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:	Maria Sidorova, Golo Kronenberg, Susann Matthes, Markus Petermann, Rainer Hellweg, Oksana Tuchina, Michael Bader, Natalia Alenina, Friederike Klempin
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	serotonin <i>Tph2</i> depression neurogenesis stem cells BrdU Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a730e1ad826f4c2a8a0a2aff5ece89da
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spelling	oai:doaj.org-article:a730e1ad826f4c2a8a0a2aff5ece89da2021-11-25T17:13:15ZEnduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior10.3390/cells101132402073-4409https://doaj.org/article/a730e1ad826f4c2a8a0a2aff5ece89da2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3240https://doaj.org/toc/2073-4409Serotonin (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 (<i>Tph2</i>) 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 <i>Tph2</i> 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.Maria SidorovaGolo KronenbergSusann MatthesMarkus PetermannRainer HellwegOksana TuchinaMichael BaderNatalia AleninaFriederike KlempinMDPI AGarticleserotonin<i>Tph2</i>depressionneurogenesisstem cellsBrdUBiology (General)QH301-705.5ENCells, Vol 10, Iss 3240, p 3240 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	serotonin <i>Tph2</i> depression neurogenesis stem cells BrdU Biology (General) QH301-705.5
spellingShingle	serotonin <i>Tph2</i> depression neurogenesis stem cells BrdU Biology (General) QH301-705.5 Maria Sidorova Golo Kronenberg Susann Matthes Markus Petermann Rainer Hellweg Oksana Tuchina Michael Bader Natalia Alenina Friederike Klempin Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior
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 (<i>Tph2</i>) 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 <i>Tph2</i> 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.
format	article
author	Maria Sidorova Golo Kronenberg Susann Matthes Markus Petermann Rainer Hellweg Oksana Tuchina Michael Bader Natalia Alenina Friederike Klempin
author_facet	Maria Sidorova Golo Kronenberg Susann Matthes Markus Petermann Rainer Hellweg Oksana Tuchina Michael Bader Natalia Alenina Friederike Klempin
author_sort	Maria Sidorova
title	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_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_sort	enduring effects of conditional brain serotonin knockdown, followed by recovery, on adult rat neurogenesis and behavior
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a730e1ad826f4c2a8a0a2aff5ece89da
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Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior

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