Periodic dietary restriction reverses behavioral and neuronal alterations in a model of Alzheimer?s disease

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

Congreso; Buenos Aires AAIC Satellite Symposium | Alzheimer's Association; 2018

Alzheimer's Association

Dietary restriction (DR) has been shown to reduce the impact of age-associated diseases, probably through the modulation of energetic metabolism, inflammatory status and autophagy, among other pathways. In the present work, our objective was to evaluate neuroprotection and glial modulation as effects of DR in a mouse model of familial AD. Therefore, we established a protocol of periodic DR in control and PDAPP-J20 transgenic (TG) mice, that present cognitive and neuronal alterations since 5 months of age and plaque deposition since 8 months of age. Daily food consumption was restricted to 60% for 5 days/week every one week for a total of 6 weeks in 6.5 month-old mice. At 8 months of age, cognitive deficits were found in ad libitum-fed TG mice but not in the DR group. Interestingly, DR was associated with reduced hippocampal amyloid deposition. In parallel, hippocampal neurogenesis was decreased in TG mice under ad libitum diet whereas DR transgenic mice showed a neurogenic status similar to controls. Morphological signs of microglial activation were found in the hippocampus of ad libitum-fed TG mice but not in dietary restricted TG animals. Complementary, in vitro experiments were done on C6 astroglial cells exposed to AB with or without nutrient restriction. Subsequently, conditioned media (CM) from astrocytes were used to stimulate BV2 microglia. Nuclear translocation of NFkappaB in microglia was increased when exposed to CM from astrocytes incubated with AB but not from those exposed to AB and serum restriction. Our results suggest neuroprotective effects of nutrient restriction in AD, with modulation of glial activation as a potential pathway.