Prenatal environmental stressors impair postnatal microglia function and social behavior in male mice. (September 2021)

• Record Type: Journal Article
• Authors: Block, C.L.; Smith, C.J.; Mague, S.D.; Dzirasa, K.; Eroglu, C.; Bilbo, S.D.
• Is Part Of: Psychoneuroendocrinology. Volume 131(2021)Supplement
• Publication Date: 2021-09
• Subjects: Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2021.105540
• Languages: English
• ISSNs: 0306-4530

Abstract

Abstract : Background: 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. Despite the critical role for microglia in neural development, few studies have examined the impact of MIA on microglial development or long-term function. Methods: We modeled these prenatal risk factors in mice, by co-exposing pregnant dams to an environmental pollutant and limited-resource stress, which robustly activated and dysregulated the maternal immune system. Results: Only male offspring displayed long-lasting behavioral abnormalities and alterations in the activity of brain networks encoding social interactions. Cellularly, prenatal stressors diminished microglial synaptic pruning functions within the anterior cingulate cortex (ACC), a central node of the social coding network, in males during early postnatal development. Finally, precise inhibition of microglial pruning within the ACC during the same critical period mimicked the impact of prenatal stressors on male social behavior. Conclusions: These data suggest combined environmental exposures which dysregulate the maternal immune system may persistently impact brain and behavioral development in males via impacts on microglial phagocytic and inflammatory function.