Astroglial major histocompatibility complex class I following immune activation leads to behavioral and neuropathological changes

Akira Sobue, Norimichi Ito, Taku Nagai, Wei Shan, Kazuhiro Hada, Akira Nakajima, Yuki Murakami, Akihiro Mouri, Yasuko Yamamoto, Toshitaka Nabeshima, Kuniaki Saito, Kiyofumi Yamada

研究成果: Article査読

22 被引用数 (Scopus)

抄録

In the central nervous system, major histocompatibility complex class I (MHCI) molecules are mainly expressed in neurons, and neuronal MHCI have roles in synapse elimination and plasticity. However, the pathophysiological significance of astroglial MHCI remains unclear. We herein demonstrate that MHCI expression is up-regulated in astrocytes in the medial prefrontal cortex (mPFC) following systemic immune activation by an intraperitoneal injection of polyinosinic-polycytidylic acid (polyI:C) or hydrodynamic interferon (IFN)-γ gene delivery in male C57/BL6J mice. In cultured astrocytes, MHCI/H-2D largely co-localized with exosomes. To investigate the role of astroglial MHCI, H-2D, or sH-2D was expressed in the mPFC of male C57/BL6J mice using an adeno-associated virus vector under the control of a glial fibrillary acidic protein promoter. The expression of astroglial MHCI in the mPFC impaired sociability and recognition memory in mice. Regarding neuropathological changes, MHCI expression in astrocytes significantly activated microglial cells, decreased parvalbumin-positive cell numbers, and reduced dendritic spine density in the mPFC. A treatment with GW4869 that impairs exosome synthesis ameliorated these behavioral and neuropathological changes. These results suggest that the overexpression of MHCI in astrocytes affects microglial proliferation as well as neuronal numbers and spine densities, thereby leading to social and cognitive deficits in mice, possibly via exosomes created by astrocytes.

本文言語English
ページ(範囲)1034-1052
ページ数19
ジャーナルGLIA
66
5
DOI
出版ステータスPublished - 05-2018

All Science Journal Classification (ASJC) codes

  • 神経学
  • 細胞および分子神経科学

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