Immune activation during brain development results in sex differences in behavior: role of estrogen receptor signaling by Madeline Arnold

Madeline Arnold

UC Berkeley

I’m interested in how sex as a biological variable can impact complex systems. I’m studying how the immune system interacts with brain development, and how sex adds another layer of complexity in how the brain and behavior are altered by enviromental signals.

ABSTRACT

Sex differences in neurodevelopmental disorders, which are more common in males, give us a window into understanding how genetic and environmental variables regulate brain development. Immune activation during pregnancy has been linked to neurodevelopmental disorders such as autism. We can model this phenomenon via the maternal immune activation (MIA) mouse model, where pregnant dams are treated with the immune stimulatory molecule Poly(I:C) at E12.5. Interestingly, the resulting male offspring display behavioral changes not observed in the female offspring. To understand this sex difference, I am investigating the role of estrogen receptor beta (ERβ) as a candidate regulator which can respond to immune stimuli in a sex-specific manner. I generated a genetic mouse model deficient in ERβ in myeloid cells, and measured the behavior of females and males after MIA. By studying the role of ERβ in MIA, I hope to learn more about sex differences in neurodevelopmental disorders, as well as uncover basic science about how the immune system and sex-specific mechanisms play a role in development of the brain.

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