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Folate deficiency inhibits proliferation of adult hippocampal progenitors

Kruman, Inna I.1 CA; Mouton, Peter R.2; Emokpae, Roland Jr3; Cutler, Roy G.3; Mattson, Mark P.3 4

Neuropharmacology and Neurotoxicology

Neurogenesis in the adult hippocampus may play important roles in learning and memory, and in recovery from injury. As recent findings suggest, the perturbance of homocysteine/folate or one-carbon metabolism can adversely affect both the developing and the adult brain, and increase the risk of neural tube defects and Alzheimer's disease. We report that dietary folic acid deficiency dramatically increased blood homocysteine levels and significantly reduced the number of proliferating cells in the dentate gyrus of the hippocampus in adult mice. In vitro, the perturbance of one-carbon metabolism repressed proliferation of cultured embryonic multipotent neuroepithelial progenitor cells and affected cell cycle distribution. Our results suggest that dietary folate deficiency inhibits proliferation of neuronal progenitor cells in the adult brain and thereby affects neurogenesis.

1Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351

2Laboratory of Experimental Gerontology

3Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224

4Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA

CACorresponding Author: inna.kruman@sunhealth.org

Received 20 April 2005; accepted 28 April 2005

© 2005 Lippincott Williams & Wilkins, Inc.