Early life stress-induced miR-708-5p affects bipolar disorder-associated phenotypes through neuronatin downregulation
Early life stress-induced miR-708-5p affects bipolar disorder-associated phenotypes through neuronatin downregulation
Abstract The underlying physiological and molecular mechanisms of bipolar disorder (BD) remain largely unknown. Here, by using unbiased small RNA sequencing in peripheral blood mononuclear cells (PBMCs), we found that miR-708-5p, a microRNA that was previously associated with BD, is the most strongly upregulated microRNA in peripheral blood of both healthy human subjects with a high genetic or environmental predisposition to develop mood disorders (MDs). Furthermore, miR-708-5p is strongly upregulated in patients diagnosed with BD and has potential in conjunction with the previously identified miR-499-5p to differentiate BD patients from patients suffering from major depressive disorder (MDD) and healthy controls. miR-708 is also upregulated in the hippocampus of wild type juvenile rats that underwent social isolation, as well as in juvenile rats heterozygous for the BD risk gene Cacna1c. Furthermore, ectopic overexpression of miR-708-5p in the hippocampus of adult male mice leads to BD-associated endophenotypes, such as reduced behavioral despair, enhanced compulsivity, and short-term memory impairments. miR-708-5p directly targets Neuronatin (Nnat), an endoplasmic reticulum (ER) resident protein involved in calcium homeostasis. Restoring Nnat expression in the hippocampus of miR-708-5p overexpressing mice rescues BD-associated endophenotypes. In summary, we functionally link miR-708-5p dependent regulation of Nnat to BD, with potential implications for BD diagnosis and therapy.
Kisko Theresa M.、Kircher Tilo、Gilardi Carlotta、W?hr Markus、Martins Helena C.、Dannlowski Udo、Meinert Susanne、Gross Fridolin、Germain Pierre-Luc、Schratt Gerhard、Bianco Alessandra Lo、Schwarting Rainer K. W.、Kircher Tilo、Stein Frederike、Bicker Silvia、Sungur Ayse ?zge
Philipps-University of Marburg, Faculty of Psychology Behavioral Neuroscience||Center for Mind||KU Leuven, Faculty of Psychology and Educational Sciences, Research Unit Brain and Cognition, Laboratory of Biological Psychology, Social and Affective Neuroscience Research Group||KU Leuven, Leuven Brain InstituteDepartment of Psychiatry and Psychotherapy, University of MarburgETH Zurich, Lab of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and TechnologyPhilipps-University of Marburg, Faculty of Psychology Behavioral Neuroscience||Center for Mind||KU Leuven, Faculty of Psychology and Educational Sciences, Research Unit Brain and Cognition, Laboratory of Biological Psychology, Social and Affective Neuroscience Research Group||KU Leuven, Leuven Brain InstituteETH Zurich, Lab of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and TechnologyInstitute for Translational Psychiatry, University of M¨1nsterInstitute for Translational Psychiatry, University of M¨1nsterETH Zurich, Lab of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and TechnologyETH Zurich, Lab of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology||Laboratory of Molecular and Behavioural Neuroscience, Institute for Neuroscience, Department of Health Science and Technology||Lab of Statistical Bioinformatics, IMLS, University of Z¨1richETH Zurich, Lab of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and TechnologyETH Zurich, Lab of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and TechnologyPhilipps-University of Marburg, Faculty of Psychology Behavioral NeuroscienceDepartment of Psychiatry and Psychotherapy, University of MarburgDepartment of Psychiatry and Psychotherapy, University of MarburgETH Zurich, Lab of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and TechnologyPhilipps-University of Marburg, Faculty of Psychology Behavioral Neuroscience||Center for Mind||KU Leuven, Faculty of Psychology and Educational Sciences, Research Unit Brain and Cognition, Laboratory of Biological Psychology, Social and Affective Neuroscience Research Group||KU Leuven, Leuven Brain Institute
神经病学、精神病学基础医学分子生物学
Kisko Theresa M.,Kircher Tilo,Gilardi Carlotta,W?hr Markus,Martins Helena C.,Dannlowski Udo,Meinert Susanne,Gross Fridolin,Germain Pierre-Luc,Schratt Gerhard,Bianco Alessandra Lo,Schwarting Rainer K. W.,Kircher Tilo,Stein Frederike,Bicker Silvia,Sungur Ayse ?zge.Early life stress-induced miR-708-5p affects bipolar disorder-associated phenotypes through neuronatin downregulation[EB/OL].(2025-03-28)[2025-05-01].https://www.biorxiv.org/content/10.1101/2024.03.14.584977.点此复制
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