Modulation of glial response by dietary restriction in an animal model of Alzheimer?s disease

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

Ciudad Autónoma de Buenos Aires

Congreso; 2nd FALAN Congress 2016; 2016

Dietary restriction (DR) has been shown to decelerate the aging process and to reduce age-associated diseases in several species. Our objectives are 1) to establish an animal model of DR, 2) to study potential neuroprotective and anti-inflammatory effects of DR in a murine model of familial Alzheimer?s disease (AD), and 3) to parallelize in vivo results using an in vitro model of nutrient restriction on glial cells exposed to amyloid beta (ABeta). For in vivo experiments, 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, alternating with ad libitum diet, for a total of 6 weeks. At 8months of age, mice were evaluated in behavioral tests (open field, Y maze and elevated plus maze) and brains were dissected out to study neuronal and glial parameters. In vitro experiments were carried out in C6 astroglial and BV2 microglial cells lines. C6 cells were exposed to ABeta with and without nutrient restriction (FBS 2% vs FBS 10% in RPMI medium) and autophagy was evaluated. Conditioned media (CM) were used to stimulate BV2 microglia. Microglial NFkB nuclear translocation was increased when exposed to CM from C6 cells exposed to ABeta. This effect was prevented by serum restriction, suggesting that nutrient restriction is able to modulate the glial response to ABeta. Further work is needed to elucidate potential therapeutic effects of DR on experimental AD progression.