ArticleProceedings of the National Academy of Sciences of the United States of America2023
Microglia phagocytosis mediates the volume and function of the rat sexually dimorphic nucleus of the preoptic area.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Microglial IL-27 modulates depression-like behaviors induced by postnatal immune activation.Cell reports. Medicine · 2026Article
- Synaptic, cellular, and circuit mechanisms underlying sex differences in behaviors.Biology of sex differences · 2026Review
- Advancing insights into the neuroendocrine basis of socio-sexual interactions in mammals.Endocrinology · 2026Review
- Sex differences in microglia morphology and function across the lifespan are mediated by the early hormone environment.Brain, behavior, and immunity · 2026Article
- Article
- A male-dominant cell group expressing calbindin-D28K and androgen receptor in the mouse preoptic area requires postnatal testicular androgens and histone deacetylation.Journal of neuroendocrinology · 2025Article
- Morphological Sex Reversal in the Sexually Dimorphic Nucleus of the Preoptic Area in the Hypothalamus Delineated by Calbindin D28k-Immunoreactive Cell Clusters in YActa histochemica et cytochemica · 2025Article
- Emergence of the sex difference in calbindin D-28K neurons and the role of calbindin D-28K in clustering neurons of the preoptic area in mice.Cell and tissue research · 2025Article
- Microglial SWELL1 Deficiency Drives Male-Specific Seizure Vulnerability but Paradoxical Neuroprotection through Impaired Phagocytosis.bioRxiv : the preprint server for biology · 2025Article
- The role of estrogen in Alzheimer's disease pathogenesis and therapeutic potential in women.Molecular and cellular biochemistry · 2025Review
- Feminization of social play behavior depends on microglia.bioRxiv : the preprint server for biology · 2024Article
- A P2RY12 deficiency results in sex-specific cellular perturbations and sexually dimorphic behavioral anomalies.Journal of neuroinflammation · 2024Article
- Cell death by phagocytosis.Nature reviews. Immunology · 2024Review
- Microglial Phagocytosis During Embryonic and Postnatal Development.Advances in neurobiology · 2024Review
- Two-Step Actions of Testicular Androgens in the Organization of a Male-Specific Neural Pathway from the Medial Preoptic Area to the Ventral Tegmental Area for Modulating Sexually Motivated Behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Shadow imaging for panoptical visualization of brain tissue in vivo.Nature communications · 2023Article
- Contribution of birds to the study of sexual differentiation of brain and behavior.Hormones and behavior · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors.
Funding
Abstract
The sexually dimorphic nucleus of the preoptic area (SDN-POA) is the oldest and most robust sex difference reported in mammalian brain and is singular for its presence across a wide range of species from rodents to ungulates to man. This small collection of Nissl-dense neurons is reliably larger in volume in males. Despite its notoriety and intense interrogation, both the mechanism establishing the sex difference and the functional role of the SDN have remained elusive. Convergent evidence from rodent studies led to the conclusion that testicular androgens aromatized to estrogens are neuroprotective in males and that higher apoptosis (naturally occurring cell death) in females determines their smaller SDN. In several species, including humans, a smaller SDN correlates with a preference for mating with males. We report here that this volume difference is dependent upon a participatory role of phagocytic microglia which engulf more neurons in the female SDN and assure their destruction. Selectively blocking microglia phagocytosis temporarily spared neurons from apoptotic death and increased SDN volume in females without hormone treatment. Increasing the number of neurons in the SDN in neonatal females resulted in loss of preference for male odors in adulthood, an effect paralleled by dampened excitation of SDN neurons as evidenced by reduced immediate early gene (IEG) expression when exposed to male urine. Thus, the mechanism establishing a sex difference in SDN volume includes an essential role for microglia, and SDN function as a regulator of sexual partner preference is confirmed.
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