Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury

Dietary restriction (DR) increases the lifespan of rodents and increases th eir resistance to several different age-related diseases including cancer a nd diabetes. Beneficial effects of DR on brain plasticity and neuronal vuln erability to injury have recently been reported, but the underlying mechani sms are unknown. We report that levels of brain-derived neurotrophic factor (BDNF) are significantly increased in the hippocampus, cerebral cortex, an d striatum of rats maintained on a DR regimen compared to animals fed ad li bitum (AL). Seizure-induced damage to hippocampal neurons was significantly reduced in rats maintained on DR, and this beneficial effect was attenuate d by intraventricular administration of a BDNF-blocking antibody. These fin dings provide the first evidence that diet can effect expression of a neuro trophic factor, demonstrate that BDNF signaling plays a central role in the neuroprotective effect of DR, and proffer DR as an approach for reducing n euronal damage in neurodegenerative disorders.