N6-methyladenosine RNA is modified in the rat hippocampus following traumatic brain injury with hypothermia treatment

Jin Cheng; Lian Lin; Jiangtao Yu; Xiaolu Zhu; Haoli Ma; Yan Zhao

doi:10.3389/fnins.2023.1069640

N6-methyladenosine RNA is modified in the rat hippocampus following traumatic brain injury with hypothermia treatment

Front Neurosci. 2023 Feb 15:17:1069640. doi: 10.3389/fnins.2023.1069640. eCollection 2023.

Authors

Jin Cheng^{1

2}, Lian Lin^{1

3}, Jiangtao Yu¹, Xiaolu Zhu¹, Haoli Ma⁴, Yan Zhao^{1

2}

Affiliations

¹ Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
² Hubei Clinical Research Center for Emergency and Resuscitation, Zhongnan Hospital of Wuhan University, Wuhan, China.
³ Department of Emergency, Gansu Provincial People's Hospital, Lanzhou, China.
⁴ Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.

Abstract

Recent studies have suggested a role for N6-methyladenosine (m6A) modification in neurological diseases. Hypothermia, a commonly used treatment for traumatic brain injury, plays a neuroprotective role by altering m6A modifications. In this study, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) was applied to conduct a genome-wide analysis of RNA m6A methylation in the rat hippocampus of Sham and traumatic brain injury (TBI) groups. In addition, we identified the expression of mRNA in the rat hippocampus after TBI with hypothermia treatment. Compared with the Sham group, the sequencing results of the TBI group showed that 951 different m6A peaks and 1226 differentially expressed mRNAs were found. We performed cross-linking analysis of the data of the two groups. The result showed that 92 hyper-methylated genes were upregulated, 13 hyper-methylated genes were downregulated, 25 hypo-methylated genes were upregulated, and 10 hypo-methylated genes were downregulated. Moreover, a total of 758 differential peaks were identified between TBI and hypothermia treatment groups. Among these differential peaks, 173 peaks were altered by TBI and reversed by hypothermia treatment, including Plat, Pdcd5, Rnd3, Sirt1, Plaur, Runx1, Ccr1, Marveld1, Lmnb2, and Chd7. We found that hypothermia treatment transformed some aspects of the TBI-induced m6A methylation landscape of the rat hippocampus.

Keywords: epigenetic modification; hypothermia; m6A methylation; rat hippocampus; traumatic brain injury.

Grants and funding

This study was supported by the 2021 Medical Research Project from the Health Bureau of Wuchang District of Wuhan University, the 2020 Annual Funding for Discipline Construction from Zhongnan Hospital of Wuhan University, and the Discipline Cultivation Funding from Zhongnan Hospital of Wuhan University. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.