The Time of Prenatal Immune Challenge Determines the Specificity of Inflammation-Mediated Brain and Behavioral Pathology

TLDR

Prenatal maternal infection increases the risk of neuropsychiatric disorders such as autism and schizophrenia by triggering cytokine‑mediated neurodevelopmental defects during early brain development. The study aims to determine whether fetal brain cytokine expression following maternal immune challenge predicts the specific brain and behavioral pathology that emerges later. Maternal immune challenge during middle versus late gestation produces distinct fetal brain cytokine responses and leads to different vulnerabilities to adult behavioral dysfunction, adolescent brain neuropathology, and fetal cytokine profiles.

Abstract

Disturbance to early brain development is implicated in several neuropsychiatric disorders including autism, schizophrenia, and mental retardation. Epidemiological studies have indicated that the risk of developing these disorders is enhanced by prenatal maternal infection, presumably as a result of neurodevelopmental defects triggered by cytokine-related inflammatory events. Here, we demonstrate that the effects of maternal immune challenge between middle and late gestation periods in mice are dissociable in terms of fetal brain cytokine responses to maternal inflammation and the pathological consequences in brain and behavior. Specifically, the relative expression of pro- and anti-inflammatory cytokines in the fetal brains in response to maternal immune challenge may be an important determinant among other developmental factors for the precise pathological profile emerging in later life. Thus, the middle and late gestation periods correspond to two windows with differing vulnerability to adult behavioral dysfunction, brain neuropathology in early adolescence, and of the acute cytokine responses in the fetal brain.