Sexual Dimorphism of Dopaminergic Neurons and Microglia in The Basal Ganglia of Adult Mice

Abstract

Differences between male and female brains are correlated with sex-specific variation in behaviour and vulnerability to neuropsychiatric diseases. The basal ganglia play a pivotal role in regulating motor and executive functions as well as emotions. Although the basal ganglia contain a high density of receptors for sex hormones, scarce data are available about the sexual dimorphism of cell populations within the basal ganglia. The present study aims to investigate sex-specific differences in two cell populations within the basal ganglia including the dopaminergic neurons and the microglia. Thus, we assessed the optical density of the dopaminergic neurons within the substantia nigra and their projections to the caudate-putamen and globus pallidus by tyrosine hydroxylase immunohistochemistry as well as the density and morphology of IBA-1-expressing microglia in adult (3-months-old) male and female mice. We demonstrated that the substantia nigra contains a higher density of dopaminergic neurons in female mice, with more intensively stained projections in caudate-putamen and globus pallidus. The female substantia nigra and globus pallidus showed an increased number of microglia. Additionally, the microglia exhibited an activated morphology with increased complexity in the female globus pallidus. Our data provide novel anatomical and structural evidence for sex-dependent differences in basal ganglia neuronal circuits and, consequently, the susceptibility to neurological disorders, e.g., Parkinson’s disease. This may help a better understanding of the neuropathological diversities and may allow for the design of personalised therapeutic approaches for better treatment outcomes in males and females.