Producción CyT

Revista Medicina - Nutrient restriction regulates autophagy and amyloid beta content in astrocytes in vitro

Congreso

Autoría:

Amal Gregosa ; Melisa Bentivegna ; Angeles Vinuesa ; Carlos Javier Pomilio ; Jessica Presa ; Melina Paula Bellotto ; GONZALEZ PEREZ, NICOLAS GABRIEL ; Flavia Saravia ; Juan Beauquis

Fecha:

2023

Editorial y Lugar de Edición:

Sociedad Argentina de Investigaciones Clinicas

Resumen *

Nutrient restriction is associated with increased lifespan and prevention of chronic diseases in various organisms. Previously, we reported that dietary restriction (DR) decreased hippocampal amyloid load, increased neurogenesis, and improved cognitive performance in mice modeling Alzheimer?s disease (PDAPP-J20 strain, TG). Astroglial autophagy was studied as a potential mechanism involved in amyloid beta (AB) clearance. We found increased LC3 and p62 labeling in hippocampal astrocytes, suggesting blocked autophagy in TG mice. In vitro results showed that astroglial AB content was decreased after NR normalized LC3 levels. In the present study, our aim was 1) to evaluate in depth how astroglial autophagy is modulated in mice along a DR period (5 days with 60% of the habitual food intake) and 2) to analyze the autophagic flux in an in vitro model exposed to AB 1-42 peptides and nutrient restriction (NR). Adult C57BL/6 mice showed increased ketonemia after DR (p<0.01 vs. baseline), evidencing a fasting-like condition. Rab 7 protein levels in the hippocampus (immunoblot) showed a tendency to increase in animals exposed to DR (p=0.0508). These results support possible induced autophagy by DR period. In vitro, we exposed the astrocytic C6 rat cell line to AB 1-42 peptides and incubated them in NR or control media (2% vs. 10% FBS). We performed a Cyto ID assay to evaluate autophagosome levels and found increased fluorescence in AB-exposed cells compared with control (CTL vs AB, p<0.05).Interestingly, this effect was prevented in AB-exposed cells incubated under NR, suggesting a normalization of the autophagic flux. In conclusion, a 40% DR modulates hippocampal autophagy in adult mice, indicating a potential pathway for DR-associated increased AB clearance. Our in vitro results suggest that NR prevents the AB-associated blockage of the astroglial autophagic flux. We plan to perform mechanistic studies to determine which point of the autophagy pathway is modulated by NR. Información suministrada por el agente en SIGEVA

Palabras Clave

ASTROCYTESAUTOPHAGYAMYLOIDRESTRICTION