Viral infections during pregnancy are associated with increased incidence of psychiatric disorders in offspring. The pathological outcomes of viral infection appear to be caused by the deleterious effects of innate immune response-associated factors on development of the fetus, which predispose the offspring to pathological conditions in adulthood. The negative impact of viral infections varies substantially between pregnancies. Here, we explored whether differential stress sensitivity underlies the high heterogeneity of immune reactivity and whether this may influence the pathological consequences of maternal immune activation. Using mouse models of social dominance (Dom) and submissiveness (Sub), which possess innate features of stress resilience and vulnerability, respectively, we identified differential immune reactivity to the synthetic analogue of viral double-stranded RNA, Poly(I:C), in Sub and Dom nulliparous and pregnant females. More specifically, we found that Sub females showed an exacerbated pro- and anti-inflammatory cytokine response to Poly(I:C) as compared with Dom females. Sub offspring born to Sub mothers (stress sensitive offspring) showed enhanced locomotory response to the non-competitive NMDA antagonist, MK-801, which was potentiated by prenatal Poly(I:C) exposure. Our findings suggest that inherited stress sensitivity may lead to functional changes in glutamatergic signaling, which in turn is further exacerbated by prenatal exposure to viral-like infection. The maternal immunome seems to play a crucial role in these observed phenomena.
Keywords: Cytokine storm; MK-801; Maternal immune activation; Poly(I:C); Social rank; Stress sensitivity.
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