Hippocampal telomerase is involved in the modulation of depressive behaviors
Open accessAbstract
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 (100 mg · 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 (0.7 μmol, 2 μl) 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.
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Preclinical studies suggest that hippocampal TA in mice is involved in the regulation of depression-like behaviors and possibly antidepressant-like mechanisms, perhaps by regulating adult neurogenesis in the dentate gyrus.
“These preclinical studies suggest that hippocampal TA in mice is involved in the regulation of “depression-like” behaviors and possibly “antidepressant-like” mechanisms, perhaps by regulating adult neurogenesis in the dentate gyrus (Zhou et al., 2011).”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Zhou et al., 2011
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References 60 · Cited by 105
- Authors
- Zhou, Q.-G., Hu, Y., Wu, D.-L., Zhu, L.-J., Chen, C., Jin, X., Luo, C.-X., Wu, H.-Y., Zhang, J., & Zhu, D.-Y.
- Affiliations
- Nanjing Medical University (CN)
- Corresponding author
- Zhu, Dong-Ya
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-08-24
- Volume
- 31
- Issue
- 34
- Pages
- 12258-12269
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6623221
- OpenAlex
- W1967985498
- Cited by
- 105
- References
- 60
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 8 · 2015: 15 · 2014: 5 · 2013: 6 · 2012: 2
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (973 Program, 81000586, 2011CB504400)
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province
- Nanjing Medical University
- National Key Research and Development Program of China (2011CB504400)
- Specialized Research Fund for the Doctoral Program of Higher Education of China
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- telomerase, telomerase reverse transcriptase, depression, chronic mild stress, hippocampus, adult neurogenesis, dentate gyrus, fluoxetine, zidovudine, antidepressant-like behavior, telomere shortening, mood disorders
- MeSH terms
- Aging, Animals, Behavior, Animal, Cells, Cultured, Depressive Disorder, Disease Models, Animal, Female, Hippocampus, Mice, Inbred C57BL, Stress, Psychological, Telomerase, Mice, Neurogenesis
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