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

Ann Neurol. 1999 Jan;45(1):8-15.


Food restriction (FR) in rodents is known to extend life span, reduce the incidence 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 and death that occurs in the brains of patients suffering from both acute brain insults such as stroke and seizures, and chronic neurodegenerative conditions such as Alzheimer's, Parkinson's, and Huntington's diseases. We now report that FR (alternate-day feeding regimen for 2-4 months) in adult rats results in resistance of hippocampal neurons to excitotoxin-induced degeneration, and of striatal neurons to degeneration induced by the mitochondrial toxins 3-nitropropionic acid and malonate. FR greatly increased the resistance of rats to kainate-induced deficits in performance in water-maze learning and memory tasks, and to 3-nitropropionic acid-induced impairment of motor function. These findings suggest that FR not only extends life span, but increases resistance of the brain to insults that involve metabolic compromise and excitotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antihypertensive Agents
  • Behavior, Animal / physiology
  • Brain Diseases / chemically induced
  • Brain Diseases / metabolism*
  • Corpus Striatum / physiology
  • Diet
  • Energy Intake*
  • Excitatory Amino Acid Agonists
  • Hippocampus / metabolism
  • Kainic Acid
  • Male
  • Malonates
  • Maze Learning / physiology
  • Memory / physiology
  • Mitochondria / metabolism
  • Neurotoxins / metabolism*
  • Nitro Compounds
  • Oxidative Stress / physiology
  • Propionates
  • Rats
  • Rats, Sprague-Dawley
  • Visual Cortex / physiology


  • Antihypertensive Agents
  • Excitatory Amino Acid Agonists
  • Malonates
  • Neurotoxins
  • Nitro Compounds
  • Propionates
  • malonic acid
  • 3-nitropropionic acid
  • Kainic Acid