Neuregulin 1 improved gastric motility and reduced gastric inflammation by activating the α7nAChR through the cholinergic anti-inflammatory pathway in diabetic rats

Weigang Cui; Yuqi Ma; Libin Zhang; Lei Zhang; Qianyin Yao; Jie Zhang; Yatao Cheng; Wenqin Zeng; Qin Liu; Fengyun Liu; Chunyan Liang

doi:10.1016/j.taap.2024.117205

Neuregulin 1 improved gastric motility and reduced gastric inflammation by activating the α7nAChR through the cholinergic anti-inflammatory pathway in diabetic rats

Toxicol Appl Pharmacol. 2024 Dec 15:495:117205. doi: 10.1016/j.taap.2024.117205. Online ahead of print.

Authors

Weigang Cui¹, Yuqi Ma², Libin Zhang³, Lei Zhang⁴, Qianyin Yao⁵, Jie Zhang⁵, Yatao Cheng⁵, Wenqin Zeng⁵, Qin Liu⁵, Fengyun Liu⁵, Chunyan Liang⁶

Affiliations

¹ Department of Human Anatomy, Medical college of Jiaying University, Meizhou, China; Department of Human Anatomy and histoembryology, Xinxiang Medical University, Xinxiang, China; Institute of Neuroscience and Mental Health, Medical college of Jiaying University, Meizhou, China. Electronic address: cuiweigang1978@126.com.
² Department of Human Anatomy and histoembryology, Xinxiang Medical University, Xinxiang, China; College of Pharmaceutical Sciences, Soochow University, Soochow, China.
³ Department of Physiology and Pathophysiology, Xinxiang Medical University, Xinxiang, China.
⁴ Institute of Neuroscience and Mental Health, Medical college of Jiaying University, Meizhou, China.
⁵ Department of Human Anatomy, Medical college of Jiaying University, Meizhou, China.
⁶ Library of Jiaying University, Meizhou, China.

PMID: 39689756
DOI: 10.1016/j.taap.2024.117205

Abstract

Diabetic gastroparesis (DGP), a prevalent complication of diabetes, is characterized by delayed gastric emptying and inflammation. The dorsal motor nucleus of the vagus (DMV) plays a crucial role in modulating gastric function via the vagus nerve. Neuregulin 1 (NRG1), which is present in the DMV and influences the autonomic nervous system, has an unclear role in DGP. This study aimed to investigate the expression of NRG1 in the DMV of Zucker diabetic fatty (ZDF) rats and to evaluate the impact of centrally administered NRG1 on gastric motility and inflammation, as well as the underlying mechanisms. Our findings revealed a decrease in NRG1 and choline acetyltransferase (ChAT) expression in the DMV of ZDF rats, corresponding to weakened gastric motility. Microinjection of AAV-NRG1 (overexpressed NRG1 by means of an adeno-associated viral vector delivery of NRG1) into the DMV enhanced gastric motility and increased vagal nerve discharge frequency. Moreover, AAV-NRG1 upregulated acetylcholine (Ach) and α7 nicotinic acetylcholine receptor (α7nAChR) expression in the gastric body, mitigating gastric inflammation. The beneficial effects of AAV-NRG1 were partially reversed by vagotomy or α7nAChR antagonism. These findings provide novel evidence that NRG1 in the DMV can stimulate Ach release and activate α7nAChRs, thereby reducing inflammation and restoring gastric motility via the vagus nerve. This implicates the NRG1 as a potential therapeutic target for DGP.

Keywords: Cholinergic anti-inflammatory pathway; Diabetic gastroparesis; Dorsal motor nucleus of the vagus; Neuregulin 1; ZDF rat.