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| Adult hippocampal neurogenesis is modulated by stress and various antidepressants. Neuronal stem cells express high levels of telomerase in adult hippocampus. Here, we used 3'-azido-deoxythymidine (AZT), a nucleoside reverse transcriptase inhibitor, and constructed recombinant adenovirus vector expressing mouse telomerase reverse transcriptase (Ad-mTERT-GFP) to investigate whether hippocampal telomerase implicate in pathophysiology of depression by regulating hippocampal neurogenesis. We found that infusion of AZT into hippocampal DG resulted in a decrease of neurogenesis in the hippocampus without causing neuronal degeneration, whereas infusion of Ad-mTERT-GFP into hippocampal DG upregulated hippocampal neurogenesis. The mice infused with AZT exhibited depression-like behaviors whereas the mice infused with Ad-mTERT-GFP exhibited antidepression-like behaviors both about 4 weeks after infusion. In addition, chronic stress resulted in a decrease in mTERT content in the hippocampus, reversed by chronic fluoxetine treatment. Furthermore, mTERT content in the SVZ, another telomerase expressed place in the adult brain, was unaffected after chronic stress exposure and infusion of AZT into SVZ did not induce depression-like phenotype. These results suggest that hippocampal telomerase is involved in the modulation of depression-related behaviors, possibly by regulating adult hippocampal neurogenesis. |
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| Keywords:Depression; Telomerase; Neurogenesis |
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