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Two polygenic mouse models of major depressive disorders identify TMEM161B as a potential biomarker of disease in humans.
El Yacoubi, Malika; Altersitz, Claire; Latapie, Violaine; Rizkallah, Elari; Arthaud, Sébastien; Bougarel, Laure; Pereira, Marcela; Wierinckx, Anne; El-Hage, Wissam; Belzeaux, Raoul; Turecki, Gustavo; Svenningsson, Per; Martin, Benoît; Lachuer, Joël; Vaugeois, Jean-Marie; Jamain, Stéphane.
Afiliação
  • El Yacoubi M; Univ Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, F-94010, Créteil, France.
  • Altersitz C; Univ Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, F-94010, Créteil, France.
  • Latapie V; Univ Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, F-94010, Créteil, France.
  • Rizkallah E; Univ Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, F-94010, Créteil, France.
  • Arthaud S; SLEEP Team, CNRS UMR5292; INSERM U1028; Lyon Neuroscience Research; Center, Lyon, F-69372, France.
  • Bougarel L; University of Lyon 1, Lyon, France.
  • Pereira M; Univ Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, F-94010, Créteil, France.
  • Wierinckx A; NETRIS Pharma, Lyon, France.
  • El-Hage W; Department of Clinical Neuroscience, Karolinska Institute, Solna, Sweden.
  • Belzeaux R; ProfileXpert, SFR Santé Lyon-Est, UCBL UMS 3453 CNRS, US7 INSERM, Lyon, France.
  • Turecki G; UMR 1253, iBrain, Université de Tours, CHRU de Tours, INSERM, Tours, France.
  • Svenningsson P; Centre Expert Dépression Résistante, Fondation FondaMental, Tours, France.
  • Martin B; Pôle Universitaire de Psychiatrie, CHU de Montpellier, Montpellier, France.
  • Lachuer J; Fondation FondaMental, Créteil, F-94000, France.
  • Vaugeois JM; McGill Group for Suicide Studies, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada.
  • Jamain S; Department of Clinical Neuroscience, Karolinska Institute, Solna, Sweden.
Neuropsychopharmacology ; 49(7): 1129-1139, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38326457
ABSTRACT
Treatments are only partially effective in major depressive disorders (MDD) but no biomarker exists to predict symptom improvement in patients. Animal models are essential tools in the development of antidepressant medications, but while recent genetic studies have demonstrated the polygenic contribution to MDD, current models are limited to either mimic the effect of a single gene or environmental factor. We developed in the past a model of depressive-like behaviors in mice (H/Rouen), using selective breeding based on behavioral reaction after an acute mild stress in the tail suspension test. Here, we propose a new mouse model of depression (H-TST) generated from a more complex genetic background and based on the same selection process. We first demonstrated that H/Rouen and H-TST mice had similar phenotypes and were more sensitive to glutamate-related antidepressant medications than selective serotonin reuptake inhibitors. We then conducted an exome sequencing on the two mouse models and showed that they had damaging variants in 174 identical genes, which have also been associated with MDD in humans. Among these genes, we showed a higher expression level of Tmem161b in brain and blood of our two mouse models. Changes in TMEM161B expression level was also observed in blood of MDD patients when compared with controls, and after 8-week treatment with duloxetine, mainly in good responders to treatment. Altogether, our results introduce H/Rouen and H-TST as the two first polygenic animal models of MDD and demonstrate their ability to identify biomarkers of the disease and to develop rapid and effective antidepressant medications.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Biomarcadores / Herança Multifatorial / Transtorno Depressivo Maior / Modelos Animais de Doenças / Antidepressivos Tipo de estudo: Prognostic_studies Limite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Biomarcadores / Herança Multifatorial / Transtorno Depressivo Maior / Modelos Animais de Doenças / Antidepressivos Tipo de estudo: Prognostic_studies Limite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article