新型小RNA的发现或可帮助开发治疗抑郁症的靶向性疗法

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Nat Med：新型小RNA的发现或可帮助开发治疗抑郁症的靶向性疗法
2014-06-11 10:14


2014年6月11日 讯 /生物谷BIOON/ --近日，来自麦基尔大学和道格拉斯学院的研究人员通过研究发现，在人类和其他灵长类动物大脑中一种小分子的水平明显低于抑郁症患者大脑中该分子的水平，相关研究刊登于国际著名杂志Nature Medicine上，该研究为开发治疗抑郁症的新型疗法提供了希望。

抑郁症是一种常见的身体残疾，当前针对该疾病有很多疗法，而针对不同患病个体寻找最为合适的疗法却需要花费很多时间和精力；这项研究中，研究者通过研究发现了一种名为miR-1202的新型小分子，其可以作为个体抑郁症的新型标志物，可帮助检测对抗抑郁症疗法有反应的个体。

研究者Turecki表示，利用来自道格拉斯-贝尔加拿大大脑库中的样本，我们检测了患抑郁症个体的大脑组织，并且将其同精神健康个体的大脑组织进行对比分析；结果显示，在人类和其他灵长类动物大脑中发现了一种名为miR-1202的小分子，其可以调节神经递质谷氨酸盐的重要受体。

随后研究人员进行了一系列实验发现抗抑郁剂可以改变这种小RNA分子的水平，在对使用西酞普兰治疗抑郁症的患者进行临床研究中研究人员发现，相比非抑郁症患者，抑郁症患者大脑中的miR-1202在疗法使用之前水平较低，而随着疗法的进行miR-1202的水平逐渐增加。

抗抑郁症药物是用于治疗抑郁发作的常用疗法，尽管其表现出较好的疗效，但是不同患者对抑郁症的疗法表现各异，而本文中研究者又发现miR-1202分子在抑郁症患者大脑中的水平也并不一样，尤其是那些最终对抗抑郁疗法产生反应的患者。该项研究对于开发治疗抑郁症的新型靶向性疗法提供了一定的研究数据和思路。



doi:10.1038/nm.3582
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miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment

Juan Pablo Lopez, Raymond Lim, Cristiana Cruceanu, Liam Crapper, Caroline Fasano, Benoit Labonte, Gilles Maussion, Jennie P Yang, Volodymyr Yerko, Erika Vigneault, Salah El Mestikawy, Naguib Mechawar, Paul Pavlidis & Gustavo Turecki

Major depressive disorder (MDD) is a prevalent mood disorder that is associated with differential prefrontal brain expression patterns1. 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 America2, 3. 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 families4. 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 expression5, 6, 7. 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.