were reduced in the frontal cortex. In addition, postnatal EGF treatment decreased mIPSC frequency in, and the density of, GABAergic terminals on pyramidal cells. Although these phenotypic influences on GABA neurons became less marked during development, it later resulted in the reduced beta- and gamma-powers of sound-evoked electroencephalogram in adults, which is regulated by parvalbumin-positive GABA neurons and implicated in the schizophrenia pathophysiology. These findings suggest that, in contrast to the ErbB4 ligand of neuregulin-1, the ErbB1 ligand of EGF exerts unique maturation-attenuating influences on developing cortical GABAergic neurons.

Web of Science ® 被引用回数 : 6

リンク情報
DOI
https://doi.org/10.1111/jnc.14097
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000410431800008&DestApp=WOS_CPL