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Expression analysis for inverted effects of serotonin transporter inactivation |
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| Authors: | Ichikawa Manabu Okamura-Oho Yuko Shimokawa Kazuro Kondo Shinji Nakamura Sakiko Yokota Hideo Himeno Ryutaro Lesch Klaus-Peter Hayashizaki Yoshihide |
| Affiliation: | a Genome Exploration Research Group, RIKEN Genomic Sciences Center (GSC), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan b Division of Genomic Information Resources, Science of Biological Supramolecular Systems, Graduate School of Integrated Science, Yokohama City University, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan c Computational Biomechanics Unit, Discovery Research Institute, RIKEN, 2-1 Hirosawa Wako City, Saitama 351-0198, Japan d Bio-research Infrastructure Construction Team, V-CAD System Research, Program, Center for Intellectual Property Strategies, RIKEN, 2-1 Hirosawa Wako City, Saitama 351-0198, Japan e Molecular and Clinical Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg Füchsleinstr. 15, 97080 Würzburg, Germany |
| Abstract: | Inactivation of serotonin transporter (HTT) by pharmacologically in the neonate or genetically increases risk for depression in adulthood, whereas pharmacological inhibition of HTT ameliorates symptoms in depressed patients. The differing role of HTT function during early development and in adult brain plasticity in causing or reversing depression remains an unexplained paradox. To address this we profiled the gene expression of adult Htt knockout (Htt KO) mice and HTT inhibitor-treated mice. Inverted profile changes between the two experimental conditions were seen in 30 genes. Consistent results of the upstream regulatory element search and the co-localization search of these genes indicated that the regulation may be executed by Pax5, Pax7 and Gata3, known to be involved in the survival, proliferation, and migration of serotonergic neurons in the developing brain, and these factors are supposed to keep functioning to regulate downstream genes related to serotonin system in the adult brain. |
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