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miR-1202 是一种灵长类动物特异性且富含大脑的 microRNA,与重度抑郁症和抗抑郁治疗有关。

miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment.

机构信息

McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

出版信息

Nat Med. 2014 Jul;20(7):764-8. doi: 10.1038/nm.3582. Epub 2014 Jun 8.

Abstract

Major depressive disorder (MDD) is a prevalent mood disorder that is associated with differential prefrontal brain expression patterns. Treatment of MDD includes a variety of biopsychosocial approaches. In medical practice, antidepressant drugs are the most common treatment for depressive episodes, and they are among the most prescribed medications in North America. Although antidepressants are clearly effective, particularly for moderate to severe depressive episodes, there is variability in how individuals respond to antidepressant treatment. Failure to respond has individual, economic and social consequences for patients and their families. Several lines of evidence demonstrate that genes are regulated through the activity of microRNAs (miRNAs), which act as fine-tuners and on-off switches of gene expression. Here we report on complementary studies using postmortem human brain samples, cellular assays and samples from clinical trials of patients with depression and show that miR-1202, a miRNA specific to primates and enriched in the human brain, is differentially expressed in individuals with depression. Additionally, miR-1202 regulates expression of the gene encoding metabotropic glutamate receptor-4 (GRM4) and predicts antidepressant response at baseline. These results suggest that miR-1202 is associated with the pathophysiology of depression and is a potential target for new antidepressant treatments.

摘要

重度抑郁症(MDD)是一种常见的情绪障碍,与前额叶大脑表达模式的差异有关。MDD 的治疗包括各种生物心理社会方法。在医学实践中,抗抑郁药是治疗抑郁发作最常用的方法,也是北美开处方最多的药物之一。尽管抗抑郁药显然有效,特别是对中度至重度抑郁发作,但个体对抗抑郁治疗的反应存在差异。对患者及其家属而言,治疗反应不佳会产生个人、经济和社会后果。有几条证据表明,基因是通过 microRNAs(miRNAs)的活性来调节的,miRNAs 作为基因表达的微调器和开/关开关。在这里,我们报告了使用死后人脑样本、细胞测定和抑郁症患者临床试验样本进行的补充研究,并表明 miR-1202,一种特异性存在于灵长类动物和富含人脑的 miRNA,在抑郁症患者中存在差异表达。此外,miR-1202 调节代谢型谷氨酸受体 4(GRM4)基因的表达,并预测基线时的抗抑郁反应。这些结果表明,miR-1202 与抑郁症的病理生理学有关,是新的抗抑郁治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72a5/4087015/0b59fab1fc3d/nihms4401f1.jpg

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