Modulating microglia activation prevents maternal immune activation induced schizophrenia-relevant behavior phenotypes via arginase 1 in the dentate gyrus

Yucen Xia, Zhiqing Zhang, Weipeng Lin, Jinglan Yan, Chuan’an Zhu, Dongmin Yin, Su He, Yang Su, Nenggui Xu, Robert William Caldwell, Lin Yao, Yongjun Chen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Prenatal infection during pregnancy increases the risk for developing neuropsychiatric disorders such as schizophrenia. This is linked to an inflammatory microglial phenotype in the offspring induced by maternal immune activation (MIA). Microglia are crucial for brain development and maintenance of neuronal niches, however, whether and how their activation is involved in the regulation of neurodevelopment remains unclear. Here, we used a MIA rodent model in which polyinosinic: polycytidylic acid (poly (I:C)) was injected into pregnant mice. We found fewer parvalbumin positive (PV+) cells and impaired GABAergic transmission in the dentate gyrus (DG), accompanied by schizophrenia-like behavior in the adult offspring. Minocycline, a potent inhibitor of microglia activation, successfully prevented the above-mentioned deficits in the offspring. Furthermore, by using microglia-specific arginase 1 (Arg1) ablation as well as overexpression in DG, we identified a critical role of Arg1 in microglia activation to protect against poly (I:C) imparted neuropathology and altered behavior in offspring. Taken together, our results highlight that Arg1-mediated alternative activation of microglia are potential therapeutic targets for psychiatric disorders induced by MIA.

Original languageEnglish (US)
Pages (from-to)1896-1908
Number of pages13
JournalNeuropsychopharmacology
Volume45
Issue number11
DOIs
StatePublished - Oct 1 2020

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Modulating microglia activation prevents maternal immune activation induced schizophrenia-relevant behavior phenotypes via arginase 1 in the dentate gyrus'. Together they form a unique fingerprint.

Cite this