Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults

Food restriction (FR) in rodents is known to extend life span, reduce the i ncidence of age-related tumors, and suppress oxidative damage to proteins, lipids, and DNA in several organ systems. Excitotoxicity and mitochondrial impairment are believed to play major roles in the neuronal degeneration an d death that occurs in the brains of patients suffering from both acute bra in insults such as stroke and seizures, and chronic neurodegenerative condi tions such as Alzheimer's, Parkinson's, and Huntington's diseases. We now r eport chat FR (alternate-day feeding regimen for 2-4 months) in adult rats results in resistance of hippocampal neurons to excitotoxin-induced degener ation, and of striatal neurons to degeneration induced by the mitochondrial toxins 3-nitropropionic acid and malonate. FR greatly increased the resist ance of rats to kainate-induced deficits in performance in water-maze learn ing and memory tasks, and to 3-nitropropionic acid-induced impairment of mo tor function. These findings suggest that FR not only extends life span, bu t increases resistance of the brain to insults that involve metabolic compr omise and excitotoxicity.