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Effects of repeated adolescent stress and serotonin transporter gene partial knockout in mice on behaviors and brain structures relevant to major depression

Please always quote using this URN: urn:nbn:de:bvb:20-opus-122240
  • In humans, exposure to stress during development is associated with structural and functional alterations of the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HC) and their circuits of connectivity, and with an increased risk for developing major depressive disorder particularly in carriers of the short (s) variant of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR). Although changes in these regions are found in carriers of the s allele and/or in depressed patients, evidence for a specific genotype xIn humans, exposure to stress during development is associated with structural and functional alterations of the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HC) and their circuits of connectivity, and with an increased risk for developing major depressive disorder particularly in carriers of the short (s) variant of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR). Although changes in these regions are found in carriers of the s allele and/or in depressed patients, evidence for a specific genotype x developmental stress effect on brain structure and function is limited. Here, we investigated the effect of repeated stress exposure during adolescence in mice with partial knockout of the 5-HIT gene (HET) vs. wildtype (WT) on early-adulthood behavioral measures and brain structure [using magnetic resonance imaging (MRI)] relevant to human major depression. Behaviorally, adolescent stress (AS) increased anxiety and decreased activity and did so to a similar degree in HET and WT. In a probabilistic reversal learning task, HET-AS mice achieved fewer reversals than did HET-No-AS mice. 5-HIT genotype and AS were without effect on corticosterone stress response. In terms of structural brain differences, AS reduced the volume of two long-range white matter tracts, the optic tract (OT) and the cerebral peduncle (CP), in WT mice specifically. In a region-of-interest analysis, AS was associated with increased HC volume and HET genotype with a decreased frontal lobe volume. In conclusion, we found that 5-HIT and AS genotype exerted long-term effects on behavior and development of brain regions relevant to human depression.show moreshow less

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Metadaten
Author: Simona Spinelli, Tanja Müller, Miriam Friedel, Hannes Sigrist, Klaus-Peter Lesch, Mark Henkelman, Markus Rudin, Erich Seifritz, Christopher R. Pryce
URN:urn:nbn:de:bvb:20-opus-122240
Document Type:Journal article
Faculties:Medizinische Fakultät / Lehrstuhl für Molekulare Psychiatrie
Language:English
Parent Title (English):Frontiers in Behavioral Neuroscience
Year of Completion:2013
Volume:7
Pagenumber:215
Source:Frontiers in Behavioral Neuroscience 7:215. doi:10.3389/fnbeh.2013.00215
DOI:https://doi.org/10.3389/fnbeh.2013.00215
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 612 Humanphysiologie
Tag:3-dimensional MRI; 5-HTTLPR polymorphism; C57BL/6 mice; childhood maltreatment; lerned helplessness; life stress; linked polymorphic region; mouse-brain; rhesus macaques; white-matter integrity
Release Date:2016/02/25
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung