Analyses of copy number and mRNA expression level of the α-synuclein gene in multiple system atrophy

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Multiple system atrophy (MSA) is a sporadic neurodegenerative disease manifested clinically by progressive ataxia, parkinsonism, and autonomic dysfunction. Its cause is unknown, and there is no curative therapy. α-synuclein is an important protein forming aggregations called glial cytoplasmic inclusions (GCIs) in oligodendroglia; these aggregations are considered important in MSA pathogenesis. Overexpression of the human α-synuclein gene in mice induces the formation of GCI-like aggregations in oligodendrocytes, leading mice to exhibit neurological signs similar to those in MSA patients. However, previous studies have excluded mutations within the coding region of the α-synuclein gene in MSA patients. To determine whether alteration in the expression level of the α-synuclein gene is associated with MSA pathogenesis, we used TaqMan quantitative PCR assay to analyze the α-synuclein gene copy number in patients’ genomes. We also used quantitative RT-PCR and in situ hybridization to analyze α-synuclein mRNA expression in MSA patients’ brain tissues. We found no alteration in the α-synuclein gene copy number in the patients’ genomes (n = 50). Quantitative analysis for α-synuclein mRNA by the TaqMan method showed that α-synuclein mRNA levels were comparable between control (n = 3) and MSA (n = 3) cerebella. On in situ hybridization, the number of neurons with α-synuclein mRNA expression was no greater in the cerebella of MSA patients (n = 3) than in the controls (n = 3). However, GCIs were seen in these MSA specimens on immunohistochemistry for α-synuclein. These results suggest that α-synuclein gene expression is not the fundamental cause of MSA.