• KSBNS 2024


Original Article

Exp Neurobiol 2023; 32(3): 119-132

Published online June 30, 2023

© The Korean Society for Brain and Neural Sciences

A Glimpse into the Genome-wide DNA Methylation Changes in 6-hydroxydopamine-induced In Vitro Model of Parkinson’s Disease

Kasthuri Bai Magalingam1, Sushela Devi Somanath2 and Ammu Kutty Radhakrishnan1*

1Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Bandar Sunway 47500, 2Pathology Division, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia

Correspondence to: *To whom correspondence should be addressed.
TEL: 60-355144902, FAX: 60-355144902

Received: August 25, 2022; Revised: April 6, 2023; Accepted: May 5, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

A cell-based model of Parkinson’s disease (PD) is a well-established in vitro experimental prototype to investigate the disease mechanism and therapeutic approach for a potential anti-PD drug. The SH-SY5Y human neuroblastoma cells and 6-OHDA combo is one of the many neurotoxininduced neuronal cell models employed in numerous neuroscience-related research for discovering neuroprotective drug compounds. Emerging studies have reported a significant correlation between PD and epigenetic alterations, particularly DNA methylation. However, the DNA methylation changes of PD-related CpG sites on the 6-OHDA-induced toxicity on human neuronal cells have not yet been reported. We performed a genome-wide association study (GWAS) using Infinium Epic beadchip array surveying 850000 CpG sites in differentiated human neuroblastoma cells exposed to 6-OHDA. We identified 236 differentially methylated probes (DMPs) or 163 differentially methylated regions (DMRs) in 6-OHDA treated differentiated neuroblastoma cells than the untreated reference group with p<0.01, Δbeta cut-off of 0.1. Among 236 DMPs, hypermethylated DMPs are 110 (47%), whereas 126 (53%) are hypomethylated. Our bioinformatic analysis revealed 3 DMRs that are significantly hypermethylated and associated with neurological disorders, namely AKT1, ITPR1 and GNG7. This preliminary study demonstrates the methylation status of PD-related CpGs in the 6-OHDA-induced toxicity in the differentiated neuroblastoma cells model.

Graphical Abstract

Keywords: Parkinson’s disease, DNA methylation, GWAS, Neuroblastoma