Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice

Dietary restriction (DR; reduced calorie intake) increases the lifespan of rodents and increases their resistance to cancer, diabetes and other age-re lated diseases. DR also exerts beneficial effects on the brain including en hanced learning and memory and increased resistance of neurons to excitotox ic, oxidative and metabolic insults. The mechanisms underlying the effects of DR on neuronal plasticity and survival are unknown, in the present study we show that levels of brain-derived neurotrophic factor (BDNF) are signif icantly increased in the hippocampus, cerebral cortex and striatum of mice maintained on an alternate day feeding DR regimen compared to animals fed a d libitum. Damage to hippocampal neurons induced by the excitotoxin kainic acid was significantly reduced in mice maintained on DR, and this neuroprot ective effect was attenuated by intraventricular administration of a BDNF-b locking antibody. Our findings show that simply reducing food intake result s in increased levels of BDNF in brain cells, and suggest that the resultin g activation of BDNF signaling pathways plays a key role in the neuroprotec tive effect of DR. These results bolster accumulating evidence that DR may be an effective approach for increasing the resistance of the brain to dama ge and enhancing brain neuronal plasticity.