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- Title
Hippocampal Telomerase Is Involved in the Modulation of Depressive Behaviors.
- Authors
Qi-Gang Zhou; Yao Hu; Dan-Lian Wu; Li-Juan Zhu; Chen Chen; Xing Jin; Chun-Xia Luo; Hai-Yin Wu; Jing Zhang; Dong-Ya Zhu
- Abstract
Telomere and telomerase alterations have been reported in mood disorders. However, the role of telomerase in depression remains unclear. Here we show that chronic mild stress (CMS) led to a significant decrease in telomerase reverse transcriptase (TERT) level and telomerase activity in the hippocampus. Treatment with antidepressant fluoxetine reversed the CMS-induced TERT and telomerase activity changes. Inhibiting telomerase by systemic administration (100mg · kg-1 · d-1, i.p., for 14 d), intrahippocampal microinjection (0.7 μmol, 2 μl), or infusion (using an osmotic minipump, 0.134 μg/μl, 0.25 μl/h) of 3′-azido-deoxythymidine (AZT) resulted in depression-like behaviors and impaired hippocampal neurogenesis in mice. In contrast, overexpressing telomerase by intrahippocampal infusion of recombinant adenovirus vector expressing mouse TERT (Ad-mTERT-GFP) led to neurogenesis upregulation, produced antidepressant-like behaviors, and prevented the CMS-induced behavioral modifications. Disrupting neurogenesis in the dentate gyrus by X-irradiation (15 Gy) of a restricted region of mouse brain containing the hippocampus abolished the antidepressant-like effect of Ad-mTERT-GFP. Additionally, AZT had no effect on DNA polymerase activity and did not cause cell damage in vitro and in vivo. Microinjection of AZT into the subventricular zone of lateral ventricle (0.7μmol, 2μl) inhibited local neurogenesis but had no behavioral effect. These results suggest that hippocampal telomerase is involved in the modulation of depression-related behaviors, possibly by regulating adult neurogenesis.
- Subjects
THERAPEUTICS; MENTAL depression; TELOMERASE; HIPPOCAMPUS (Brain); LABORATORY mice; DEVELOPMENTAL neurobiology; DNA polymerases; GENE expression; ANTIDEPRESSANTS
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 34, p12258
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0805-11.2011