Alpha‐synuclein mRNA expression in oligodendrocytes in MSA. Issue 6 (3rd March 2014)

• Record Type: Journal Article
• Authors: Asi, Yasmine T.; Simpson, Julie E.; Heath, Paul R.; Wharton, Stephen B.; Lees, Andrew J.; Revesz, Tamas; Houlden, Henry; Holton, Janice L.
• Is Part Of: Glia. Volume 62:Issue 6(2014:Jun.)
• Page Start: 964
• Page End: 970
• Publication Date: 2014-03-03
• Subjects: Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.22653
• Languages: English
• ISSNs: 0894-1491

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Multiple system atrophy (MSA) is a progressive neurodegenerative disease presenting clinically with parkinsonian, cerebellar, and autonomic features. α‐Synuclein (αsyn), encoded by the gene <italic>SNCA</italic>, 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 <italic>SNCA</italic> 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. <italic>SNCA</italic> mRNA expression was not significantly different between the MSA, IPD and control cases in all regions (multilevel model, <italic>P =</italic> 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, <italic>P <</italic> 0.0001). At the cellular level, MSA oligodendrocytes expressed more <italic>SNCA</italic> 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 <italic>SNCA</italic> expression, which is higher in cortical than subcortical regions. This study is the first to demonstrate <italic>SNCA</italic> 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. GLIA 2014;62:964–970</p> </abstract>