The expression of m6A enzymes in the hippocampus of diabetic cognitive impairment mice and the possible improvement of YTHDF1.

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Abstract

Cognitive impairment is a severe diabetes-related complication and seriously challenges the demand for future health resources. However, the potential therapeutic targets and mechanisms are not fully understood. Herein, we investigated the expression of the m6A enzyme in the hippocampus of mice with diabetes-induced cognitive impairment and possible improvement with overexpression of YTHDF1. A type 1 diabetes (T1D) mouse model was established by streptozotocin (STZ) intraperitoneal injection. Diabetic mice showed significant cognitive dysfunction, which was detected by novel object recognition tests and novel place recognition tests. Western blot analysis showed that compared with the control group, the protein levels of YTHDC2 and ALKBH5 were significantly upregulated in the hippocampus in the STZ group, while the expression of YTHDF1, YTHDF3 and WTAP was significantly downregulated. Furthermore, overexpression of YTHDF1 by AAV-YTHDF1 injection in the hippocampus significantly improved STZ-induced diabetic cognitive dysfunction. These results indicate that the m6A enzyme may play a key role in the cognitive dysfunction induced by diabetes, and YTHDF1 may be a promising therapeutic target.

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Author and article information

Journal

Journal ID (iso-abbrev): Brain Res

Title: Brain research

Publisher: Elsevier BV

ISSN (Electronic): 1872-6240

ISSN (Print): 0006-8993

Publication date (Electronic): Feb 15 2022

Volume: 1777

Affiliations

[1 ] The First Affiliated Hospital, Department of Endocrinology and Metabolism, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.

[2 ] The First Affiliated Hospital, Department of Endocrinology and Metabolism, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China; The First Affiliated Hospital, Institute of Clinical Medicine Center, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China. Electronic address: zuxuyu108@hotmail.com.

[3 ] The First Affiliated Hospital, Department of Endocrinology and Metabolism, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China. Electronic address: jianghua990@126.com.

Article

Publisher Item ID: S0006-8993(21)00625-9

DOI: 10.1016/j.brainres.2021.147766

PubMed ID: 34953798

SO-VID: f8ed5a80-7c38-4267-bc21-446efac61893

History

Keywords: Cognitive impairment,Type 1 diabetes,YTHDF1,m6A enzyme,mouse

Data availability:

Keywords: Cognitive impairment, Type 1 diabetes, YTHDF1, m6A enzyme, mouse

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