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| Item Type: | Article |
|---|---|
| Title: | Enduring effects of conditional brain serotonin knockdown, followed by recovery, on adult rat neurogenesis and behavior |
| Creators Name: | Sidorova, M. and Kronenberg, G. and Matthes, S. and Petermann, M. and Hellweg, R. and Tuchina, O. and Bader, M. and Alenina, N. and Klempin, F. |
| Abstract: | Serotonin (5-hydroxytryptamine, 5-HT) is a crucial signal in the neurogenic niche of the hippocampus, where it is involved in antidepressant action. Here, we utilized a new transgenic rat model (TetO-shTPH2), where brain 5-HT levels can be acutely altered based on doxycycline (Dox)-inducible shRNA-expression. On/off stimulations of 5-HT concentrations might uniquely mirror the clinical course of major depression (e.g., relapse after discontinuation of antidepressants) in humans. Specifically, we measured 5-HT levels, and 5-HT metabolite 5-HIAA, in various brain areas following acute tryptophan hydroxylase 2 (Tph2) knockdown, and replenishment, and examined behavior and proliferation and survival of newly generated cells in the dentate gyrus. We found that decreased 5-HT levels in the prefrontal cortex and raphe nuclei, but not in the hippocampus of TetO-shTPH2 rats, lead to an enduring anxious phenotype. Surprisingly, the reduction in 5-HT synthesis is associated with increased numbers of BrdU-labeled cells in the dentate gyrus. At 3 weeks of Tph2 replenishment, 5-HT levels return to baseline and survival of newly generated cells is unaffected. We speculate that the acutely induced decrease in 5-HT concentrations and increased neurogenesis might represent a compensatory mechanism. |
| Keywords: | Serotonin, Tph2, Depression, Neurogenesis, Stem Cells, BrdU, Behavior, Animals, Rats |
| Source: | Cells |
| ISSN: | 2073-4409 |
| Publisher: | MDPI |
| Volume: | 10 |
| Number: | 11 |
| Page Range: | 3240 |
| Date: | 19 November 2021 |
| Official Publication: | https://doi.org/10.3390/cells10113240 |
| PubMed: | View item in PubMed |
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