Uncovering sex differences of rodent microglia
Open accessAbstract
There are inherent structural and functional differences in the central nervous systems (CNS) of females and males. It has been gradually established that these sex-specific differences are due to a spectrum of genetic, epigenetic, and hormonal factors which actively contribute to the differential incidences, disease courses, and even outcomes of CNS diseases between sexes. Microglia, as principle resident macrophages in the CNS, play a crucial role in both CNS physiology and pathology. However, sex differences of microglia have been relatively unexplored until recently. Emerging data has convincingly demonstrated the existence of sex-dependent structural and functional differences of rodent microglia, consequently changing our current understanding of these versatile cells. In this review, we attempt to comprehensively outline the current advances revealing microglial sex differences in rodent and their potential implications for specific CNS diseases with a stark sex difference. A detailed understanding of molecular processes underlying microglial sex differences is of major importance in design of translational sex- and microglia-specific therapeutic approaches.
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Sex differences in microglia have been reported in both rodents and humans.
“Sex differences in microglia have been reported in both rodents and humans66”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [66]
The Abstract and the section on microglial morphology and numbers through development report sex differences in rodent microglia. The review focuses on rodents; the passages found do not report corresponding differences in human microglia, so the human part of the claim is unsupported by this paper. (LLM, conf=0.87)
Experimental — accuracy not yet measuredInnate differences between male and female microglia are exacerbated during immune challenge and stress and are suggested to be a prominent influence in observed sex biases of neurological disease.
“Importantly, these innate differences are exacerbated during immune challenge and stress and are suggested to be a prominent influence in observed sex biases of neurological disease34,36,68,69.”
From Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system (2023) · cites this paper as [36]
In “Sex differences of microglia in response to exogenous stimuli” (page unavailable), the review reports a sex difference after inflammatory stimulation where unstimulated microglia had similar levels, and describes sex-specific responses to stress. It does not establish that stress exacerbates pre-existing differences. The Conclusions suggest microglial differences may contribute to sex biases in neurological disease, but describe them as a possible partial influence rather than a prominent one. (LLM, conf=0.82)
Experimental — accuracy not yet measuredPrevious reports indicate sexual dimorphism in microglial genetics.
“based on previous reports of sexual dimorphism in microglial genetics34–36”
From Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system (2023) · cites this paper as [36]
Mouse cohorts in this study were balanced for sex.
“Mouse cohorts in this study were balanced for sex based on previous reports of sexual dimorphism in microglial genetics34–36.”
From Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system (2023) · cites this paper as [36]
Aspects of sexual dimorphism in microglial gene expression are region-dependent.
“In addition, aspects of sexual dimorphism in microglial gene expression are region-dependent36,68.”
From Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system (2023) · cites this paper as [36]
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- Authors
- Han, J., Fan, Y., Zhou, K., Blomgren, K., & Harris, R. A.
- Affiliations
- Karolinska University Hospital (SE)
- Karolinska Institutet (SE)
- Corresponding author
- Han, Jinming
- Harris, Robert A.
- Venue
- Journal of Neuroinflammation
- Published
- 2021-03-17
- Volume
- 18
- Issue
- 1
- Pages
- 74-74
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC7972194
- OpenAlex
- W3136882251
- Cited by
- 224
- References
- 111
- Citations by year
- 2026: 45 · 2025: 45 · 2024: 50 · 2023: 36 · 2022: 40 · 2021: 8
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- China Scholarship Council
- the Swedish Research Council
- Neuroforbundet
- Hjärnfonden
- Alzheimerfonden
- Alltid Litt Sterkere
- the Swedish Cancer Foundation
- the Swedish Childhood Cancer Fund
- 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 › Molecular Biology › Inflammasome and immune disorders
- Keywords
- sex differences, microglia, rodent models, central nervous system, sex hormones, epigenetics, central nervous system disorders, sex-specific treatment
- MeSH terms
- Animals, Female, Male, Rodentia, Sex Characteristics, Microglia, Epigenesis, Genetic
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