Increased Complement C4 in a Sparse Neuronal Subset Induces Network-Wide Transcriptomic Alterations in the Prefrontal Cortex.

ABSTRACT: The complement (C) pathway, a vital part of innate immunity, defends against pathogens and supports tissue surveillance. While local activation in the periphery enhances immune protection, dysregulation can trigger a self-amplifying cascade that spreads beyond the initial site, resulting in tissue injury. In the brain, complement proteins regulate synaptic plasticity and connectivity, raising the possibility that similar mechanisms of maladaptive propagation may disrupt neural circuits under pathological conditions. Although complement dysregulation is linked to neurological and psychiatric disorders, the impact of localized upregulation in a small subset of cells on broader cortical networks remains unclear. To examine this, we overexpressed the schizophrenia (SCZ) risk gene C4 (C4-OE) in

SUBMITTER: Bolshakova S 

PROVIDER: S-EPMC12154845 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature