{"title":"Neuregulin 1通过胆碱能抗炎途径激活α7nAChR，从而改善糖尿病大鼠的胃肠蠕动并减轻胃部炎症。","authors":"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","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":" ","pages":"117205"},"PeriodicalIF":3.3000,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neuregulin 1 improved gastric motility and reduced gastric inflammation by activating the α7nAChR through the cholinergic anti-inflammatory pathway in diabetic rats.\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":23174,\"journal\":{\"name\":\"Toxicology and applied pharmacology\",\"volume\":\" \",\"pages\":\"117205\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-12-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology and applied pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.taap.2024.117205\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology and applied pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.taap.2024.117205","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Neuregulin 1 improved gastric motility and reduced gastric inflammation by activating the α7nAChR through the cholinergic anti-inflammatory pathway in diabetic rats.
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.
期刊介绍：
Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products.
Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged.
Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.
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