Maternal immune activation, central nervous system development and behavioral phenotypes

Abstract

Maternal immune activation (MIA) refers to a maternal immune system triggered by infectious or infectious-like stimuli. A cascade of cytokines and immunologic alterations are transmitted to the fetus, resulting in adverse phenotypes most notably in the central nervous system. Epidemiologic studies implicate maternal infections in a variety of neuropsychiatric disorders, most commonly autism spectrum disorders and schizophrenia. In animal models, MIA causes neurochemical and anatomic changes in the brain that correspond to those found in humans with the disorders. As our understanding of the interactions between environment, genetics, and immune system grows, the role of alternative, noninfectious risk factors, such as prenatal stress, obesity, and the gut microbiome also becomes clearer. This review considers how infectious and noninfectious etiologies activate the maternal immune system. Their impact on fetal programming and neuropsychiatric disorders in offspring is examined in the context of human and animal studies.

Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

“…Based on findings from the cytokine studies mentioned above, various mechanisms to explain how MIA leads to long-term behavioural abnormalities in ASD have been proposed [107]. In particular, the dysregulated production of IL-6 has been consistently implicated as a downstream effect of MIA [108].…”

Immuno-psychiatrie et pandémie de SARS-CoV-2 : liens et possibles conséquences

“…Cette hypothèse d’activation immunitaire maternelle ( MIA, maternal immun activation ) a été testée dans des modèles animaux, « le modèle immun maternel » basé sur l’activation du système immunitaire pendant la grossesse par différents agents stressants puis en observant les modifications neuro-développementales et comportementales chez les descendants. Le modèle immun maternel consiste en effet à injecter à un animal gestant, soit directement d’un agent pathogène (virus, bactérie), soit un dérivé tel que l’acide polyinosinique-polycytidylique (poly [I :C]), mimant une infection virale, ou un lipopolysaccharide (LPS) (composant essentiel de la paroi bactérienne des bactéries à Gram négatif), mimant une infection bactérienne, soit des interleukines pro-inflammatoires (Il-1, IL-6, IL-17) [34] .…”

What Does Immunology Have to Do With Normal Brain Development and the Pathophysiology Underlying Tourette Syndrome and Related Neuropsychiatric Disorders?

“…The effect of stressors in pregnancy also remains underexplored in these conditions. There is, nevertheless, well-established evidence that stressors cause overproduction of proinflammatory cytokines by immune cells in response to immunostimulants, and alterations in the HPA axis, which may also influence the development of immune responses in the offspring, especially T and B cell proliferation, NK cell cytotoxicity, and cytokine receptor density (239,240).…”

“…MIA models based on Poly I:C demonstrated the activity of maternal immune cells in the placenta, particularly in association with increased IL-6 production at the maternal-fetal interface. The placenta might also modulate stress responses induced by prenatal stress-induced MIA, mediating the metabolism of glucocorticoids into inactive metabolites ( 240 ).…”