Sex differences in microglial colonization of the developing rat brain

Abstract

Microglia are the resident immune cells within the brain and their production of immune molecules such as cytokines and chemokines is critical for the processes of normal brain development including neurogenesis, axonal migration, synapse formation, and programmed cell death. Notably, sex differences exist in many of these processes throughout brain development; however, it is unknown whether a sex difference concurrently exists in the colonization, number, or morphology of microglia within the developing brain. We demonstrate for the first time that the number and morphology of microglia throughout development is dependent upon the sex and age of the individual, as well as the brain region of interest. Males have overall more microglia early in postnatal development (postnatal day (P) 4), whereas females have more microglia with an activated/amoeboid morphology later in development, as juveniles and adults (P30-60). Finally, gene expression of a large number of cytokines, chemokines and their receptors shifts dramatically over development, and is highly dependent upon sex. Taken together, these data warrant further research into the role that sex-dependent mechanisms may play in microglial colonization, number, and function, and their potential contribution to neural development, function, or potential dysfunction.

In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with18F-PBR111 PET

“…Studies in rodents suggested a higher number of microglia and astrocytes in adult females (36,37), so we cannot exclude the possibility that a higher prevalence of women in the MS group may have contributed to the higher 18 F-PBR111 V T in patients.…”

Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

“…Furthermore, as different areas of the brain develop at different time points in the neonatal period, this may result in different long term effects, depending upon the time of inflammation. Even the immune competent microglia in the brain appear at different times in different structures; for example the hypothalamus and the hippocampus vary significantly in microglia number in early development (Schwarz et al, 2012).…”

The impact of early life immune challenge on behavior and microglia during postnatal development

“…Certainly, microglia are emerging as a key regulator of CNS development and in particular, evidence is building that sex differences in microglia during early postnatal life may contribute to long-term sex differences in brain function. [36][37][38] Microglia numbers are increased in the early postnatal period, compared to adolescence and adulthood, with peak numbers occurring in the second week of postnatal life with a gradual reduction in number in the following weeks [39] . The morphology of microglia in the first postnatal week in rodents is consistent with activated ameboid microglia found in the adult CNS [24,38,39] .…”