A P2RY12 deficiency results in sex-specific cellular perturbations and sexually dimorphic behavioral anomalies.

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.

Gender, status, and psychiatric labels.

We examine a key modified labeling theory proposition-that a psychiatric label increases vulnerability to competence-based criticism and rejection-within task- and collectively oriented dyads comprised of same-sex individuals with equivalent education. Drawing on empirical work that approximates these conditions, we expect the proposition to hold only among men. We also expect education, operationalized with college class standing, to moderate the effects of gender by reducing men's and increasing women's criticism and rejection. But, we also expect the effect of education to weaken when men work with a psychiatric patient. As predicted, men reject suggestions from teammates with a psychiatric history more frequently than they reject suggestions from other teammates, while women's resistance to influence is unaffected by their teammate's psychiatric status. Men also rate psychiatric patient teammates as less powerful but no lower in status than other teammates, while women's teammate assessments are unaffected by their teammate's psychiatric status. Also as predicted, education reduces men's resistance to influence when their teammate has no psychiatric history. Education also increases men's ratings of their teammate's power, as predicted, but has no effect on women's resistance to influence or teammate ratings. We discuss the implications of these findings for the modified labeling theory of mental illness and status characteristics theory.

A P2RY12 Deficiency Results in Sex-specific Cellular Perturbations and Sexually Dimorphic Behavioral Anomalies.

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.