METFORMIN REDUCES INFLAMMATORY RESPONSE AND RESTORES MICROGLIAL PROTEOSTASIS AND MITOCHONDRIAL STATUS IN EXPERIMENTAL MODELS OF TYPE 2 DIABETES MELLITUS

GONZÁLEZ PÉREZ, N.; BENTIVEGNA, M.; ARCUCCI, L.; BELLOTTO, M.; PRESA, J.; BEAUQUIS, J.; SARAVIA, F.; POMILIO, C.

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2023

Type 2 diabetes is a metabolic disorder associated with cognitive dysfunction and a higher risk of developing Alzheimer’s disease, being two highly prevalent disorders worldwide. Neuroinflammation mediated by microglial activation in the brain can lead to neuronal damage and cognitive impairment. Metformin is the primary drug for T2D treatment, but its effects on the brain and microglial cells are unknow. Our aim was to evaluate the therapeutic potential of metformin employing in vivo and in vitro experimental models that parallel some of the metabolic changes observed in T2D. In mice exposed to a high-fat diet (HFD) during 4 months since weaning -inducing insulin resistance along with neuroinflammation- systemic metformin administration (240 mg/kg i.p, 9 injections during 3 weeks) was found to diminish peripheral insulin resistance assessed by WB against AKT in liver. In the brain, metformin administration induced a reduction on microglial reactivity evaluated as soma size (p