Microglia express distinct M1 and M2 phenotypic markers in the postnatal and adult central nervous system in male and female mice.
TLDR
Age‐ and sex‐specific variances in basal gene expression may allow differential microglial responses to the same stimulus at different ages, perhaps contributing to altered CNS vulnerabilities and/or disease courses.Abstract:
Although microglial activation is associated with all CNS disorders, many of which are sexually dimorphic or age-dependent, little is known about whether microglial basal gene expression is altered with age in the healthy CNS or whether it is sex dependent. Analysis of microglia from the brains of 3-day (P3)- to 12-month-old male and female C57Bl/6 mice revealed distinct gene expression profiles during postnatal development that differ significantly from those in adulthood. Microglia at P3 are characterized by relatively high iNOS, TNFα and arginase-I mRNA levels, whereas P21 microglia have increased expression of CD11b, TLR4, and FcRγI. Adult microglia (2-4 months) are characterized by low proinflammatory cytokine expression, which increases by 12 months of age. Age-dependent differences in gene expression suggest that microglia likely undergo phenotypic changes during ontogenesis, although in the healthy brain they did not express exclusively either M1 or M2 phenotypic markers at any time. Interestingly, microglia were sexually dimorphic only at P3, when females had higher expression of inflammatory cytokines than males, although there were no sex differences in estrogen receptor expression at this or any other time evaluated here. Compared with microglia in vivo, primary microglia prepared from P3 mice had considerably altered gene expression, with higher levels of TNFα, CD11b, arginase-I, and VEGF, suggesting that culturing may significantly alter microglial properties. In conclusion, age- and sex-specific variances in basal gene expression may allow differential microglial responses to the same stimulus at different ages, perhaps contributing to altered CNS vulnerabilities and/or disease courses.read more
Citations
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Sexually divergent induction of microglial-associated neuroinflammation with hippocampal aging
Colleen A. Mangold,Benjamin Wronowski,Mei Rong Du,Dustin R. Masser,Niran Hadad,Georgina V. Bixler,Robert M. Brucklacher,Matthew M. Ford,William E. Sonntag,Willard M. Freeman +9 more
TL;DR: These findings demonstrate sexually divergent neuroinflammation with aging that may contribute to sex differences in age-related neurological diseases such as stroke and Alzheimer’s, specifically in the complement system.
Journal ArticleDOI
Sexually dimorphic outcomes and inflammatory responses in hypoxic-ischemic encephalopathy
TL;DR: HIE leads to an equivalent primary brain injury in male and female neonates at the acute stage that develops into sexually dimorphic outcomes at later time points and an innate immune response secondary to the primary injury may contribute to sexual dimorphism in HIE.
Journal ArticleDOI
Sex differences in microglial phagocytosis in the neonatal hippocampus.
TL;DR: The data show that there are important sex differences in microglia function in the hippocampus during the early neonatal period, and that estradiol treatment increased microglial proliferation in females.
Journal ArticleDOI
Microglial numbers attain adult levels after undergoing a rapid decrease in cell number in the third postnatal week
Maria Nikodemova,Rebecca S. Kimyon,Ishani De,Alissa L. Small,Lara S. Collier,Jyoti J. Watters +5 more
TL;DR: It was found that after an initial increase during the first 14 postnatal days, microglial numbers in mouse brain began declining in the third postnatal week and were reduced by 50% by 6weeks of age; these "adult" levels were maintained until at least 9months of age.
Journal ArticleDOI
Inflammatory microglia are glycolytic and iron retentive and typify the microglia in APP/PS1 mice.
R. Holland,A. McIntosh,Orla M. Finucane,Virginia Mela,Ana Rubio-Araiz,G. Timmons,Sarah A McCarthy,Yurii K. Gun'ko,Marina A. Lynch +8 more
TL;DR: Analysis of microglia prepared from wildtype mice and from transgenic mice that overexpress amyloid precursor protein and presenilin 1 revealed genotype-related increases in glycolysis, accompanied by increased PFKFB3, and an increase in the expression of ferritin suggesting that increased intracellular iron concentration may drive the metabolic and/or inflammatory changes.
References
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