Abstract
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.
Highlights
Gastroparesis and constipation are prominent nonmotor symptoms of Parkinson’s disease (PD), and these symptoms often occur decades before somatic motor symptoms (Cersosimo and Benarroch, 2012; Matteoli and Boeckxstaens, 2013)
The results showed that the increased expression of inducible nitric oxide synthase (iNOS) in the gastric muscularis of 6-OHDA rats was prevented by early
We found that the levels of both α-smooth muscle actin (α-SMA) and myosin light chain 20 (MLC20) were significantly decreased in 6-OHDA rats, but eary-PNU treatment restored the level of both α-SMA and MLC20 (Figure 4C)
Summary
Gastroparesis and constipation are prominent nonmotor symptoms of Parkinson’s disease (PD), and these symptoms often occur decades before somatic motor symptoms (Cersosimo and Benarroch, 2012; Matteoli and Boeckxstaens, 2013). It is unclear whether the relevant neuronal structures, including brain stem nuclei, the autonomic nervous system, and the enteric nervous system, are individually or collaboratively involved in gastroparesis in PD (Fedorova et al, 2017). Given the anti-inflammatory effect of ACh, we recently reported the occurrence of gastric muscularis inflammation in 6OHDA rats (Xiu et al, 2020)
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