Article

Journal of Molecular Neuroscience

, Volume 16, Issue 1, pp 1-12

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

  • Wenzhen DuanAffiliated withLaboratory of Neuroscience, National Institute on Aging Gerontology Research Center
  • , JaeWon LeeAffiliated withLaboratory of Neuroscience, National Institute on Aging Gerontology Research CenterSanders-Brown Research Center on Aging and Department of Anatomy & Neurobiology, University of Kentucky
  • , ZhiHong GuoAffiliated withLaboratory of Neuroscience, National Institute on Aging Gerontology Research Center
  • , Mark P. MattsonAffiliated withLaboratory of Neuroscience, National Institute on Aging Gerontology Research CenterSanders-Brown Research Center on Aging and Department of Anatomy & Neurobiology, University of KentuckyDepartment of Neuroscience, Johns Hopkins University School of Medicine

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Abstract

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

Index Entries

Apoptosis BDNF caloric restriction cerebral cortex epileptic seizures glutamate