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Submitted on August 23, 2004
Accepted on November 15, 2004
Geriatrics Research, Department of Internal Medicine, Department of Physiology and Department of Neurology, Southern Illinois University School of Medicine, Springfield, IL 62794; Laboratory of Genetics, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037
* To whom correspondence should be addressed. E-mail: abartke{at}siumed.edu.
Neurogenesis occurs throughout adult life in dentate gyrus of mammalian hippocampus and has been suggested to play an important role in cognitive function. Multiple trophic factors including IGF-I have been demonstrated to regulate hippocampal neurogenesis. Ames dwarf mice live considerably longer than normal animals, and maintain physiological function at youthful levels, including cognitive function, despite deficiency of circulating GH and IGF-I. Here we show an increase in numbers of newly generated cells (BrdU positive) and new born neurons (NeuN and BrdU positive) in the dentate gyrus of adult dwarf mice compared with normal mice using bromodeoxyuridine labeling. In spite of the profound suppression of hippocampal GH expression, hippocampal IGF-I protein levels are upregulated and the corresponding mRNAs are as high in Ames dwarf as in normal mice. Our results suggest that local/hippocampal IGF-I expression may have induced the increase in hippocampal neurogenesis and increased neurogenesis might contribute to the maintenance of youthful levels of cognitive function during aging in these long-lived animals.
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