Figure 3: New view of sexual differentiation of the brain involving immune modulators.

Converging evidence from studies exploring the cellular and molecular mechanisms establishing sex differences in brain and behavior implicates the innate immune cells of the brain, microglia, as well as mast cells which are found both in the periphery and centrally. Males consistently have either more of these immune cells in specific brain regions or the cells are in a more activated state and producing inflammatory signaling molecules are engaging in high levels of phagocytosis during the critical period for sexual differentiation, thereby modulating divers endpoints such as synaptogenesis and cell survival. Cytokines and associated proteins are also expressed at higher levels in males and in one brain region result in the death of neurons that would otherwise survive. Thus there both a complexity and a consistency in the involvement of the immune system in masculinization of brain and behavior in rodents.