Modulating microglia activation prevents maternal immune activation induced schizophrenia-relevant behavior phenotypes via arginase 1 in the dentate gyrus
- 29 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Neuropsychopharmacology
- Vol. 45 (11), 1896-1908
- https://doi.org/10.1038/s41386-020-0743-7
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.This publication has 88 references indexed in Scilit:
- Reversal of Behavioral Deficits and Synaptic Dysfunction in Mice Overexpressing Neuregulin 1Neuron, 2013
- Minocycline selectively inhibits M1 polarization of microgliaCell Death & Disease, 2013
- Detection of an immature dentate gyrus feature in human schizophrenia/bipolar patientsTranslational Psychiatry, 2012
- Effects of adult‐generated granule cells on coordinated network activity in the dentate gyrusHippocampus, 2010
- Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8Schizophrenia Research, 2010
- Maternal immune activation alters nonspatial information processing in the hippocampus of the adult offspringBrain, Behavior, and Immunity, 2010
- Adult-Born Hippocampal Dentate Granule Cells Undergoing Maturation Modulate Learning and Memory in the BrainJournal of Neuroscience, 2009
- Nitrosative stress and inducible nitric oxide synthase expression in periventricular leukomalaciaActa Neuropathologica, 2009
- The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies)Progress in Brain Research, 2007
- Pattern Separation in the Dentate Gyrus and CA3 of the HippocampusScience, 2007