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
✍ Scribed by Robin J. Lichtenwalner; M. Elizabeth Forbes; William E. Sonntag; David R. Riddle
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 397 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
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.