Roles of gender and prenatal inflammation in autism
How do immune cells support healthy brain development and function?
Microglial cells are resident immune cells in the brain that function as guards for infection and injury. However, deregulation of microglia-mediated immune responses is known to be involved in many diseases, including autism spectrum disorders. Autism is characterized by difficulties in social communication and learning and is often associated with repetitive behaviors. Accumulated evidence suggests that inflammation in the developing brain plays a role in the development of autism. Thus, our research is focused on using a prenatal inflammation-induced mouse model of autism to elucidate the molecular mechanisms behind how defective microglial immune responses affect normal brain development, resulting in disease.
How can we develop a new therapeutic strategy for autism using nuclear hormone receptors?
Previous work in the lab has been focused on understanding the molecular mechanisms of how nuclear hormone receptors regulate immune responses in microglia. We are particularly interested in sex hormone nuclear receptors, including estrogen receptors (ERα and ERβ&341; and androgen receptor (AR), because autism affects many more boys than girls. Recently, we found that a subset of sex hormones produced by microglia bind to ERβ and repress the inflammatory response. Therefore, we will test the hypothesis that these sex hormones can repress inflammation and restore normal immune function in microglia. Furthermore, we will test whether the hormone-restored microglial functions can improve brain development and behavior in the mouse model of autism and form the basis for new treatment strategies.