Microglial morphology and network composition is a visual signature of developmental plasticity and predicts pathological response

Le September 30 2026 at 09h00 Séminaire

Microglial morphology, as well as the spatial organization of their networks, are often treated as passive readouts of CNS pathology, yet they may equally shape its course. Understanding how these features develop and adapt could reveal therapeutic targets for CNS conditions marked by network dysfunction. We analyzed microglial morphologies in grey matter regions of C57BL/6J mice across postnatal development, identifying distinct routes of morphological maturation. Independently, microglial networks achieved spatial uniformity prior to individual morphological maturation. Recombinant CSF-1 or IL-34 application induced transient network remodeling whilst expanding accessible morphological states. Translating this framework to a mouse model of amyloid pathology, we linked microglial morphologies to local amyloid burden via plaque predictive morphological indices (PPMI). CSF-1 treatment elevated PPMI scores, correlating with reduced plaque burden, and induced morphology-related gene expression at the transcriptomic level. These findings establish that the microglial network follows defined paradigms of structural adaptation that determine disease-relevant function.