Sex Differences in the Brain

It has long been appreciated that the nervous system is distinct in males and females. These sexually-dimorphic differences are relevant to NF1 brain tumors and autism. Whereas both girls and boys with NF1 develop optic gliomas, girls are 3 times more likely to experience visual decline from their tumors. In addition, autism is 3 times more common in boys in the general population, while in children with NF1 is only slightly more frequent in boys.

Using genetically-engineered mice, we begun to identify the cellular and molecular reasons that underlie these sexually-dimorphic differences. As such, we found greater microglia activation and neuronal damage in female mice with optic glioma, which results from estrogen regulation of immune system function. In addition, we discovered lower cyclic AMP levels in the neurons from female Nf1 mutant mice, which is not related to estrogen, and makes these nerve cells more susceptible to injury and death.

Current projects in the Gutmann research laboratory are focused on defining the molecular and cellular basis for the sexual dimorphism observed in NF1-associated optic glioma and autism.