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Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior

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-e...

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Autores principales: Sidorova, Maria, Kronenberg, Golo, Matthes, Susann, Petermann, Markus, Hellweg, Rainer, Tuchina, Oksana, Bader, Michael, Alenina, Natalia, Klempin, Friederike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618971/
https://www.ncbi.nlm.nih.gov/pubmed/34831469
http://dx.doi.org/10.3390/cells10113240
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author Sidorova, Maria
Kronenberg, Golo
Matthes, Susann
Petermann, Markus
Hellweg, Rainer
Tuchina, Oksana
Bader, Michael
Alenina, Natalia
Klempin, Friederike
author_facet Sidorova, Maria
Kronenberg, Golo
Matthes, Susann
Petermann, Markus
Hellweg, Rainer
Tuchina, Oksana
Bader, Michael
Alenina, Natalia
Klempin, Friederike
author_sort Sidorova, Maria
collection PubMed
description 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.
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spelling pubmed-86189712021-11-27 Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior Sidorova, Maria Kronenberg, Golo Matthes, Susann Petermann, Markus Hellweg, Rainer Tuchina, Oksana Bader, Michael Alenina, Natalia Klempin, Friederike Cells Brief Report 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. MDPI 2021-11-19 /pmc/articles/PMC8618971/ /pubmed/34831469 http://dx.doi.org/10.3390/cells10113240 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Sidorova, Maria
Kronenberg, Golo
Matthes, Susann
Petermann, Markus
Hellweg, Rainer
Tuchina, Oksana
Bader, Michael
Alenina, Natalia
Klempin, Friederike
Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior
title Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior
title_full Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior
title_fullStr Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior
title_full_unstemmed Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior
title_short Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior
title_sort enduring effects of conditional brain serotonin knockdown, followed by recovery, on adult rat neurogenesis and behavior
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618971/
https://www.ncbi.nlm.nih.gov/pubmed/34831469
http://dx.doi.org/10.3390/cells10113240
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