Sex, glia, and development: Interactions in health and disease

This article is part of a Special Issue “Neuroendocrine-Immune Axis in Health and Disease.”Microglia and astrocytes are the primary immune cells within the central nervous system. Microglia influence processes including neural development, synaptic plasticity and cognition; while their activation and production of immune molecules can induce stereotyped sickness behaviors or pathologies including cognitive dysfunction. Given their role in health and disease, we propose that glia may also be a critical link in understanding the etiology of many neuropsychiatric disorders that present with a strong sex-bias in their symptoms or prevalence. Specifically, males are more likely to be diagnosed with disorders that have distinct developmental origins such as autism or schizophrenia. In contrast, females are more likely to be diagnosed with disorders that present later in life, after the onset of adolescence, such as depression and anxiety disorders. In this review we will summarize the evidence suggesting that sex differences in the colonization and function of glia within the normal developing brain may contribute to distinct windows of vulnerability between males and females. We will also highlight the current gaps in our knowledge as well as the future directions and considerations of research aimed at understanding the link between neuroimmune function and sex differences in mental health disorders.

► Glia, including astrocytes and microglia, are critical for brain development.
► Astrocytes are important for establishing sex differences in synaptic patterning.
► Neonatal male rats have significantly more microglia in brain regions than females.
► Adult female rats have more microglia in the same brain regions than males.
► Sex differences in glia may underlie vulnerabilities to particular disorders.