[AVX Seminar] Mechanisms of glia homeostasis: implications for neurological disease

AVX Seminar

Title: Mechanisms of glia homeostasis: implications for neurological disease

Speaker: João Relvas

Affiliation: Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto

Abstract:

Microglia, the largest myeloid resident cell population in the brain, are critical for nervous tissue homeostasis. I will show that microglia-specific ablation of the small GTPase RhoA induces microglia neurotoxic polarization leading to the manifestation of phenotypic hallmarks associated with  neurodegenerative disorders. Ablation of RhoA induces microglia neurotoxic polarization via downregulation of C-terminal Src kinase (Csk) leading to Src hyperphosphorylation and overactivation, suggesting that the  RhoA/Csk/Src pathway is critical for microglia homeostasis. Accordingly, we also show that this pathway is  dysregulated early in a mouse model of Alzheimer´s disease,  before plaque formation.

Overall,  our data provide additional support to the emergent notion of “microgliopathy”, in which microglia dysfunction, by itself, can initiate or be the primary cause of brain disease.