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Table 2 Overview of studies comparing the functional differences between male and female microglia

From: Uncovering sex differences of rodent microglia

Species Age Main functional differences References
C57BL/6 mice and NF-κB-luc2 mice 12 weeks Male microglia express more NF-κB regulated genes and are more prone to inflammatory activation than are females. These differences can also be maintained in vitro and thus do not totally depend on sex steroids. Females can even maintain sex-specific microglial differences when transplanted into the opposite sex brain, and this protects the males from ischemic stroke. [62]
Csf1R-EGFP mice 13 weeks Sex differences of electrophysiological responses to ATP which measured as membrane currents were noted in isolated microglia. Male microglia have a higher antigen-presenting capacity compared to females. The expression of MHCI was higher in male microglia in both the cortex and hippocampus, while MHCII expression was higher in male cortical microglia. [52]
C57BL/6 mice 13 weeks Transcriptional profile differences were found between isolated male and female microglia in both the hippocampus and cortex. Sex differences of microglial steady-state protein levels were also noted from the whole brain. [52]
CD1 mice E3,5; adolescent and adult Treatment of CSF1R inhibitor to deplete embryonic microglia cause sex-specific effects on mice, evidenced by adolescent female mice showing hyperactive development and adult female mice showing anxiolytic-like behavior. However, these phenomena were not noted in male adolescent and adult mice respectively. [10]
C57BL6/J mice
CX3CR1gfp/gfp knock-in mice
18 weeks There are sex differences of hypothalamic microglial CX3CR1 signaling activation which contribute to obesity susceptibility between male and female mice. Female mice are more resistant to diet-induced obesity than are males. In contrast, female mice become susceptible to diet-induced obesity in the absence of CX3CR1 signaling. [63]
Sprague Dawley rats 60–90 days Rat female microglia in the periaqueductal gray area exhibited a more activated phenotype at baseline, produced higher transcription levels of IL-1β, and could be more responsive to immune challenges such as LPS than were male rats, without overall microglial gender density differences in this region. [64]
Wistar rats Newborn (P0) to P2 Cultured female rat newborn microglia had higher phagocytic activity than in males as measured by in vitro bead intake assays at both baseline and following by IFNγ stimulation. In contrast, female rat newborn microglia had less basal and stimulated microglial migration than the males as measured by in vitro Transwell assay. [16]
Sprague Dawley rats Neonatal During early postnatal development, phagocytic female microglia in the hippocampus had significantly more highly expressed phagocytic pathway genes and phagocytic associated functions when compared to the males. [53]
C57BL/6 SPF and GF mice E18.5
P60
Microglia exert a sex-specific effect on long-term absence of the microbiome, with males being significantly affected during early development while females exhibited profound changes in adulthood instead. [26]
Sprague Dawley rats Around 70 days old Acute or chronic behavioral stress has distinct direct effects on corticolimbic microglial morphology and immune factor transcriptional expression such as CD40, CX3CR1, and CD200R in a number of brain regions which is mediated by microglia in a sex-dependent manner. [65]
Sprague Dawley rats Around 70 days old Differential effects of stress on microglial cell activation in male and female medial prefrontal cortex [66]
Sprague Dawley rats P1 and P21 Cultured rat male microglia had increased migration compared to females after single IL-4 stimulation. The mRNA level of K+ channel (Kcna3) and Kv current were also higher in male P21 microglia than in females after inflammatory stimulation, while unstimulated microglia had similar levels in males and females. [67]
C57BI/6J mice 17–18 months Female aged microglia exhibited higher expression of translocator protein and higher expression of M1 markers following peripheral LPS challenge than did male aged microglia. [68]
  1. Abbreviations: NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells, Csf1R colony-stimulating factor 1 receptor, ATP adenosine triphosphate, MHC major histocompatibility complex, E3,5 embryonic day 3.5, CX3CR1 CX3C chemokine receptor 1, LPS lipopolysaccharide, IL-1β interleukin-1beta, IFNγ interferon-γ, GF germ-free, SPF specific-pathogen free
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