Characterization of Cerebellum-Specific Ribosomal DNA Epigenetic Modifications in Alzheimer's Disease: Should the Cerebellum Serve as a Control Tissue After All?

TitleCharacterization of Cerebellum-Specific Ribosomal DNA Epigenetic Modifications in Alzheimer's Disease: Should the Cerebellum Serve as a Control Tissue After All?
Publication TypeJournal Article
Year of Publication2020
AuthorsFaria TC, Maldonado HL, Santos LC, Delabio R, Payão SLM, Turecki G, Mechawar N, Santana DA, Gigek CO, Lemos B, Smith MAC, Chen ES
JournalMol Neurobiol
Volume57
Issue6
Pagination2563-2571
Date Published2020 Jun
ISSN1559-1182
Abstract

Alzheimer's disease (AD) is a neurodegenerative disease, known as the most common form of dementia. In AD onset, abnormal rRNA expression has been reported to be linked in pathogenesis. Although region-specific expression patterns have previously been reported in AD, it is not until recently that the cerebellum has come under the spotlight. Specifically, it is unclear whether DNA methylation is the mechanism involved in rRNA expression regulation in AD. Hence, we sought to explore the rDNA methylation pattern of two different brain regions - auditory cortex and cerebellum - from AD and age-/sex-matched controls. Our results showed differential hypermethylation at an upstream CpG region to the rDNA promoter when comparing cerebellum controls to auditory cortex controls. This suggests a possible regulatory region from rDNA expression regulation. Moreover, when comparing between AD and control cerebellum samples, we observed hypermethylation of the rDNA promoter region as well as an increase in rDNA content. In addition, we also observed increased rRNA levels in AD compared to control cerebellum. Although still considered a pathology-free brain region, there are growing findings that continue to suggest otherwise. Indeed, cerebellum from AD has been recently described as affected by the disease, presenting a unique pattern of molecular alterations. Given that we observed that increased rDNA promoter methylation did not silence rDNA gene expression, we suggest that rDNA promoter hypermethylation is playing a protective role in rDNA genomic stability and, therefore, increasing rRNA levels in AD cerebellum.

DOI10.1007/s12035-020-01902-9
Alternate JournalMol Neurobiol
PubMed ID32232768
Grant List467484/2014-7 / / Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR) /
2015/10636-5 / / Fundação de Amparo à Pesquisa do Estado de São Paulo /
R01GM122088 / / National Institutes of Health (US) /
R01ES027981 / NH / NIH HHS / United States
R01ES027981 / NH / NIH HHS / United States