Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats
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The adult brain contains neural stem cells that are capable of proliferating, differentiating into neurons or glia, and then either surviving or dying. This process of neural-cell production (neurogenesis) in the dentate gyrus of the hippocampus is responsive to brain injury, and both mental and physical activity. We now report that neurogenesis in the dentate gyrus can also be modified by diet. Previous studies have shown that dietary restriction (DR) can suppress agerelated deficits in learning and memory, and can increase resistance of neurons to degeneration in experimental models of neurodegenerative disorders. We found that maintenance of adult rats on a DR regimen results in a significant increase in the numbers of newly produced neural cells in the dentate gyrus of the hippocampus, as determined by stereologic analysis of cells labeled with the DNA precursor analog bromodeoxyuridine. The increase in neurogenesis in rats maintained on DR appears to result from decreased death of newly produced cells, rather than from increased cell proliferation. We further show that the expression of brain-derived neurotrophic factor, a trophic factor recently associated with neurogenesis, is increased in hippocampal cells of rats maintained on DR. Our data are the first evidence that diet can affect the process of neurogenesis, as well as the first evidence that diet can affect neurotrophic factor production. These findings provide insight into the mechanisms whereby diet impacts on brain plasticity, aging and neurodegenerative disorders.
Index EntriesAging Alzheimer’s disease bromodeoxyuridine caloric restriction hippocampus stem cells stereology
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- Gundersen H. J. G. and Jensen E. B. (1987) The efficiency of systematic sampling in stereology and its prediction. J. Micros. 147, 229–263.Google Scholar
- Lindvall O., Ernfors P., Bengzon J., Kokaia Z., Smith M. L., Siesjo B. K., and Persson H. (1992) Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma. Proc. Natl. Acad. Sci. USA 89, 648–652.PubMedCrossRefGoogle Scholar
- Mattson M. P., Lovell M. A., Furukawa K., and Markesbery W. R. (1995) Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular Ca2+ concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. J. Neurochem. 65, 1740–1751.PubMedCrossRefGoogle Scholar
- Mattson M. P. (2000) Impact of dietary restriction on brain aging and neurodegenerative disorders: emerging findings from experimental and epidemiological studies. Anti-Aging Med. 2, 331–336.Google Scholar
- Mayeux R., Costa R., Bell K., Merchant C., Tung M. X., and Jacobs D. (1999) Reduced risk of Alzheimer’s disease among individuals with low calorie intake. Neurology 59, S296-S297.Google Scholar
- Seroogy K. B. and Herman J. P. (1997) In situ hybridization approaches to the study of the nervous system, in Neurochemistry: A Practical Approach, 2nd ed., Turner A. J. and Bachelard H. S., eds, Oxford University Press, Oxford, pp. 121–150.Google Scholar
- Weindruch R and Walford R. L. (1988) The Retardation of Aging and Disease by Dietary Restriction. Charles C. Thomas, Springfield, IL, p. 436.Google Scholar