Growth hormone signaling and hippocampal neurogenesis: Insights from genetic models

✍ Scribed by Mark I. Ransome; Ann M. Turnley

• Book ID: 102852740
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 781 KB
• Volume: 18
• Category: Article
• ISSN: 1050-9631
• DOI: 10.1002/hipo.20463

✦ Synopsis

Abstract

Adult hippocampal neurogenesis (AHN) is modulated by a variety of factors through effects on the proliferation‐differentiation‐survival regulatory axis. We have employed growth hormone receptor knockout (GH‐R−/−) and suppressor of cytokine signaling‐2 transgenic (SOCS‐2 Tg) mice as models of altered GH‐signaling to assess their affects on basal and exercised‐induced hippocampal neurogenesis. Assessment of proliferation 24‐h after 7‐days of bromodeoxyuridine (BrdU) labeling with or without voluntary running showed that the density of BrdU(+) cells in the subgranular zone remained unchanged between genotypes in control housing, while running induced significant increases in BrdU‐labeled cells in WT, GH‐R−/−, and SOCS‐2 Tg mice. The proportion of BrdU/doublecortin and BrdU/S100β cells did not vary between genotype or running conditions at this time‐point. Assessment of cell survival 28‐days after BrdU labeling showed that SOCS‐2 Tg animals had significantly higher BrdU(+) cell densities in the granule cell layer compared to WT and GH‐R−/− animals in control housing and after voluntary running. There were no differences in cell survival between WT and GH‐R−/− mice with or without running. Mature phenotype analysis showed similar proportions of BrdU/NeuN and BrdU/S100β in all groups. While SOCS‐2 Tg mice had similar social interaction behaviors and sensorimotor gating, they appeared to be less anxious with heightened basal locomotor activity and showed enhanced performance in the Morris watermaze test. Overall, our data indicated that mice over‐expressing SOCS‐2 showed increased survival of neurons generated during AHN, which correlated with improved performance in a hippocampal‐dependent cognitive task. Furthermore, voluntary running increased AHN in WT, SOCS‐2 Tg, and serum‐IGF‐1‐deficient GH‐R−/− mice. © 2008 Wiley‐Liss, Inc.