Cargando…

Two models of inescapable stress increase tph2 mRNA expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus

Expression of TPH2, the rate-limiting enzyme for brain serotonin synthesis, is elevated in the dorsal raphe nucleus (DR) of depressed suicide victims. One hypothesis is that this increase in TPH2 expression is stress-induced. Here, we used an established animal model to address whether exposure to a...

Descripción completa

Detalles Bibliográficos
Autores principales: Donner, Nina C., Kubala, Kenneth H., Hassell Jr., James E., Lieb, Margaret W., Nguyen, Kadi T., Heinze, Jared D., Drugan, Robert C., Maier, Steven F., Lowry, Christopher A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842308/
https://www.ncbi.nlm.nih.gov/pubmed/29520369
http://dx.doi.org/10.1016/j.ynstr.2018.01.003
_version_ 1783304874794942464
author Donner, Nina C.
Kubala, Kenneth H.
Hassell Jr., James E.
Lieb, Margaret W.
Nguyen, Kadi T.
Heinze, Jared D.
Drugan, Robert C.
Maier, Steven F.
Lowry, Christopher A.
author_facet Donner, Nina C.
Kubala, Kenneth H.
Hassell Jr., James E.
Lieb, Margaret W.
Nguyen, Kadi T.
Heinze, Jared D.
Drugan, Robert C.
Maier, Steven F.
Lowry, Christopher A.
author_sort Donner, Nina C.
collection PubMed
description Expression of TPH2, the rate-limiting enzyme for brain serotonin synthesis, is elevated in the dorsal raphe nucleus (DR) of depressed suicide victims. One hypothesis is that this increase in TPH2 expression is stress-induced. Here, we used an established animal model to address whether exposure to an acute stressor, inescapable tail shock (IS), increases tph2 mRNA and Tph2 protein expression, and if IS sensitizes the DR to a subsequent, heterotypic stressor. In Experiment 1, we measured tph2 mRNA expression 4 h after IS or home cage (HC) control conditions in male rats, using in situ hybridization histochemistry. In Experiment 2, we measured Tph2 protein expression 12 h or 24 h after IS using western blot. In Experiment 3, we measured tph2 mRNA expression following IS on Day 1, and cold swim stress (10 min, 15 °C) on Day 2. Inescapable tail shock was sufficient to increase tph2 mRNA expression 4 h and 28 h later, selectively in the dorsomedial DR (caudal aspect of the dorsal DR, cDRD; an area just rostral to the caudal DR, DRC) and increased Tph2 protein expression in the DRD (rostral and caudal aspects of the dorsal DR combined) 24 h later. Cold swim increased tph2 mRNA expression in the dorsomedial DR (cDRD) 4 h later. These effects were associated with increased immobility during cold swim, elevated plasma corticosterone, and a proinflammatory plasma cytokine milieu (increased interleukin (IL)-6, decreased IL-10). Our data demonstrate that two models of inescapable stress, IS and cold swim, increase tph2 mRNA expression selectively in the anxiety-related dorsomedial DR (cDRD).
format Online
Article
Text
id pubmed-5842308
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-58423082018-03-08 Two models of inescapable stress increase tph2 mRNA expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus Donner, Nina C. Kubala, Kenneth H. Hassell Jr., James E. Lieb, Margaret W. Nguyen, Kadi T. Heinze, Jared D. Drugan, Robert C. Maier, Steven F. Lowry, Christopher A. Neurobiol Stress Original Research Article Expression of TPH2, the rate-limiting enzyme for brain serotonin synthesis, is elevated in the dorsal raphe nucleus (DR) of depressed suicide victims. One hypothesis is that this increase in TPH2 expression is stress-induced. Here, we used an established animal model to address whether exposure to an acute stressor, inescapable tail shock (IS), increases tph2 mRNA and Tph2 protein expression, and if IS sensitizes the DR to a subsequent, heterotypic stressor. In Experiment 1, we measured tph2 mRNA expression 4 h after IS or home cage (HC) control conditions in male rats, using in situ hybridization histochemistry. In Experiment 2, we measured Tph2 protein expression 12 h or 24 h after IS using western blot. In Experiment 3, we measured tph2 mRNA expression following IS on Day 1, and cold swim stress (10 min, 15 °C) on Day 2. Inescapable tail shock was sufficient to increase tph2 mRNA expression 4 h and 28 h later, selectively in the dorsomedial DR (caudal aspect of the dorsal DR, cDRD; an area just rostral to the caudal DR, DRC) and increased Tph2 protein expression in the DRD (rostral and caudal aspects of the dorsal DR combined) 24 h later. Cold swim increased tph2 mRNA expression in the dorsomedial DR (cDRD) 4 h later. These effects were associated with increased immobility during cold swim, elevated plasma corticosterone, and a proinflammatory plasma cytokine milieu (increased interleukin (IL)-6, decreased IL-10). Our data demonstrate that two models of inescapable stress, IS and cold swim, increase tph2 mRNA expression selectively in the anxiety-related dorsomedial DR (cDRD). Elsevier 2018-01-17 /pmc/articles/PMC5842308/ /pubmed/29520369 http://dx.doi.org/10.1016/j.ynstr.2018.01.003 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Research Article
Donner, Nina C.
Kubala, Kenneth H.
Hassell Jr., James E.
Lieb, Margaret W.
Nguyen, Kadi T.
Heinze, Jared D.
Drugan, Robert C.
Maier, Steven F.
Lowry, Christopher A.
Two models of inescapable stress increase tph2 mRNA expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus
title Two models of inescapable stress increase tph2 mRNA expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus
title_full Two models of inescapable stress increase tph2 mRNA expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus
title_fullStr Two models of inescapable stress increase tph2 mRNA expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus
title_full_unstemmed Two models of inescapable stress increase tph2 mRNA expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus
title_short Two models of inescapable stress increase tph2 mRNA expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus
title_sort two models of inescapable stress increase tph2 mrna expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842308/
https://www.ncbi.nlm.nih.gov/pubmed/29520369
http://dx.doi.org/10.1016/j.ynstr.2018.01.003
work_keys_str_mv AT donnerninac twomodelsofinescapablestressincreasetph2mrnaexpressionintheanxietyrelateddorsomedialpartofthedorsalraphenucleus
AT kubalakennethh twomodelsofinescapablestressincreasetph2mrnaexpressionintheanxietyrelateddorsomedialpartofthedorsalraphenucleus
AT hasselljrjamese twomodelsofinescapablestressincreasetph2mrnaexpressionintheanxietyrelateddorsomedialpartofthedorsalraphenucleus
AT liebmargaretw twomodelsofinescapablestressincreasetph2mrnaexpressionintheanxietyrelateddorsomedialpartofthedorsalraphenucleus
AT nguyenkadit twomodelsofinescapablestressincreasetph2mrnaexpressionintheanxietyrelateddorsomedialpartofthedorsalraphenucleus
AT heinzejaredd twomodelsofinescapablestressincreasetph2mrnaexpressionintheanxietyrelateddorsomedialpartofthedorsalraphenucleus
AT druganrobertc twomodelsofinescapablestressincreasetph2mrnaexpressionintheanxietyrelateddorsomedialpartofthedorsalraphenucleus
AT maierstevenf twomodelsofinescapablestressincreasetph2mrnaexpressionintheanxietyrelateddorsomedialpartofthedorsalraphenucleus
AT lowrychristophera twomodelsofinescapablestressincreasetph2mrnaexpressionintheanxietyrelateddorsomedialpartofthedorsalraphenucleus