Journal Article

DZNE-2020-06873

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 5-methylcytosine and 5-hydroxymethylcytosine in brains of patients with multiple system atrophy and patients with Parkinson's disease.

Kaut, O. (Corresponding author) ; Kuchelmeister, K. ; Möhl, C.DZNE* ; Wüllner, U. (Last author)DZNE*

2019
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jchemneu.2018.12.005

Abstract: Multiple 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.

Keyword(s): 5-Methylcytosine: analogs & derivatives (MeSH) ; 5-Methylcytosine: analysis (MeSH) ; 5-Methylcytosine: metabolism (MeSH) ; Aged (MeSH) ; Aged, 80 and over (MeSH) ; Brain: metabolism (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Multiple System Atrophy: metabolism (MeSH) ; Parkinson Disease: metabolism (MeSH)

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Contributing Institute(s):

1. Biomarker Parkinson's Disease (AG Wüllner)
2. Image and Data Analysis (CRFS-IDAF) (IDAF)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Experiment(s):

1. Image and Data Analysis Facility (CRFS-IDAF) / Bonn

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection ; Zoological Record

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