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000140551 0247_ $$2doi$$a10.1016/j.jchemneu.2018.12.005
000140551 0247_ $$2pmid$$apmid:30557654
000140551 0247_ $$2ISSN$$a0891-0618
000140551 0247_ $$2ISSN$$a1873-6300
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000140551 037__ $$aDZNE-2020-06873
000140551 041__ $$aEnglish
000140551 082__ $$a610
000140551 1001_ $$0P:(DE-HGF)0$$aKaut, Oliver$$b0$$eCorresponding author
000140551 245__ $$a5-methylcytosine and 5-hydroxymethylcytosine in brains of patients with multiple system atrophy and patients with Parkinson's disease.
000140551 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2019
000140551 264_1 $$2Crossref$$3print$$bElsevier BV$$c2019-03-01
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000140551 520__ $$aMultiple system atrophy (MSA) is a sporadic neurodegenerative disorder of unknown etiology, characterized pathologically by α-synuclein aggregates preferentially found in oligodendroglial cells. DNA methylation has emerged as a mechanism of regulation of α-synuclein expression. Reduced 5-methylcytosine (5-mC) DNA methylation of α-synuclein has been found in the brains of patients with Parkinson's disease (PD). 5-hydroxymethylcytosine (5-hmC) methylation is another epigenetic modification of DNA. It is involved in the de-methylation of DNA, gene regulation, and DNA repair mechanisms. Here, we examined sections of human paraffin-embedded brain tissue from the cerebellum and brain stem, including the substantia nigra pars compacta, of patients with PD (n = 8) and MSA (n = 8) as well as age-matched controls (n = 8). The neocortical tissue of PD patients (n = 10) and controls (n = 10) was also examined. Using immunohistochemistry, we analyzed the expression of 5-mC and 5-hmC with an automatic, rater-independent semi-quantification method. We found a significant upregulation of 5-mC, but not 5-hmC, in cortical sections from PD patients. The brain stem and substantia nigra, and in particular the dopaminergic neurons, showed unchanged levels of both 5-mC- and 5-hmC-immunoreactivity in all groups. In the cerebellum, 5-mC was significantly decreased only in MSA patients in the granule cell layer; in contrast, 5-hmC was significantly upregulated in the cerebellar white matter of both PD and MSA patients. Our study showed different levels of expression of total 5-mC and 5-hmC methylation across different brain regions in PD and for the first time in MSA. Our results indicate that 5-mC may be relevant in MSA. The underlying mechanism of the differential 5-mC and 5-hmC expression remains unclear.
000140551 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000140551 542__ $$2Crossref$$i2019-03-01$$uhttps://www.elsevier.com/tdm/userlicense/1.0/
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000140551 650_2 $$2MeSH$$a5-Methylcytosine: analogs & derivatives
000140551 650_2 $$2MeSH$$a5-Methylcytosine: analysis
000140551 650_2 $$2MeSH$$a5-Methylcytosine: metabolism
000140551 650_2 $$2MeSH$$aAged
000140551 650_2 $$2MeSH$$aAged, 80 and over
000140551 650_2 $$2MeSH$$aBrain: metabolism
000140551 650_2 $$2MeSH$$aFemale
000140551 650_2 $$2MeSH$$aHumans
000140551 650_2 $$2MeSH$$aMale
000140551 650_2 $$2MeSH$$aMiddle Aged
000140551 650_2 $$2MeSH$$aMultiple System Atrophy: metabolism
000140551 650_2 $$2MeSH$$aParkinson Disease: metabolism
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000140551 7001_ $$aKuchelmeister, Klaus$$b1
000140551 7001_ $$0P:(DE-2719)2810422$$aMöhl, Christoph$$b2$$udzne
000140551 7001_ $$0P:(DE-2719)2000056$$aWüllner, Ullrich$$b3$$eLast author$$udzne
000140551 77318 $$2Crossref$$3journal-article$$a10.1016/j.jchemneu.2018.12.005$$b : Elsevier BV, 2019-03-01$$p41-48$$tJournal of Chemical Neuroanatomy$$v96$$x0891-0618$$y2019
000140551 773__ $$0PERI:(DE-600)2006655-7$$a10.1016/j.jchemneu.2018.12.005$$gVol. 96, p. 41 - 48$$p41-48$$q96<41 - 48$$tJournal of chemical neuroanatomy$$v96$$x0891-0618$$y2019
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000140551 9141_ $$y2019
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