Cargando…

Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice

Stressors activate the hypothalamic-pituitary-adrenal (HPA) axis and immune system eliciting changes in cognitive function, mood and anxiety. An important link between stress and altered behavior is stimulation of the Kynurenine Pathway which generates neuroactive and immunomodulatory kynurenines. T...

Descripción completa

Detalles Bibliográficos
Autores principales: Dostal, Carlos R., Carson Sulzer, Megan, Kelley, Keith W., Freund, Gregory G., McCusker, Robert H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840960/
https://www.ncbi.nlm.nih.gov/pubmed/29520368
http://dx.doi.org/10.1016/j.ynstr.2017.02.002
_version_ 1783304673967472640
author Dostal, Carlos R.
Carson Sulzer, Megan
Kelley, Keith W.
Freund, Gregory G.
McCusker, Robert H.
author_facet Dostal, Carlos R.
Carson Sulzer, Megan
Kelley, Keith W.
Freund, Gregory G.
McCusker, Robert H.
author_sort Dostal, Carlos R.
collection PubMed
description Stressors activate the hypothalamic-pituitary-adrenal (HPA) axis and immune system eliciting changes in cognitive function, mood and anxiety. An important link between stress and altered behavior is stimulation of the Kynurenine Pathway which generates neuroactive and immunomodulatory kynurenines. Tryptophan entry into this pathway is controlled by rate-limiting indoleamine/tryptophan 2,3-dioxygenases (DOs: Ido1, Ido2, Tdo2). Although implicated as mediating changes in behavior, detecting stress-induced DO expression has proven inconsistent. Thus, C57BL/6J mice were used to characterize DO expression in brain-regions, astrocytes and microglia to characterize restraint-stress-induced DO expression. Stress increased kynurenine in brain and plasma, demonstrating increased DO activity. Of three Ido1 transcripts, only Ido1-v1 expression was increased by stress and within astrocytes, not microglia, indicating transcript- and glial-specificity. Stress increased Ido1-v1 only in frontal cortex and hypothalamus, indicating brain-region specificity. Of eight Ido2 transcripts, Ido2-v3 expression was increased by stress, again only within astrocytes. Likewise, stress increased Tdo2-FL expression in astrocytes, not microglia. Interestingly, Ido2 and Tdo2 transcripts were not correspondingly induced in Ido1-knockout (Ido1(KO)) mice, suggesting that Ido1 is necessary for the central DO response to acute stress. Unlike acute inflammatory models resulting in DO induction within microglia, only astrocyte DO expression was increased by acute restraint-stress, defining their unique role during stress-dependent activation of the Kynurenine Pathway.
format Online
Article
Text
id pubmed-5840960
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-58409602018-03-08 Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice Dostal, Carlos R. Carson Sulzer, Megan Kelley, Keith W. Freund, Gregory G. McCusker, Robert H. Neurobiol Stress Original Research Article Stressors activate the hypothalamic-pituitary-adrenal (HPA) axis and immune system eliciting changes in cognitive function, mood and anxiety. An important link between stress and altered behavior is stimulation of the Kynurenine Pathway which generates neuroactive and immunomodulatory kynurenines. Tryptophan entry into this pathway is controlled by rate-limiting indoleamine/tryptophan 2,3-dioxygenases (DOs: Ido1, Ido2, Tdo2). Although implicated as mediating changes in behavior, detecting stress-induced DO expression has proven inconsistent. Thus, C57BL/6J mice were used to characterize DO expression in brain-regions, astrocytes and microglia to characterize restraint-stress-induced DO expression. Stress increased kynurenine in brain and plasma, demonstrating increased DO activity. Of three Ido1 transcripts, only Ido1-v1 expression was increased by stress and within astrocytes, not microglia, indicating transcript- and glial-specificity. Stress increased Ido1-v1 only in frontal cortex and hypothalamus, indicating brain-region specificity. Of eight Ido2 transcripts, Ido2-v3 expression was increased by stress, again only within astrocytes. Likewise, stress increased Tdo2-FL expression in astrocytes, not microglia. Interestingly, Ido2 and Tdo2 transcripts were not correspondingly induced in Ido1-knockout (Ido1(KO)) mice, suggesting that Ido1 is necessary for the central DO response to acute stress. Unlike acute inflammatory models resulting in DO induction within microglia, only astrocyte DO expression was increased by acute restraint-stress, defining their unique role during stress-dependent activation of the Kynurenine Pathway. Elsevier 2017-02-12 /pmc/articles/PMC5840960/ /pubmed/29520368 http://dx.doi.org/10.1016/j.ynstr.2017.02.002 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research Article
Dostal, Carlos R.
Carson Sulzer, Megan
Kelley, Keith W.
Freund, Gregory G.
McCusker, Robert H.
Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice
title Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice
title_full Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice
title_fullStr Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice
title_full_unstemmed Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice
title_short Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice
title_sort glial and tissue-specific regulation of kynurenine pathway dioxygenases by acute stress of mice
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840960/
https://www.ncbi.nlm.nih.gov/pubmed/29520368
http://dx.doi.org/10.1016/j.ynstr.2017.02.002
work_keys_str_mv AT dostalcarlosr glialandtissuespecificregulationofkynureninepathwaydioxygenasesbyacutestressofmice
AT carsonsulzermegan glialandtissuespecificregulationofkynureninepathwaydioxygenasesbyacutestressofmice
AT kelleykeithw glialandtissuespecificregulationofkynureninepathwaydioxygenasesbyacutestressofmice
AT freundgregoryg glialandtissuespecificregulationofkynureninepathwaydioxygenasesbyacutestressofmice
AT mccuskerroberth glialandtissuespecificregulationofkynureninepathwaydioxygenasesbyacutestressofmice