The prenatal environment, and in particular, the maternal-fetal immune environment, has emerged as a targeted area of research for central nervous system (CNS) diseases with neurodevelopmental origins. The ability to accurately predict risk and resilience would provide evidence-based guidelines for women’s health and opportunities to identify children at risk for neurodevelopmental disorders who would benefit from early interventions that have been associated with better outcomes. The overarching goal of the Bauman Laboratory is to make meaningful contributions that accelerate translation from basic science to improve human health.
Maternal Immune Activation (MIA)
Women exposed to infection during pregnancy have an increased likelihood of giving birth to a child who will be diagnosed with a neurodevelopmental or neuropsychiatric condition. Decades of converging evidence from epidemiological and preclinical research suggests that the maternal immune response is the critical link between exposure to a variety of viral and bacterial infections during pregnancy and alterations in fetal brain development. Although most women report experiencing at least one infection during pregnancy, it is also important to note that the vast majority of children exposed to prenatal immune challenges will not experience significant neurodevelopmental changes. There is a critical need to understand factors that determine risk and resilience to changes in the maternal-placental-fetal immune environment and to develop evidence-based guidelines for managing infection during pregnancy. Many laboratories use preclinical rodent maternal immune activation (MIA) models to explore the mechanisms linking elevated maternal cytokines with aberrant offspring neurodevelopment. Over the past 15 years, the Bauman Laboratory has led efforts to establish a novel nonhuman primate MIA model. We have shown that nonhuman primates born to MIA-treated dams exhibit lasting changes in brain and behavioral development, alterations in species-typical social and cognitive behavior, reduced cortical volumes, neuroinflammation, aberrant dopamine function, and altered brain metabolites. New studies carried out in collaboration with Dr. Cyndi Schumann and Dr. Erin Kinnally are underway to provide mechanistic insight into the cellular/molecular neurobiological consequences of prenatal immune challenge.
Maternal Autoantibodies Related (MAR) Autism
Maternal autoantibodies targeting fetal brain proteins are strongly associated with an increased likelihood of autism diagnosis. In collaboration with Dr. Judy Van de Water, the Bauman Laboratory has utilized a combination of rodent and nonhuman primate models to explore the pathogenicity of these autoantibodies in preclinical animal models. Building upon previous passive transfer models, we have recently established a translationally relevant antigen-driven model whereby autoantibody production is induced in rat dams through injection with autism- specific autoantigen peptides. Antibodies can then transfer to offspring and influence developmental outcomes. Gestational exposure to MAR antibodies results in longitudinal, sex-specific effects on offspring outcomes including behavior, brain structure, and neurometabolism reminiscent of findings observed in clinical ASD. This paper includes immunohistochemistry, longitudinal behavioral phenotyping, and both magnetic resonance imaging and spectroscopy.
Prenatal Exposure to THC
Cannabis use during pregnancy is relatively common and increasing as more states legalize medical and recreational use. Δ9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis, readily crosses both the placenta and blood brain barrier, and may alter fetal brain development by binding to the endogenous cannabinoid family of receptors. In collaboration with Dr. Karen Bales, the Bauman Laboratory has initiated pilot experiments to develop translationally relevant animal models of prenatal THC exposure.