Influence of Androgens on the Amygdala

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DESCRIPTION (provided by applicant): The objective of this line of research is to understand how sex differences in the brain arise and the neuroanatomical nature of these sex differences. Public health is affected by numerous mental diseases which appear more frequently in one sex than the other, suggesting sex differences in neural anatomy make one sex more susceptible to particular abnormalities and less susceptible to others. The amygdala demonstrates sex differences in activity and anatomy and is closely linked to several sex-biased public health concerns such as schizophrenia, autism, anxiety, depression, and bi-polar disorder. The medial postero-dorsal amygdala (MePD) appears especially sensitive to sex hormones and challenges the accepted theory that neural sex differences are estrogen-dependent. In the MePD androgen receptors (AR) are necessary for complete formation of sex differences in several aspects of neural anatomy including regional volume, neuronal soma size, and neuron number. However, other aspects of MePD cellular anatomy may also contribute to sex differences in the amygdala. In other sexually dimorphic brain regions, astrocytes interact with local GABA neurons to produce changes in cell morphology. This interaction is mediated by sex hormones and it is likely that a similar relationship may exist in the MePD. We have recently identified dramatic sex and hemisphere differences in astrocyte number and morphology in the MePD as part of a prior proposal. Building upon that discovery, this research will 1) utilize immunocytochemistry and stereology to count and trace the soma of GABA containing neurons within the MePD, looking for sex difference in GABA neuron number or size 3) assess the influence of adult androgen manipulations on astrocytes and GABA neurons and 4) utilize fluorescent labeling and confocal microscopy to identify which cell types contain AR, thus determining where androgens are acting in the MePD. 2. A cursory examination of mental disorder prevalences reveals strong sex-biases in numerous pathologies, suggesting sex-differences in how the brain functions. By exploring how male and female brains are different and how these differences arise, we may be able to develop more targeted and effective treatments for such diseases. This research focuses on a region of the brain that is both highly sensitive to sex hormones and closely linked to a multitude of sex-biased diseases, the amygdala. This research also targets specific cell types in order to identify where sex hormones are acting to alter amygdala neural anatomy.