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NR4A1 Methylation Associated Multimodal Neuroimaging Patterns Impaired in Temporal Lobe Epilepsy

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Last modified
  • 05/21/2025
Type of Material
Authors
    Dongmei Zhi, Chinese Academy of SciencesWenyue Wu, Central South UniversityBo Xiao, Central South UniversityShile Qi, Chinese Academy of SciencesRongtao Jiang, Chinese Academy of SciencesXingdong Yang, Beijing Haidian HospitalJian Yang, Beijing Institute of TechnologyWenbiao Xiao, Central South UniversityChaorong Liu, Central South UniversityHongyu Long, Central South UniversityVince D. Calhoun, Emory UniversityLili Long, Central South UniversityJing Sui, Chinese Academy of Sciences
Language
  • English
Date
  • 2020-07-14
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2020 Zhi, Wu, Xiao, Qi, Jiang, Yang, Yang, Xiao, Liu, Long, Calhoun, Long and Sui.
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Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 14
Grant/Funding Information
  • This work was partially supported by the National Natural Science Foundation (Nos. 61773380 and 81671300), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB32040100), the Beijing Municipal Science and Technology Commission (No. Z181100001518005), the Key Research Project of the Chinese Ministry of Science and Technology (No. 2016YFC0904400), the Clinical Research Foundation of Xiangya Hospital (No. 2016L08), and the National Institute of Health Grant (Nos. 1R01MH117107 and P20GM103472).
Supplemental Material (URL)
Abstract
  • DNA hypermethylation has been widely observed in temporal lobe epilepsy (TLE), in which NR4A1 knockdown has been reported to be able to alleviate seizure severity in mouse model, while the underlying methylation-imaging pathway modulated by aberrant methylation levels of NR4A1 remains to be clarified in patients with TLE. Here, using multi-site canonical correlation analysis with reference, methylation levels of NR4A1 in blood were used as priori to guide fusion of three MRI features: functional connectivity (FC), fractional anisotropy (FA), and gray matter volume (GMV) for 56 TLE patients and 65 healthy controls. Post-hoc correlations were further evaluated between the identified NR4A1-associated brain components and disease onset. Results suggested that higher NR4A1 methylation levels in TLE were related with impaired temporal-cerebellar and occipital-cerebellar FC strength, lower FA in cingulum (hippocampus), and reduced GMV in putamen, temporal pole, and cerebellum. Moreover, findings were also replicated well in both patient subsets with either right TLE or left TLE only. Particularly, right TLE patients showed poorer cognitive abilities and more severe brain impairment than left TLE patients, especially more reduced GMV in thalamus. In summary, this work revealed a potential imaging-methylation pathway modulated by higher NR4A1 methylation in TLE via data mining, which may impact the above-mentioned multimodal brain circuits and was also associated with earlier disease onset and more cognitive deficits.
Author Notes
Keywords
Research Categories
  • Biology, Neuroscience
  • Health Sciences, Medicine and Surgery

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