Cingulate protein arginine methyltransferases 1 regulates peripheral hypersensitivity via fragile X messenger ribonucleoprotein

Cheng Wu; Hui-Fang Shang; Yong-Jie Wang; Jing-Hua Wang; Zhen-Xing Zuo; Yan-Na Lian; Li Liu; Chen Zhang; Xiang-Yao Li

doi:10.3389/fnmol.2023.1153870

Cingulate protein arginine methyltransferases 1 regulates peripheral hypersensitivity via fragile X messenger ribonucleoprotein

Front Mol Neurosci. 2023 Apr 20:16:1153870. doi: 10.3389/fnmol.2023.1153870. eCollection 2023.

Authors

Cheng Wu^{1

2

3

4}, Hui-Fang Shang^{3

4}, Yong-Jie Wang^{3

4}, Jing-Hua Wang^{3

4}, Zhen-Xing Zuo⁵, Yan-Na Lian^{3

4}, Li Liu⁶, Chen Zhang⁷, Xiang-Yao Li^{1

2

3

4}

Affiliations

¹ Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining, China.
² Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom.
³ International Institutes of Medicine, The Forth Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Yiwu, China.
⁴ NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
⁵ Department of Neurosurgery, Tenth People's Hospital, Shanghai, China.
⁶ Core Facilities of the School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
⁷ School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Abstract

The deficit of fragile X messenger ribonucleoprotein (FMRP) leads to intellectual disability in human and animal models, which also leads to desensitization of pain after nerve injury. Recently, it was shown that the protein arginine methyltransferases 1 (PRMT1) regulates the phase separation of FMRP. However, the role of PRMT1 in pain regulation has been less investigated. Here we showed that the downregulation of PRMT1 in the anterior cingulate cortex (ACC) contributes to the development of peripheral pain hypersensitivity. We observed that the peripheral nerve injury decreased the expression of PRMT1 in the ACC; knockdown of the PRMT1 via shRNA in the ACC decreased the paw withdrawal thresholds (PWTs) of naïve mice. Moreover, the deficits of FMRP abolished the effects of PRMT1 on pain sensation. Furthermore, overexpression of PRMT1 in the ACC increased the PWTs of mice with nerve injury. These observations indicate that the downregulation of cingulate PRMT1 was necessary and sufficient to develop peripheral hypersensitivity after nerve injury. Thus, we provided evidence that PRMT1 is vital in regulating peripheral pain hypersensitivity after nerve injury via the FMRP.

Keywords: cingulate cortex; fragile X messenger ribonucleoprotein; peripheral hypersensitivity; peripheral nerve injury; protein arginine methyltransferases 1.