Sex-specific features of microglia from adult mice
Open accessAbstract
Sex has a role in the incidence and outcome of neurological illnesses, also influencing the response to treatments. Neuroinflammation is involved in the onset and progression of several neurological diseases, and the fact that estrogens have anti-inflammatory activity suggests that these hormones may be a determinant in the sex-dependent manifestation of brain pathologies. We describe significant differences in the transcriptome of adult male and female microglia, possibly originating from perinatal exposure to sex steroids. Microglia isolated from adult brains maintain the sex-specific features when put in culture or transplanted in the brain of the opposite sex. Female microglia are neuroprotective because they restrict the damage caused by acute focal cerebral ischemia. This study therefore provides insight into a distinct perspective on the mechanisms underscoring a sexual bias in the susceptibility to brain diseases.
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Sex has effects on microglial morphology, gene expression, and function.
“There is some precedent for sex having effects on microglial morphology, gene expression, and function. 33 , 34 , 35”
From Loss of <i>Inpp5d</i> has disease‐relevant and sex‐specific effects on glial transcriptomes (2024) · cites this paper as [35]
Gene expression of microglia differs between males and females.
“Additionally, gene expression of microglia differs between males and females [44, 45].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [45]
Heterogeneity of microglia between different brain areas and between different sexes is increasingly recognized.
“Heterogeneity of microglia between different brain areas (Grabert et al., 2016) and between different sexes (Villa et al., 2018) is increasingly recognized.”
From The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques (2019) · cites this paper as Villa et al., 2018
During normal physiological conditions, adult male mice tend to exhibit denser microglia in the hippocampus, cortex, and amygdala, whereas female rats typically display longer and more extensively branched microglial processes in the prefrontal cortex around adolescence.
“During normal physiological conditions, it has been shown that adult male mice tend to exhibit denser microglia in the hippocampus, cortex, and amygdala, whereas female rats typically display longer and more extensively branched microglial processes in the prefrontal cortex around adolescence, indicating possible differences in microglial surveillance between sexes, brain regions and time points [”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [45]
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Experimental — accuracy not yet measuredMicroglia show sex-specific differentiation and gene expression profiles in adult mice.
“Given that AD shows a sex-specific incidence and findings indicating that microglia show sex-specific differentiation and gene expression profiles in adult mice (27–29), we also examined whether there was a statistical interaction between AD diagnosis and sex (i.e., Gene expression = Diagnosis × Sex + covariates), using the covariate selections described above.”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [29]
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References 51 · Cited by 651
- Authors
- Villa, A., Gelosa, P., Castiglioni, L., Cimino, M., Rizzi, N., Pepe, G., Lolli, F., Marcello, E., Sironi, L., Vegeto, E., & Maggi, A.
- Affiliations
- University of Milan (IT)
- Centro Cardiologico Monzino (IT)
- University of Urbino (IT)
- Corresponding author
- Maggi, Adriana
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 23
- Issue
- 12
- Pages
- 3501-3511
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6024879
- OpenAlex
- W2808882111
- Cited by
- 651
- References
- 51
- Citations by year
- 2026: 84 · 2025: 76 · 2024: 87 · 2023: 75 · 2022: 90 · 2021: 100 · 2020: 72 · 2019: 51 · 2018: 16
- FWCI
- 27.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Funders
- European Union (ERC-2012-ADG322977-Ways)
- Seventh Framework Programme (278850)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- sex differences, microglia, microglial transcriptome, sex steroids, estrogen, neuroinflammation, neuroprotection, focal cerebral ischemia, sex-specific gene expression
- MeSH terms
- Aging, Animals, Brain, Brain Ischemia, Estradiol, Female, Gene Expression Regulation, Inflammation, Male, Mice, Inbred C57BL, Phenotype, Sex Characteristics, Rats, Sprague-Dawley, Microglia, Disease Progression, Stroke, Transcriptome
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