Centre for Biological Signalling Studies

Maternal Type-I interferon signaling adversely affects the microglia and the behavior of the offspring accompanied by increased sensitivity to stress.

Ben-Yehuda H, Matcovitch-Natan O, Kertser A, Spinrad A, Prinz M, Amit I, Schwartz M.

Mol Psychiatry. 2019 Nov 26. [Epub ahead of print]

Mol Psychiatry.              online article

Viral infection during pregnancy is often associated with neuropsychiatric conditions. In mice, exposure of pregnant dams to the viral mimetic poly(I:C), serves as a model that simulates such pathology in the offspring, through a process known as Maternal Immune Activation (MIA). To investigate the mechanism of such effect, we hypothesized that maternal upregulation of Type-I interferon (IFN-I), as part of the dam's antiviral response, might contribute to the damage imposed on the offspring. Using mRNA sequencing and flow cytometry analyses we found that poly(I:C) treatment during pregnancy caused reduced expression of genes related to proliferation and cell cycle in the offspring's microglia relative to controls. In addition, by adopting a "two-hit" experimental paradigm, we show a higher sensitivity of the offspring to postnatal stress subsequent to the maternal IFNβ elevation, demonstrated by behavioral irregularities. Our results suggest that maternal upregulation of IFN-I, in response to MIA, interferes with the offspring's programmed microglial developmental cascade, increases their susceptibility to postnatal stress, and leads to behavioral abnormalities.