Many epidemiological studies have indicated that prenatal immune stress, frequently elicited by maternal immune activation, underlies a major risk for neuropsychiatric disorders of neurodevelopmental origin, such as schizophrenia and autism spectrum disorders. Animal models have been utilized to understand the biological processes of how immune stress influences brain development and resultant behavioral changes. Through such studies, the impacts of orchestrated immune-inflammatory mechanisms led by interleukin-6 (IL-6) on several developing cells, such as neural progenitors, neurons, and microglia, have been deciphered. In addition to prenatal immune stress from adverse maternal environments, mechanisms regulated by intrinsic factors directly associated with the offspring also exist. This review also introduces human stem cell models for addressing this topic and refers to potential modifiers of prenatal immune stress that could influence the eventual behavioral outcomes. Altogether, a mechanistic understanding of the impact of prenatal immune stress on brain development provides a fundamental addition in translational and clinical neurology and psychiatry.
Keywords: autism spectrum disorder; inflammatory cytokine; maternal immune activation; prenatal immune stress; schizophrenia.