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Constitutive serotonin transporter reduction resembles maternal separation with regard to stress-related gene expression
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.ORCID iD: 0000-0002-2174-2068
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
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2019 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 10, no 7, p. 3132-3142Article in journal (Refereed) Published
Abstract [en]

Interactive effects between allelic variants of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) and stressors on depression symptoms have been documented, as well as questioned, by meta-analyses. Translational models of constitutive 5-htt reduction and experimentally controlled stressors often led to inconsistent behavioral and molecular findings and often did not include females. The present study sought to investigate the effect of 5-htt genotype, maternal separation, and sex on the expression of stress-related candidate genes in the rat hippocampus and frontal cortex. The mRNA expression levels of Avp, Pomc, Crh, Crhbp, Crhr1, Bdnf, Ntrk2, Maoa, Maob, and Comt were assessed in the hippocampus and frontal cortex of 5-htt± and 5-htt+/+ male and female adult rats exposed, or not, to daily maternal separation for 180 min during the first 2 postnatal weeks. Gene- and brain region-dependent, but sex-independent, interactions between 5-htt genotype and maternal separation were found. Gene expression levels were higher in 5-htt+/+ rats not exposed to maternal separation compared with the other experimental groups. Maternal separation and 5-htt+/− genotype did not yield additive effects on gene expression. Correlative relationships, mainly positive, were observed within, but not across, brain regions in all groups except in non-maternally separated 5-htt+/+ rats. Gene expression patterns in the hippocampus and frontal cortex of rats exposed to maternal separation resembled the ones observed in rats with reduced 5-htt expression regardless of sex. These results suggest that floor effects of 5-htt reduction and maternal separation might explain inconsistent findings in humans and rodents.

Place, publisher, year, edition, pages
2019. Vol. 10, no 7, p. 3132-3142
Keywords [en]
Frontal cortex, hippocampus, maternal separation, serotonin transporter, gene expression
National Category
Neurosciences Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-381818DOI: 10.1021/acschemneuro.8b00595ISI: 000476685400012PubMedID: 30614673OAI: oai:DiVA.org:uu-381818DiVA, id: diva2:1304849
Funder
Swedish Society of Medicine, SLS-411161Fredrik och Ingrid Thurings StiftelseLars Hierta Memorial FoundationSwedish Research Council, K2012-61X-22090-01-3Swedish Research Council, VR: 2015-00495EU, FP7, Seventh Framework Programme, INCA 600398Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceAvailable from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-09-20Bibliographically approved

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Comasco, ErikaSchijven, Dickde Maeyer, HanneVrettou, MariaNylander, IngridSundström-Poromaa, IngerOlivier, Jocelien D. A.

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Comasco, ErikaSchijven, Dickde Maeyer, HanneVrettou, MariaNylander, IngridSundström-Poromaa, IngerOlivier, Jocelien D. A.
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Science for Life Laboratory, SciLifeLabComasco: NeuropsychopharmacologyDepartment of Women's and Children's HealthDepartment of NeuroscienceDepartment of Pharmaceutical BiosciencesReproductive Health
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ACS Chemical Neuroscience
NeurosciencesBiochemistry and Molecular Biology

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