Modulation of glial autophagy by periodic dietary restriction as a potential therapeutic strategy in an animal model of Alzheimer?s disease.

POMILIO C; SARAVIA F; VINUESA A; PRESA JESSICA; VINUESA A; PRESA JESSICA; GREGOSA A; BENTIVEGNA M; BEAUQUIS J; GREGOSA A; BENTIVEGNA M; BEAUQUIS J; POMILIO C; SARAVIA F

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Sociedad Argentina de Investigación Clínica (SAIC)

Alzheimer?s disease (AD) is the leading cause of dementia for which there are no effectivetreatments. Dietary restriction (DR) has been proposed as a potential therapeutic strategy for age-associated diseases. Our objectives were to analyze memory and hippocampal alterations in ananimal model of familial AD, the PDAPP-J20 transgenic mouse (Tg) and to evaluate the effects of aperiodic DR protocol (3 cycles of 40% DR for 5 days and ad libitum (AL) diet for 9 days). Weobserved cognitive impairment, impaired adult neurogenesis and progressive amyloid beta (AB)deposition in the hippocampus of AL-fed Tg mice. Periodic DR was associated to cognitiveimprovement, increased hippocampal neurogenesis, and reduced hippocampal amyloid load.Through immunofluorescence for LC3 (autophagosomes) and GFAP (astrocytes), we found thatautophagy is modulated in Tg mice with a high proportion of LC3 localized in astrocytes. We alsofound that astrocytes contained AB co-localizing with LC3. From these results we hypothesized thatthe reduction in amyloid plaques associated to DR would be partly mediated by astroglialautophagy. Therefore, we evaluated the C6 astrocyte line exposed to fibrillar beta amyloid (fAB, 2,6 or 24h) and previously nutrient restricted (NR; 2% FBS) or not (10% FBS) for 6h. Exposure to fABfor 2h showed that LC3 was increased after bafilomycin treatment, an inhibitor of autophagosome-lysosome fusion, indicating a functional autophagy (AB NR vs AB NR BAF, p