Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Enduring effects of conditional brain serotonin knockdown, followed by recovery, on adult rat neurogenesis and behavior

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB

Item Type:Article
Title:Enduring effects of conditional brain serotonin knockdown, followed by recovery, on adult rat neurogenesis and behavior
Creators Name:Sidorova, M., Kronenberg, G., Matthes, S., Petermann, M., Hellweg, R., Tuchina, O., Bader, M., 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

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library