Protective effect of periodic dietary restriction on behavior and hippocampal deficits in a mouse model of Alzheimer?s disease

BEAUQUIS J; TODERO MF; POMILIO C; VINUESA A; GOROJOD R; ALAIMO, A; PORTE ALCON S; KOTLER M; SARAVIA F

Paris

Congreso; International Society for Neurochemistry; 2017

ISN

Alzheimer?s disease (AD) is a neurodegenerative pathologyassociated with progressive decline in cognition and brain functions.Accompanying amyloid b (AB) deposition, astrocytes and microglialose their neuroprotective functions and induce pathways thatamplify inflammation. Dietary restriction (DR) has been shown todecelerate the aging process and reduce the impact of age-associateddiseases, probably modulating oxidative and inflammatory status,regulating autophagy and inducing cell protection.Our objectives were to evaluate neuroprotective effects of DR ina model of familial AD and to parallelize in vivo results using anin vitro model of nutrient restriction on glial cells exposed to AB.We established a model of periodic DR in control and PDAPP-J20transgenic mice. Daily food consumption was restricted to 60% for5 days/week every one week for a total of 6 weeks.At 8 months of age, cognitive deficits and anxious-like behaviorwere found in ad libitum fed transgenic mice and were prevented byDR. In parallel, hippocampal neurogenesis was decreased intransgenic mice under ad libitum diet whereas transgenic miceunder DR showed a neurogenic status similar to controls. In vitroexperiments were done on C6 astroglial cells exposed to AB withand without nutrient restriction (FBS 2% vs. 10% in RPMI). Serumdeprivation and AB induced autophagy. Subsequently, conditionedmedia (CM) from C6 were used to stimulate BV2 microglia.