Maternal Immune Activation Induces Sustained Changes in Fetal Microglia Motility

Kana Ozaki,Daisuke Kato,Ako Ikegami,Akari Hashimoto,Shouta Sugio,Zhongtian Guo, Midori Shibushita,Tsuyako Tatematsu,Koichiro Haruwaka,Andrew J. Moorhouse,Hideto Yamada,Hiroaki Wake

Scientific reports（2020）SCI 3区

Division of System Neuroscience | Department of Anatomy and Molecular Cell Biology | School of Medical Sciences | Department of Obstetrics and Gynecology

Cited 57|Views29

Abstract

Maternal infection or inflammation causes abnormalities in brain development associated with subsequent cognitive impairment and in an increased susceptibility to schizophrenia and autism spectrum disorders. Maternal immune activation (MIA) and increases in serum cytokine levels mediates this association via effects on the fetal brain, and microglia can respond to maternal immune status, but consensus on how microglia may respond is lacking and no-one has yet examined if microglial process motility is impaired. In this study we investigated how MIA induced at two different gestational ages affected microglial properties at different developmental stages. Immune activation in mid-pregnancy increased IL-6 expression in embryonic microglia, but failed to cause any marked changes in morphology either at E18 or postnatally. In contrast MIA, particularly when induced earlier (at E12), caused sustained alterations in the patterns of microglial process motility and behavioral deficits. Our research has identified an important microglial property that is altered by MIA and which may contribute to the underlying pathophysiological mechanisms linking maternal immune status to subsequent risks for cognitive disease.

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Key words

Autism spectrum disorders,Development of the nervous system,Diseases of the nervous system,Glial development,Neuroscience,Science,Humanities and Social Sciences,multidisciplinary

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