Vogt Ina R, Lees Andrew J, Evert Bernd O, Klockgether Thomas, Bonin Michael, Wüllner Ullrich
Department of Neurology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Exp Neurol. 2006 Jun;199(2):465-78. doi: 10.1016/j.expneurol.2006.01.008. Epub 2006 Apr 19.
Multiple system atrophy (MSA) and sporadic, non-mendelian Parkinson's disease (PD) are progressive neurodegenerative disorders with overlapping clinical symptoms and pathology. The etiology of both disorders is unknown, and complex combinations of multiple susceptibility genes and environmental factors are thought to be involved. Both disorders are characterized by ubiquitous alpha-synuclein aggregates in distinct regions and cell types of the central nervous system. In PD, alpha-synuclein-positive aggregates appear to be largely neuronal while in MSA oligodendroglial inclusions prevail. In PD patients, the alpha-synuclein pathology is thought to evolve in a rather regular pattern, starting in the brainstem and olfactory bulb and extending gradually onto the substantia nigra and ultimately the cerebral cortex while the cerebellum is largely spared. MSA pathology has not been graded in a similar way yet; neuropathological analyses revealed neurodegeneration and gliosis primarily in the brainstem, midbrain and basal ganglia and the cerebellum, while the cortex is largely spared. To identify disease-specific transcriptional patterns in MSA, we chose CNS regions differentially affected in MSA and PD for comparative gene expression profiling: putamen, cerebellum and occipital cortex. Four genes were regulated in both MSA and PD putamen and twelve in MSA and PD cerebellum. Regulated transcripts were validated using real-time quantitative RT-PCR, and immunohistochemistry was performed for the most significantly downregulated transcripts in MSA and PD putamen, GPR86 and RGS14, associated with G protein signaling and transcriptional regulation.
多系统萎缩（MSA）和散发性、非孟德尔遗传性帕金森病（PD）是具有重叠临床症状和病理特征的进行性神经退行性疾病。这两种疾病的病因均不明，人们认为其涉及多个易感基因和环境因素的复杂组合。这两种疾病的特征均为中枢神经系统不同区域和细胞类型中普遍存在α-突触核蛋白聚集体。在帕金森病中，α-突触核蛋白阳性聚集体似乎主要存在于神经元中，而在多系统萎缩中，少突胶质细胞内含物占主导。在帕金森病患者中，α-突触核蛋白病理改变被认为以一种相当规律的模式发展，始于脑干和嗅球，逐渐扩展至黑质，最终累及大脑皮层，而小脑基本不受影响。多系统萎缩的病理改变尚未以类似方式进行分级；神经病理学分析显示，神经变性和胶质增生主要发生在脑干、中脑、基底神经节和小脑中，而大脑皮层基本不受影响。为了确定多系统萎缩中疾病特异性的转录模式，我们选择了在多系统萎缩和帕金森病中受影响程度不同的中枢神经系统区域进行比较基因表达谱分析：壳核、小脑和枕叶皮层。在多系统萎缩和帕金森病的壳核中有4个基因受到调控，在多系统萎缩和帕金森病的小脑中则有12个基因受到调控。使用实时定量逆转录聚合酶链反应对调控的转录本进行验证，并对多系统萎缩和帕金森病壳核中下调最显著的转录本GPR86和RGS14进行免疫组织化学检测，这两个转录本与G蛋白信号传导和转录调控相关。
