Comprehensive Epigenetic Analysis of m6A Modification in the Hippocampal Injury of Diabetic Rats

Abstract

Aim: To study RNA N6-methyladenosine (m6A) modification in the diabetic hippocampus. Methods: Behavioral tests and staining were performed to evaluate the damage to the diabetic hippocampus in model rats. Western blotting was performed to investigate the expression of methylation-related enzymes, and flow cytometry was used to demonstrate HT22 cell apoptosis. M6A and RNA sequencing analyses were conducted to profile m6A-tagged transcripts in the diabetic hippocampus. Results: The rat models of diabetes mellitus suffered from cognitive disorders and hippocampal neuron damage. High glucose levels altered the expression of methylation-related enzymes. A total of 4890 differentially methylated m6A peaks and 63 differentially expressed genes and differentially methylated m6A sites were identified. Conclusion: The findings suggest that m6A modification is altered in the diabetic hippocampus and provide new insight into diabetic hippocampal injury.

Keywords::

• apoptosis
• cognitive disorder
• diabetes mellitus
• RNA m6A methylation

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0125

Financial & competing interests disclosure

This research was supported by Shanghai Shenkang Hospital Development Center (No. SHDC12017X17), International Exchange Program for Graduate Students, Tongji University (No. 201902073), and Young Scientists Fund, National Natural Science Foundation of China (No. 81801051). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. Funding was provided by Shanghai Shenkang Hospital Development Center (No. SHDC12017X17).

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This research was supported by Shanghai Shenkang Hospital Development Center (No. SHDC12017X17), International Exchange Program for Graduate Students, Tongji University (No. 201902073), and Young Scientists Fund, National Natural Science Foundation of China (No. 81801051). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized in the production of this manuscript. Funding was provided by Shanghai Shenkang Hospital Development Center (No. SHDC12017X17).