Alpha-synuclein mRNA expression in oligodendrocytes in MSA.
Alpha-synuclein mRNA expression in oligodendrocytes in MSA.
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DOI：
10.1002/glia.22653
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发表时间：
2014-06
期刊：
影响因子：
6.2
通讯作者：
Holton, Janice L.
中科院分区：
文献类型：
--
作者：
Asi, Yasmine T.;Simpson, Julie E.;Heath, Paul R.;Wharton, Stephen B.;Lees, Andrew J.;Revesz, Tamas;Houlden, Henry;Holton, Janice L.
关键词：
多系统萎缩(MSA)是一种进行性神经退行性疾病，临床表现为帕金森氏症、小脑和自主神经特征。α基因编码的突触核蛋白(αsyn)是海绵状突起少突胶质细胞内胶质细胞质内含物的主要成分，但其蓄积方法尚未建立。本研究的目的是研究MSA中区域和细胞SNCA mRNA表达的变化，作为GCI形成的可能底物。应用定量逆转录聚合酶链式反应(QPCR)技术，对15例MSA、5例IPD和5例正常对照脑组织进行定量逆转录聚合酶链式反应(QPCR)，观察额枕区、背侧壳核、桥基和小脑的表达。为了进行细胞表达分析，通过激光捕获显微解剖从5例MSA和5例对照病例中分离出神经元和少突胶质细胞。MSA组、IPD组和对照组各区域SNCA基因表达差异均无统计学意义(多水平模型，P=0.14)。调整群体效应后，枕叶皮质表达最高，壳核表达最低(多水平模型，P<；0.0001)。在细胞水平上，MSA少突胶质细胞比对照组少突胶质细胞表达更多的SNCA，而MSA神经元的表达略低于对照组，但无统计学意义。我们已经证明了SNCA表达的地区差异，皮质高于皮质下区域。这项研究首次利用定量聚合酶链式反应证实了人死后组织中少突胶质细胞SNCA mRNA的表达，虽然没有统计学意义，但可能表明与对照组相比，MSA中SNCA mRNA的表达可能增加。
Multiple system atrophy (MSA) is a progressive neurodegenerative disease presenting clinically with parkinsonian, cerebellar, and autonomic features. α-Synuclein (αsyn), encoded by the gene SNCA, is the main constituent of glial cytoplasmic inclusion (GCI) found in oligodendrocytes in MSA, but the methods of its accumulation have not been established. The aim of this study is to investigate alterations in regional and cellular SNCA mRNA expression in MSA as a possible substrate for GCI formation. Quantitative reverse transcription polymerase chain reaction (qPCR) was performed on postmortem brain samples from 15 MSA, 5 IPD, and 5 control cases to investigate regional expression in the frontal and occipital regions, dorsal putamen, pontine base, and cerebellum. For cellular expression analysis, neurons and oligodendrocytes were isolated by laser-capture microdissection from five MSA and five control cases. SNCA mRNA expression was not significantly different between the MSA, IPD and control cases in all regions (multilevel model, P = 0.14). After adjusting for group effect, the highest expression was found in the occipital cortex while the lowest was in the putamen (multilevel model, P < 0.0001). At the cellular level, MSA oligodendrocytes expressed more SNCA than control oligodendrocytes and expression in MSA neurons was slightly lower than that in controls, however, these results did not reach statistical significance. We have demonstrated regional variations in SNCA expression, which is higher in cortical than subcortical regions. This study is the first to demonstrate SNCA mRNA expression by oligodendrocytes in human postmortem tissue using qPCR and, although not statistically significant, could suggest that this may be increased in MSA compared to controls.
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