Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats
The cholinergic anti-inflammatory pathway (CAIP) has been proposed to regulate gastrointestinal inflammation via acetylcholine released from the vagus nerve activating α7 nicotinic receptor (α7nAChR) on macrophages. Parkinson’s disease (PD) patients and PD rats with substantia nigra (SN) lesions exh...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/40fb9f53f4334682a5787ec4891333b7 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:40fb9f53f4334682a5787ec4891333b7 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:40fb9f53f4334682a5787ec4891333b72021-11-22T07:18:54ZActivation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats1663-981210.3389/fphar.2021.793374https://doaj.org/article/40fb9f53f4334682a5787ec4891333b72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.793374/fullhttps://doaj.org/toc/1663-9812The cholinergic anti-inflammatory pathway (CAIP) has been proposed to regulate gastrointestinal inflammation via acetylcholine released from the vagus nerve activating α7 nicotinic receptor (α7nAChR) on macrophages. Parkinson’s disease (PD) patients and PD rats with substantia nigra (SN) lesions exhibit gastroparesis and a decayed vagal pathway. To investigate whether activating α7nAChR could ameliorate inflammation and gastric dysmotility in PD rats, ELISA, western blot analysis, and real-time PCR were used to detect gastric inflammation. In vitro and in vivo gastric motility was investigated. Proinflammatory mediator levels and macrophage numbers were increased in the gastric muscularis of PD rats. α7nAChR was located on the gastric muscular macrophages of PD rats. The α7nAChR agonists PNU-282987 and GTS-21 decreased nuclear factor κB (NF-κB) activation and monocyte chemotactic protein-1 mRNA expression in the ex vivo gastric muscularis of PD rats, and these effects were abolished by an α7nAChR antagonist. After treatment with PNU-282987 in vivo, the PD rats showed decreased NF-κB activation, inflammatory mediator production, and contractile protein expression and improved gastric motility. The present study reveals that α7nAChR is involved in the development of gastroparesis in PD rats and provides novel insight for the treatment of gastric dysmotility in PD patients.Li ZhouLi ZhouLi-Fei ZhengXiao-Li ZhangZhi-Yong WangYuan-Sheng YaoXiao-Lin XiuChen-Zhe LiuYue ZhangXiao-Yan FengJin-Xia ZhuFrontiers Media S.A.articleα7nAChR6-hydroxydopaminegastric inflammationmacrophageParkinson’s diseaseTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
α7nAChR 6-hydroxydopamine gastric inflammation macrophage Parkinson’s disease Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
α7nAChR 6-hydroxydopamine gastric inflammation macrophage Parkinson’s disease Therapeutics. Pharmacology RM1-950 Li Zhou Li Zhou Li-Fei Zheng Xiao-Li Zhang Zhi-Yong Wang Yuan-Sheng Yao Xiao-Lin Xiu Chen-Zhe Liu Yue Zhang Xiao-Yan Feng Jin-Xia Zhu Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats |
| description |
The cholinergic anti-inflammatory pathway (CAIP) has been proposed to regulate gastrointestinal inflammation via acetylcholine released from the vagus nerve activating α7 nicotinic receptor (α7nAChR) on macrophages. Parkinson’s disease (PD) patients and PD rats with substantia nigra (SN) lesions exhibit gastroparesis and a decayed vagal pathway. To investigate whether activating α7nAChR could ameliorate inflammation and gastric dysmotility in PD rats, ELISA, western blot analysis, and real-time PCR were used to detect gastric inflammation. In vitro and in vivo gastric motility was investigated. Proinflammatory mediator levels and macrophage numbers were increased in the gastric muscularis of PD rats. α7nAChR was located on the gastric muscular macrophages of PD rats. The α7nAChR agonists PNU-282987 and GTS-21 decreased nuclear factor κB (NF-κB) activation and monocyte chemotactic protein-1 mRNA expression in the ex vivo gastric muscularis of PD rats, and these effects were abolished by an α7nAChR antagonist. After treatment with PNU-282987 in vivo, the PD rats showed decreased NF-κB activation, inflammatory mediator production, and contractile protein expression and improved gastric motility. The present study reveals that α7nAChR is involved in the development of gastroparesis in PD rats and provides novel insight for the treatment of gastric dysmotility in PD patients. |
| format |
article |
| author |
Li Zhou Li Zhou Li-Fei Zheng Xiao-Li Zhang Zhi-Yong Wang Yuan-Sheng Yao Xiao-Lin Xiu Chen-Zhe Liu Yue Zhang Xiao-Yan Feng Jin-Xia Zhu |
| author_facet |
Li Zhou Li Zhou Li-Fei Zheng Xiao-Li Zhang Zhi-Yong Wang Yuan-Sheng Yao Xiao-Lin Xiu Chen-Zhe Liu Yue Zhang Xiao-Yan Feng Jin-Xia Zhu |
| author_sort |
Li Zhou |
| title |
Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats |
| title_short |
Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats |
| title_full |
Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats |
| title_fullStr |
Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats |
| title_full_unstemmed |
Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats |
| title_sort |
activation of α7nachr protects against gastric inflammation and dysmotility in parkinson’s disease rats |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/40fb9f53f4334682a5787ec4891333b7 |
| work_keys_str_mv |
AT lizhou activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats AT lizhou activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats AT lifeizheng activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats AT xiaolizhang activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats AT zhiyongwang activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats AT yuanshengyao activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats AT xiaolinxiu activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats AT chenzheliu activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats AT yuezhang activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats AT xiaoyanfeng activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats AT jinxiazhu activationofa7nachrprotectsagainstgastricinflammationanddysmotilityinparkinsonsdiseaserats |
| _version_ |
1718417850336542720 |