TY  - JOUR
AU  - Kaut, Oliver
AU  - Kuchelmeister, Klaus
AU  - Möhl, Christoph
AU  - Wüllner, Ullrich
TI  - 5-methylcytosine and 5-hydroxymethylcytosine in brains of patients with multiple system atrophy and patients with Parkinson's disease.
JO  - Journal of chemical neuroanatomy
VL  - 96
SN  - 0891-0618
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DZNE-2020-06873
SP  - 41-48
PY  - 2019
AB  - 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.
KW  - 5-Methylcytosine: analogs & derivatives
KW  - 5-Methylcytosine: analysis
KW  - 5-Methylcytosine: metabolism
KW  - Aged
KW  - Aged, 80 and over
KW  - Brain: metabolism
KW  - Female
KW  - Humans
KW  - Male
KW  - Middle Aged
KW  - Multiple System Atrophy: metabolism
KW  - Parkinson Disease: metabolism
LB  - PUB:(DE-HGF)16
C6  - pmid:30557654
DO  - DOI:10.1016/j.jchemneu.2018.12.005
UR  - https://pub.dzne.de/record/140551
ER  -