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Cited by 66Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorTryptophan and brain disorders

Genome-wide expression profiling of human lymphoblastoid cell lines implicates integrin beta-3 in the mode of action of antidepressants

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Oved, K, Morag, A, Pasmanik-Chor, M, Rehavi, M, Shomron, N, Gurwitz, D·2013·Translational Psychiatry
DOI 10.1038/tp.2013.86PMC PMC3818017
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Abstract

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depression. However, the link between inhibition of serotonin reuptake and remission from depression remains controversial: in spite of the rapid onset of serotonin reuptake inhibition, remission from depression takes several weeks, presumably reflecting synaptogenesis/neurogenesis and neuronal rewiring. We compared genome-wide expression profiles of human lymphoblastoid cell lines from unrelated individuals following treatment with 1 μM paroxetine for 21 days with untreated control cells and examined which genes and microRNAs (miRNAs) showed the most profound and consistent expression changes. ITGB3, coding for integrin beta-3, showed the most consistent altered expression (1.92-fold increase, P=7.5 × 10(-8)) following chronic paroxetine exposure. Using genome-wide miRNA arrays, we observed a corresponding decrease in the expression of two miRNAs, miR-221 and miR-222, both predicted to target ITGB3. ITGB3 is crucial for the activity of the serotonin transporter (SERT), the drug target of SSRIs. Moreover, it is presumably required for the neuronal guidance activity of CHL1, whose expression was formerly identified as a tentative SSRI response biomarker. Further genes whose expression was significantly modulated by chronic paroxetine are also implicated in neurogenesis. Surprisingly, the expression of SERT or serotonin receptors was not modified. Our findings implicate ITGB3 in the mode of action of SSRI antidepressants and provide a novel link between CHL1 and the SERT. Our observations suggest that SSRIs may relieve depression primarily by promoting neuronal synaptogenesis/neurogenesis rather than by modulating serotonin neurotransmission per se.

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Authors
Oved, K., Morag, A., Pasmanik-Chor, M., Rehavi, M., Shomron, N., & Gurwitz, D.
Affiliations
Tel Aviv University (IL)
Corresponding author
  • Shomron, N
  • Gurwitz, D
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2013-10-15
Volume
3
Issue
10
Pages
e313-e313
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/tp.2013.86
PMC
PMC3818017
OpenAlex
W2064063710
Cited by
66
References
3
Citations by year
2025: 1 · 2024: 2 · 2023: 7 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 9 · 2017: 8 · 2016: 8 · 2015: 8 · 2014: 6
FWCI
5.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Israel Cancer Research Fund
  • Friends For an Earlier Breast Cancer Test
  • Tel Aviv University
  • Office of the Chief Scientist, Ministry of Health
  • Israeli Centers for Research Excellence
  • Planning and Budgeting Committee of the Council for Higher Education of Israel
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
CD61, selective serotonin reuptake inhibitors, paroxetine, antidepressant mechanism, serotonin transporter, CHL1, microRNA, miR-221, miR-222, neurogenesis, synaptogenesis, major depressive disorder, lymphoblastoid cell lines, gene expression profiling
MeSH terms
Cell Line, Humans, Lymphocytes, RNA, Messenger, Cell Adhesion Molecules, Selective Serotonin Reuptake Inhibitors, Paroxetine, Sequence Analysis, RNA, Gene Expression Profiling, MicroRNAs, Integrin beta3, Serotonin Plasma Membrane Transport Proteins, Neurogenesis, Real-Time Polymerase Chain Reaction

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