Maternal immune activation (MIA) during pregnancy, e.g. by environmental factors such as infection or toxins, is associated with an increased risk of neurodevelopmental disorders in the offspring of humans and in animal models, including autism spectrum disorder (ASD) and schizophrenia. Environmental factors such as air pollution have been less explored. We developed a novel mouse model in which pregnant mouse dams are exposed intermittently throughout pregnancy to diesel exhaust particles (DEP), a proxy for air pollution, vs. a control solution. Half of the dams in each group were further exposed to stress during the last third of pregnancy, using a restricted nest material paradigm. Both of these environmental exposures robustly activate the maternal immune system and are associated during pregnancy with increased ASD risk in humans. DEP exposure alone altered the development of the immune cells of the brain, called microglia, in the cortex of juvenile males, but not females; however no changes in behavior were observed in either sex. In contrast, offspring exposed prenatally to combined DEP + maternal stress (MS) showed striking, persistent deficits in communication, sociability, and cognition, but again only in males. Combined prenatal exposures altered synapse number in brain regions important for social behavior and communication, and we observed a striking shift in the phenotype, or “molecular makeup” of microglia within the same regions. These data suggest combined environmental exposures which activate the maternal immune system may persistently impact brain and behavioral development in males via impacts on immune cell developmental functions within the brain.
Part of the 2018-2019 Distinguished Lecturer Series at the UC Davis MIND Institute
