Elevated exosomal secretion of miR-124-3p from spinal neurons positively associates with disease severity in ALS.
Elevated exosomal secretion of miR-124-3p from spinal neurons positively associates with disease severity in ALS.
复制标题
DOI：
10.1016/j.expneurol.2020.113414
复制
发表时间：
2020-11
影响因子：
5.3
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Yelick J;Men Y;Jin S;Seo S;Espejo-Porras F;Yang Y
MicroRNAs(MiRs)是中枢神经系统发育和疾病的强大调节因子。血浆和脑脊液(CSF)miRs最近被认为是开发生物标记物的潜在新来源。我们以前的研究表明，miR-124-3p是神经元识别所必需的miR，在神经元外体中含量很高，在ALS模型SOD1G93A小鼠的脊髓中表达减少。在目前的研究中，我们通过原位杂交发现疾病相关的miR-124-3p水平降低，尤其是在脊髓神经元中。通过使用我们最近开发的exosome报告小鼠与坐骨神经注射相结合，我们观察到在SOD1G93A小鼠中，即使在症状前期阶段，miR-124-3p与脊髓运动神经元衍生的exosome的关联性也增加了。在SOD1G93A小鼠中，坐骨神经注射传递miR-124-3p也更常定位于脊髓运动神经元之外。随后对ALS患者脑脊液外体miR-124-3p水平的定量分析发现，脑脊液外体miR-124-3p水平与(男性)ALS患者的疾病分期(以ALSFRS-R评分为准)显著相关。这些结果为脑脊液外体miR-124-3p作为ALS疾病分期指标的潜在应用提供了初步证据。
MicroRNAs (miRs) are powerful regulators of CNS development and diseases. Plasma and cerebrospinal fluid (CSF) miRs have recently been implicated as potential new sources for biomarker development. Previously we showed that miR-124–3p, an essential miR for neuronal identity, is highly abundant in neuronal exosomes and its expression decreases in spinal cord of ALS model SOD1G93A mice. In the current study, we found a disease associated reduction of miR-124–3p levels specifically in spinal neurons using in situ hybridization. By employing our recently developed exosome reporter mice in combination with sciatic nerve injections, we observed an increased association of miR-124–3p with spinal motor neuron-derived exosomes in SOD1G93A mice, even at the pre-symptomatic stage. Sciatic nerve injection delivered miR-124–3p is also more frequently localized outside of spinal motor neurons in SOD1G93A mice. Subsequent quantitative analysis of miR-124–3p levels in CSF exosomes from ALS patients found a significant correlation between CSF exosomal miR-124–3p levels and disease stage (indicated by the ALSFRS-R score) of (male) ALS patients. These results provide preliminary evidence to support the potential use of CSF exosomal miR-124–3p as a disease stage indicator in ALS.
登录
查看更多内容
影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
--
作者：
Lafourcade C;Ramírez JP;Luarte A;Fernández A;Wyneken U
通讯作者：
Wyneken U
影响因子：
11.2
作者：
Butovsky, Oleg;Jedrychowski, Mark P.;Cialic, Ron;Krasemann, Susanne;Murugaiyan, Gopal;Fanek, Zain;Greco, David J.;Wu, Pauline M.;Doykan, Camille E.;Kiner, Olga;Lawson, Robert J.;Frosch, Matthew P.;Pochet, Nathalie;El Fatimy, Rachid;Krichevsky, Anna M.;Gygi, Steven P.;Lassmann, Hans;Berry, James;Cudkowicz, Merit E.;Weiner, Howard L.
通讯作者：
Weiner, Howard L.
DOI：
10.1126/science.aad2509
发表时间：
2015-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amin ND;Bai G;Klug JR;Bonanomi D;Pankratz MT;Gifford WD;Hinckley CA;Sternfeld MJ;Driscoll SP;Dominguez B;Lee KF;Jin X;Pfaff SL
通讯作者：
Pfaff SL
影响因子：
4.4
作者：
Cedarbaum, JM;Stambler, N;Nakanishi, A
通讯作者：
Nakanishi, A