miR-708-5p is elevated in bipolar patients and can induce mood disorder-associated behavior in mice.

IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Reports Pub Date : 2025-03-10 DOI:10.1038/s44319-025-00410-y
Carlotta Gilardi, Helena C Martins, Brunno Rocha Levone, Alessandra Lo Bianco, Silvia Bicker, Pierre-Luc Germain, Fridolin Gross, Ayse Özge Sungur, Theresa M Kisko, Frederike Stein, Susanne Meinert, Rainer K W Schwarting, Markus Wöhr, Udo Dannlowski, Tilo Kircher, Gerhard Schratt
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引用次数: 0

Abstract

Mood disorders (MDs) are caused by an interplay of genetic and environmental (GxE) risk factors. However, molecular pathways engaged by GxE risk factors are poorly understood. Using small-RNA sequencing in peripheral blood mononuclear cells (PBMCs), we show that the bipolar disorder (BD)-associated microRNA miR-708-5p is upregulated in healthy human subjects with a high genetic or environmental predisposition for MDs. miR-708-5p is further upregulated in the hippocampus of rats which underwent juvenile social isolation, a model of early life stress. Hippocampal overexpression of miR-708-5p in adult male mice is sufficient to elicit MD-associated behavioral endophenotypes. We further show that miR-708-5p directly targets Neuronatin (Nnat), an endoplasmic reticulum protein. Restoring Nnat expression in the hippocampus of miR-708-5p-overexpressing mice rescues miR-708-5p-dependent behavioral phenotypes. Finally, miR-708-5p is upregulated in PBMCs from patients diagnosed with MD. Peripheral miR-708-5p expression allows to differentiate male BD patients from patients suffering from major depressive disorder (MDD). In summary, we describe a potential functional role for the miR-708-5p/Nnat pathway in MD etiology and identify miR-708-5p as a potential biomarker for the differential diagnosis of MDs.

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来源期刊
EMBO Reports
EMBO Reports 生物-生化与分子生物学
CiteScore
11.20
自引率
1.30%
发文量
267
审稿时长
1 months
期刊介绍: EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry. 
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