Microglia-derived neuregulin expression in psychiatric disorders

Daisuke Ikawa, Manabu Makinodan, Keiko Iwata, Masahiro Ohgidani, Takahiro A. Kato, Yasunori Yamashita, Kazuhiko Yamamuro, Sohei Kimoto, Michihiro Toritsuka, Takahira Yamauchi, Shin ichi Fukami, Hiroki Yoshino, Kazuki Okumura, Tatsuhide Tanaka, Akio Wanaka, Yuji Owada, Masatsugu Tsujii, Toshiro Sugiyama, Kenji Tsuchiya, Norio MoriRyota Hashimoto, Hideo Matsuzaki, Shigenobu Kanba, Toshifumi Kishimoto

研究成果: Contribution to journalArticle査読

20 被引用数 (Scopus)

抄録

Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.

本文言語英語
ページ(範囲)375-385
ページ数11
ジャーナルBrain, Behavior, and Immunity
61
DOI
出版ステータス出版済み - 3 1 2017

All Science Journal Classification (ASJC) codes

  • 免疫学
  • 内分泌系および自律システム
  • 行動神経科学

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