Adult-onset deficiency in growth hormone and insulin-like growth factor-I decreases survival of dentate granule neurons: Insights into the regulation of adult hippocampal neurogenesis

Authors

  • Robin J. Lichtenwalner,

    1. Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    Current affiliation:
    1. Department of Neurology, University of Michigan Medical Center, 4412 Kresge III, 200 Zina Pitcher Place, Ann Arbor, MI 48109-0585
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  • M. Elizabeth Forbes,

    1. Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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  • William E. Sonntag,

    1. Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    2. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    3. Roena Kulynych Center for Memory and Cognition Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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  • David R. Riddle

    Corresponding author
    1. Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    2. Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    3. Roena Kulynych Center for Memory and Cognition Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    • Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1010
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Abstract

Insulin-like growth factor-I (IGF-I), long thought to provide critical trophic support during development, also has emerged as a candidate for regulating ongoing neuronal production in adulthood. Whether and how IGF-I influences each phase of neurogenesis, however, remains unclear. In the current study, we used a selective model of growth hormone (GH) and plasma IGF-I deficiency to evaluate the role of GH and IGF-I in regulating cell proliferation, survival, and neuronal differentiation in the adult dentate gyrus. GH/IGF-I-deficient dwarf rats of the Lewis strain were made GH/IGF-I replete throughout development via twice daily injections of GH, and then GH/IGF-I deficiency was initiated in adulthood by removing animals from GH treatment. Bromodeoxyuridine (BrdU) labeling revealed no effect of GH/IGF-I deficiency on cell proliferation, but adult-onset depletion of GH and plasma IGF-I significantly reduced the survival of newly generated cells in the dentate gyrus. Colabeling for BrdU and markers of immature and mature neurons revealed a selective effect of GH/IGF-I deficiency on the survival of more mature new neurons. The number of BrdU-labeled cells expressing the immature neuronal marker TUC-4 did not differ between GH/IGF-I-deficient and -replete animals, but the number expressing only the marker of maturity NeuN was lower in depleted animals. Taken together, results from the present study suggest that, under conditions of short-term GH/IGF-I deficiency during adulthood, dentate granule cells continue to be produced, to commit to a neuronal fate, and to begin the process of neuronal maturation, whereas survival of the new neurons is impaired. © 2005 Wiley-Liss, Inc.

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