Periodic dietary restriction modulates behavior and hippocampal déficits in an animal model of Alzheimer?s Disease

MARÍA FLORENCIA TODERO; CARLOS POMILIO; ÁNGELES VINUESA; ROXANA GOROJOD; AGUSTINA ALAIMO; SOLEDAD PORTE ALCÓN; MÓNICA KOTLER; FLAVIA SARAVIA; BEAUQUIS JUAN

Congreso; International Society for Neurochemistry Meeting; 2017

Alzheimer?s disease (AD) is a neurodegenerative pathology associated with progressive decline in cognition and brain functions. Accompanying amyloid β (AB) deposition, astrocytes and microglia lose their neuroprotective functions and induce pathways that amplify inflammation. Dietary restriction (DR) has been shown to decelerate the aging process and reduce the impact of age-associated diseases, probably modulating oxidative and inflammatory status, regulating autophagy and inducing cell protection. Our objectives were to evaluate neuroprotective effects of DR in a model of familial AD and to parallelize in vivo results using an in vitro model of nutrient restriction on glial cells exposed to AB. We established a model of periodic DR in control and PDAPP-J20 transgenic mice. Daily food consumption was restricted to 60% for 5 days/week every one week for a total of 6 weeks. At 8 months of age, cognitive deficits and anxious-like behavior were found in ad libitum fed transgenic mice and were prevented by DR. In parallel, hippocampal neurogenesis was decreased in transgenic mice under ad libitum diet whereas transgenic mice under DR showed a neurogenic status similar to controls. In vitro experiments were done on C6 astroglial cells exposed to AB with and without nutrient restriction (FBS 2% vs. 10% in RPMI). Serum deprivation and AB induced autophagy. Subsequently, conditioned media (CM) from C6 were used to stimulate BV2 microglia. Microglial NFkappaB nuclear translocation was increased when exposed to CM from C6 cells with ABeta but not from C6 cells exposed to AB and serum restriction. Our results suggest neuroprotective effects of nutrient restriction in the context of AD, with glial activation and autophagy as potentially involved pathways.