This page was translated automatically from Turkish. Read the original

This page is an AI-assisted Turkish summary of the study presented at the 26th World Congress of Psychiatry. The study belongs to the presenting authors; please refer to the original source when citing it.

Microglial deficiency in pathological brain development and function

Microglia deficiency in pathological brain development and functioning

Prefrontal microglial deficiency during adolescence leads to increased complement C4 in astrocytes and causes persistent synaptic and cognitive impairments in adulthood; these impairments do not develop when astrocytic C4 is silenced.

The study examines, through the lens of glial cells, how transient disruptions during sensitive periods translate into lasting dysfunction. The group's previous findings showed that transient microglial deficiency in the prefrontal cortex (PFC) during adolescence, but not adulthood, leads to persistent synaptic and cognitive impairments, identifying adolescence as a critical window for microglia-dependent circuit maturation. In this study, this transient microglial deficiency is shown to cause a maladaptive increase in complement component C4 levels in prefrontal astrocytes. Silencing astrocytic C4 using short hairpin RNA (shRNA), or eliminating it through an astrocyte-specific conditional knockout, prevented the emergence in adulthood of the synaptic and cognitive impairments caused by prefrontal microglial deficiency during adolescence. In parallel, chemogenetic stimulation of prefrontal astrocytes during adolescence led to a transient increase in astrocytic C4 expression and enhanced microglia-mediated synaptic pruning, and was sufficient on its own to reproduce the synaptic and cognitive impairments in adulthood. Similar increases in astrocytic C4 and associated phenotypes were also observed in a mouse model of maternal immune activation (MIA), an environmental risk factor for neurodevelopmental disorders. The findings identify a pathological microglia–astrocyte signaling axis that converges on a maladaptive increase in C4 during adolescence and demonstrate that this axis leads to lasting impairments in prefrontal circuit function.

All WCP 2026 summaries