ArticleJournal of neuroinflammation2024
A P2RY12 deficiency results in sex-specific cellular perturbations and sexually dimorphic behavioral anomalies.
Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Differential effects of P2Y12 inhibition on sleep and glymphatic function in male and female mice.Brain, behavior, & immunity - health · 2026Article
- Microglial SWELL1 deficiency drives male-specific seizure vulnerability but paradoxical neuroprotection through impaired phagocytosis.JCI insight · 2026Article
- KDM5C and KDM5D influence DNA methylation in adult mouse liver.Biology of sex differences · 2026Article
- Memory deficits in hypertensive ApoE4 mice reversed by P2Y12 inhibition via different mechanisms in males and perimenopausal females.Research square · 2025Article
- Knockout of P2Y12 receptor facilitates neuronal envelopment by reactive microglia and accelerates prion disease.Journal of neuroinflammation · 2025Article
- The effects of P2Y12 loss on microglial gene expression, dynamics, and injury response in the cerebellum and cerebral cortex.Brain, behavior, and immunity · 2025Article
- Microglial SWELL1 Deficiency Drives Male-Specific Seizure Vulnerability but Paradoxical Neuroprotection through Impaired Phagocytosis.bioRxiv : the preprint server for biology · 2025Article
- Knockout of P2Y12 receptor facilitates microglia-neuron body-to-body interactions and accelerates prion disease.bioRxiv : the preprint server for biology · 2025Article
- Biological sex, microglial signaling pathways, and radiation exposure shape cortical proteomic profiles and behavior in mice.Brain, behavior, & immunity - health · 2025Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Microglia are sexually dimorphic, yet, this critical aspect is often overlooked in neuroscientific studies. Decades of research have revealed the dynamic nature of microglial-neuronal interactions, but seldom consider how this dynamism varies with microglial sex differences, leaving a significant gap in our knowledge. This study focuses on P2RY12, a highly expressed microglial signature gene that mediates microglial-neuronal interactions, we show that adult females have a significantly higher expression of the receptor than adult male microglia. We further demonstrate that a genetic deletion of P2RY12 induces sex-specific cellular perturbations with microglia and neurons in females more significantly affected. Correspondingly, female mice lacking P2RY12 exhibit unique behavioral anomalies not observed in male counterparts. These findings underscore the critical, sex-specific roles of P2RY12 in microglial-neuronal interactions, offering new insights into basal interactions and potential implications for CNS disease mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.