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Increased Neurogenesis in Dentate Gyrus of Long-Lived Ames Dwarf Mice

Geriatrics Research (L.Y.S., J.P., A.B.), Department of Internal Medicine (L.Y.S., J.P., A.B.), Department of Physiology (L.Y.S., A.B.), and Department of Neurology (S.E.), Southern Illinois University School of Medicine, Springfield, Illinois 62794; and Laboratory of Genetics (J.H.), The Salk Institute, La Jolla, California 92037

Address all correspondence and requests for reprints to: Dr. Andrzej Bartke, Southern Illinois University, School of Medicine, Department of Internal Medicine-Geriatrics Research, Room 4389, 801 North Rutledge, Springfield, Illinois 62794-9628. E-mail: abartke{at}siumed.edu.

Neurogenesis occurs throughout adult life in the 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 a deficiency of circulating GH and IGF-I. Here we show an increase in numbers of newly generated cells [bromodeoxyuridine (BrdU) positive] and newborn neurons (neuronal nuclear antigen and BrdU positive) in the dentate gyrus of adult dwarf mice compared with normal mice using BrdU labeling. Despite the profound suppression of hippocampal GH expression, hippocampal IGF-I protein levels are up-regulated 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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