PRENATAL AIR POLLUTION AND MATERNAL STRESS ALTER BRAIN DEVELOPMENT IN THE ANTERIOR CINGULATE CORTEX

All Authors:
Carina L. Block, Duke University, Durham, United States (Primary Presenter)
Oznur L Eroglu, Duke University, Durham, United States
Steve L Mague, Duke University, Durham, United States
Kafui Dzirasa, Duke University, Durham, United States
Cagla Eroglu, Duke University, Durham, United States
Staci Bilbo, Massachusetts General Hospital for Children/Harvard Medical School, Charleston, United States
Caroline Smith, Massachusetts General Hospital for Children, Charlestown, United States

Prenatal air pollution (diesel exhaust particles; DEP) combined with maternal stress (MS) during the last trimester of gestation activate the maternal immune system and act synergistically on offspring to promote long lasting changes in neuroimmune function and deficits in behavior in adulthood. Microglia are the primary immune cells in the CNS, they are important in immune host defense and are involved normal brain development. Previous research has demonstrated that microglia are abnormal in several neurodevelopmental disorders, and in rodent models, transgenic manipulation of microglia number or function results in brain dysfunction. However, it is unclear whether environmentally relevant MIA produces a similar phenotype. In this study, we aimed to determine whether prenatal DEP and MS (DEP+MS) alter social behaviors, microglia infiltration and cortical development in the anterior cingulate cortex in offspring. Pregnant mouse dams were intermittently exposed via oropharyngeal aspiration to DEP (50 μg x 6 doses) or vehicle (VEH) throughout gestation. This exposure was combined with standard housing for dams or nest material restriction (a model of MS) during the last third of gestation. Prenatal DEP+MS altered social communication behavior in developing offspring. At postnatal day 15, prenatal DEP+MS resulted in changes in synaptic connectivity, development of microglia and astrocyte distribution in cortical regions implicated in autism. Together, these results suggest that environmental risk factors can alter microglia development/function, resulting in changes in brain development commonly seen in autism. This model thus affords a unique opportunity to explore environmentally relevant cellular and molecular mechanisms that contribute to neurodevelopmental disorders.