Effects of periodic dietary restriction on behavioral, glial and neuronal alterations in an animal model of Alzheimer?s disease.

CARLOS POMILIO; PRESA, JESSICA; JUAN BEAUQUIS; CARLOS POMILIO; PRESA, JESSICA; JUAN BEAUQUIS; GREGOSA, AMAL; ANGELES VINUESA; DIEGO EGOBURO; GREGOSA, AMAL; MARÍA FLORENCIA TODERO; ANGELES VINUESA; MELISA BENTIVEGNA; DIEGO EGOBURO; FLAVIA E. SARAVIA; MARÍA FLORENCIA TODERO; MELISA BENTIVEGNA; FLAVIA E. SARAVIA

Valdivia

Congreso; International Conference on Brain and Energy Metabolism; 2018

Alzheimer?s disease (AD) is a neurodegenerative pathology associated with progressive decline in cognition and brain function. On early AD stages, astrocytes and microglia lose neuroprotective functions and promote inflammation, even before amyloid β (AB) deposition. Dietary restriction (DR) has been shown to reduce the impact of age-associated diseases, probably modulating energetic metabolism, oxidative and inflammatory status and autophagy. Our objective was to evaluate neuroprotective effects of DR in a model of familial AD. Therefore, 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 in 6.5 month-old mice. At 8 months of age, cognitive deficits were found in ad libitum-fed transgenic mice and were prevented by DR. Also, DR was associated with reduced hippocampal amyloid deposition. In parallel, hippocampal neurogenesis was decreased in transgenic mice under ad libitum diet whereas DR transgenic mice showed a neurogenic status similar to controls. Complementary, in vitro experiments were done on C6 astroglial cells exposed to AB with and without nutrient restriction. Both serum deprivation and AB induced autophagy. Further, we evaluated astroglial glycogen storages through PAS technique and lactate flux in the presence of AB and/or nutrient deprivation. 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.