Effects of maternal separation on serotonergic systems in the dorsal and median raphe nuclei of adult male Tph2-deficient mice.

Szczegóły
Abstrakt

Tytuł:: Effects of maternal separation on serotonergic systems in the dorsal and median raphe nuclei of adult male Tph2-deficient mice.
Autorzy:: Lieb MW; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: .
Weidner M; Division of Molecular Psychiatry, Center of Mental Health, University of Wuerzburg, Wuerzburg, Germany; Department of Psychiatry and Psychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands. Electronic address: Weidner_.
Arnold MR; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: .
Loupy KM; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: .
Nguyen KT; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: .
Hassell JE Jr; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: .
Schnabel KS; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: .
Kern R; Division of Molecular Psychiatry, Center of Mental Health, University of Wuerzburg, Wuerzburg, Germany. Electronic address: .
Day HEW; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: .
Lesch KP; Division of Molecular Psychiatry, Center of Mental Health, University of Wuerzburg, Wuerzburg, Germany; Department of Psychiatry and Psychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. Electronic address: .
Waider J; Division of Molecular Psychiatry, Center of Mental Health, University of Wuerzburg, Wuerzburg, Germany. Electronic address: Waider_.
Lowry CA; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA; Department of Physical Medicine & Rehabilitation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Veterans Health Administration, Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Rocky Mountain Regional Veterans Affairs Medical Center (RMRVAMC), Aurora, CO 80045, USA; Military and Veteran Microbiome Consortium for Research and Education (MVM-CoRE), Aurora, CO 80045, USA. Electronic address: .
Źródło:: Behavioural brain research [Behav Brain Res] 2019 Nov 05; Vol. 373, pp. 112086. Date of Electronic Publication: 2019 Jul 15.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
Język:: English
Imprint Name(s):: Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
MeSH Terms:: Raphe Nuclei/*physiopathology
Stress, Psychological/*metabolism
Tryptophan Hydroxylase/*metabolism
Animals ; Corticosterone/metabolism ; Dorsal Raphe Nucleus/drug effects ; Female ; Male ; Maternal Deprivation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Organic Cation Transport Proteins/metabolism ; Raphe Nuclei/drug effects ; Receptor, Serotonin, 5-HT1A/metabolism ; Receptors, Corticotropin-Releasing Hormone/metabolism ; Serotonergic Neurons/metabolism ; Serotonin/metabolism ; Serotonin Plasma Membrane Transport Proteins/genetics ; Tryptophan Hydroxylase/genetics ; Tryptophan Hydroxylase/physiology
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Grant Information:: I21 RX002232 United States RX RRD VA; R01 MH086539 United States MH NIMH NIH HHS; R21 MH116263 United States MH NIMH NIH HHS; 1R21MH116263 United States MH NIMH NIH HHS
Contributed Indexing:: Keywords: Crhr2; Gene expression; Htr1a; Maternal separation; Slc22a3; Slc6a4
Substance Nomenclature:: 0 (Htr1a protein, mouse)
0 (Organic Cation Transport Proteins)
0 (Receptors, Corticotropin-Releasing Hormone)
0 (Serotonin Plasma Membrane Transport Proteins)
0 (solute carrier family 22 (organic cation transporter), member 3)
112692-38-3 (Receptor, Serotonin, 5-HT1A)
333DO1RDJY (Serotonin)
EC 1.14.16.4 (Tph2 protein, mouse)
EC 1.14.16.4 (Tryptophan Hydroxylase)
W980KJ009P (Corticosterone)
Entry Date(s):: Date Created: 20190719 Date Completed: 20200914 Latest Revision: 20201106
Update Code:: 20240105
PubMed Central ID:: PMC6774352
DOI:: 10.1016/j.bbr.2019.112086
PMID:: 31319134
: Czasopismo naukowe

Previous studies have highlighted interactions between serotonergic systems and adverse early life experience as important gene x environment determinants of risk of stress-related psychiatric disorders. Evidence suggests that mice deficient in Tph2, the rate-limiting enzyme for brain serotonin synthesis, display disruptions in behavioral phenotypes relevant to stress-related psychiatric disorders. The aim of this study was to determine how maternal separation in wild-type, heterozygous, and Tph2 knockout mice affects mRNA expression of serotonin-related genes. Serotonergic genes studied included Tph2, the high-affinity, low-capacity, sodium-dependent serotonin transporter (Slc6a4), the serotonin type 1a receptor (Htr1a), and the corticosterone-sensitive, low-affinity, high-capacity sodium-independent serotonin transporter, organic cation transporter 3 (Slc22a3). Furthermore, we studied corticotropin-releasing hormone receptors 1 (Crhr1) and 2 (Crhr2), which play important roles in controlling serotonergic neuronal activity. For this study, offspring of Tph2 heterozygous dams were exposed to daily maternal separation for the first two weeks of life. Adult, male wild-type, heterozygous, and homozygous offspring were subsequently used for molecular analysis. Maternal separation differentially altered serotonergic gene expression in a genotype- and topographically-specific manner. For example, maternal separation increased Slc6a4 mRNA expression in the dorsal part of the dorsal raphe nucleus in Tph2 heterozygous mice, but not in wild-type or knockout mice. Overall, these data are consistent with the hypothesis that gene x environment interactions, including serotonergic genes and adverse early life experience, play an important role in vulnerability to stress-related psychiatric disorders.
(Copyright © 2019 Elsevier B.V. All rights reserved.)

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