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.
MeSH terms
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Actins / antagonists & inhibitors
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Animals
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Antibodies / pharmacology
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Brain / drug effects
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Brain / metabolism*
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Brain-Derived Neurotrophic Factor / antagonists & inhibitors
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Brain-Derived Neurotrophic Factor / biosynthesis*
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Brain-Derived Neurotrophic Factor / genetics
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Cell Survival / physiology*
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Epilepsy / chemically induced
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Epilepsy / drug therapy
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Epilepsy / metabolism
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Food Deprivation / physiology*
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Glutamic Acid / pharmacology
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Hippocampus / drug effects
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Hippocampus / metabolism
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Hippocampus / physiopathology
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Immunohistochemistry
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Kainic Acid / pharmacology
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Male
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Neostriatum / drug effects
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Neostriatum / metabolism
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Nerve Growth Factor / biosynthesis
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Nerve Growth Factor / genetics
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Neurons / drug effects
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Neurons / metabolism*
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Neuroprotective Agents / metabolism*
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Neurotoxins / metabolism*
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
Substances
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Actins
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Antibodies
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Brain-Derived Neurotrophic Factor
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Neuroprotective Agents
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Neurotoxins
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RNA, Messenger
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Glutamic Acid
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Nerve Growth Factor
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Kainic Acid