Effects of maternal separation on serotonergic systems in the dorsal and median raphe nuclei of adult male Tph2-deficient mice.
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
Stress, Psychological
/ metabolism
Tryptophan Hydroxylase
/ genetics
Crhr2
Gene expression
Htr1a
Maternal separation
Slc22a3
Slc6a4
Journal
Behavioural brain research
ISSN: 1872-7549
Titre abrégé: Behav Brain Res
Pays: Netherlands
ID NLM: 8004872
Informations de publication
Date de publication:
05 11 2019
05 11 2019
Historique:
received:
03
02
2019
revised:
18
06
2019
accepted:
13
07
2019
pubmed:
19
7
2019
medline:
15
9
2020
entrez:
19
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31319134
pii: S0166-4328(19)30198-6
doi: 10.1016/j.bbr.2019.112086
pmc: PMC6774352
mid: NIHMS1536309
pii:
doi:
Substances chimiques
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
0
Receptor, Serotonin, 5-HT1A
112692-38-3
Serotonin
333DO1RDJY
Tph2 protein, mouse
EC 1.14.16.4
Tryptophan Hydroxylase
EC 1.14.16.4
Corticosterone
W980KJ009P
Types de publication
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.
Langues
eng
Sous-ensembles de citation
IM
Pagination
112086Subventions
Organisme : RRD VA
ID : I21 RX002232
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH086539
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH116263
Pays : United States
Organisme : NIMH NIH HHS
ID : 1R21MH116263
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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