ASTROGLIAL ACTIVATION AND INSULIN RESISTANCE COMPRISE A JOINT RESPONSE IN EXPERIMENTAL ALZHEIMER’S DISEASE

BENTIVEGNA M; GREGOSA A; POMILIO C; VINUESA A; GONZALEZ PEREZ N; PRESA J; BELLOTTO M; LUX-LANTOS V; SARAVIA F; BEAUQUIS J

Porto

Congreso; ISN-ESN 2023 Meeting Porto, Portugal, 8-11 August 2023; 2023

International Society for Neurochemistry

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease and the leading cause of dementia. Besides amyloid beta (Aβ) and tau accumulation, inflammation and insulin resistance are common findings in AD brains. Astrocytes regulate these processes, maintaining brain homeostasis and coordinating the inflammatory response. In the present work, our objectives were 1) to study the metabolic and inflammatory status of the PDAPP-J20 transgenic (TG) mouse, model of AD, and 2) to evaluate astroglial activation and insulin signaling upon Aβ exposure. We hypothesized that in AD, astrocytes adopt a phenotype that promotes inflammation and lose homeostatic functions. Evaluation in the open-field test showed an anxious-like behavior in TG mice. Insulin signaling measured by the pAkt/Akt ratio was impaired in the hippocampus (p