Gastric smooth muscle cells manifest an abnormal phenotype in Parkinson’s disease rats with gastric dysmotility

Xiu, Xiao-Lin; Zheng, Li‐Fei; Liu, Xiaoyu; Zhu, Jin-Xia

doi:10.1007/s00441-020-03214-9

Cited by 8 publications

(7 citation statements)

References 41 publications

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“…Some groups already utilized the model to study the mechanisms of gastrointestinal dyshomeostasis in the context of the brain-first PD-like nigrostriatal lesion primarily with the focus on gastrointestinal motility (e.g. [18][19][20]). Other pathophysiological alterations such as decreased expression of the occludin barrier proteins [21] and impaired production of mucus [22] have also been reported.…”

Section: Introductionmentioning

confidence: 99%

The absence of gastrointestinal redox dyshomeostasis in the brain-first rat model of Parkinson’s disease induced by bilateral intrastriatal 6-hydroxydopamine

Homolak

Joja

Grabaric

et al. 2022

Preprint

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The gut-brain axis plays an important role in Parkinson′s disease (PD) by acting as a route for vagal propagation of aggregated α-synuclein in the gut-first endophenotype and as a mediator of gastrointestinal dyshomeostasis via the nigro-vagal pathway in the brain-first endophenotype of the disease. One important mechanism by which the gut-brain axis may promote PD is by regulating gastrointestinal redox homeostasis as overwhelming evidence suggests that oxidative stress plays a key role in the etiopathogenesis and progression of PD and the gastrointestinal tract maintains redox homeostasis of the organism by acting as a critical barrier to environmental and microbiological electrophilic challenges. The present aim was to utilize the bilateral intrastriatal 6-hydroxydopamine (6-OHDA) brain-first PD model to study the effects of isolated central pathology on redox homeostasis of the gastrointestinal tract. Three-month-old male Wistar rats were either not treated (intact controls; CTR) or treated bilaterally intrastriatally with vehicle (CIS) or 6-OHDA (6-OHDA). Motor deficits were assessed with the rotarod performance test and the duodenum, ileum, and colon were dissected for biochemical analyses 12 weeks after the treatment. Lipid peroxidation, total antioxidant capacity, low-molecular thiols, and protein sulfhydryls, the activity of total and Mn/Fe superoxide dismutases, and total and azide-insensitive catalase/peroxidase were measured. Univariate and multivariate models of redox biomarkers provide solid evidence against the existence of pronounced gastrointestinal redox dyshomeostasis. The results indicate that the dysfunction of the nigro-vagal system and not motor deficit may be a key mediator of gastrointestinal dyshomeostasis in brain-first 6-OHDA-induced rodent models of PD.

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Section: Introductionmentioning

confidence: 99%

The absence of gastrointestinal redox dyshomeostasis in the brain-first rat model of Parkinson’s disease induced by bilateral intrastriatal 6-hydroxydopamine

Homolak

Joja

Grabaric

et al. 2022

Preprint

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“…Previous studies have reported that 6-OHDA rats exhibit colonic inflammation and peritoneal macrophage polarization to the M1 proinflammatory phenotype ( Garrido-Gil et al, 2018 ). Our findings provide important evidence that 6-OHDA rats with gastroparesis also experience an obviously impaired CAIP and increased gastric muscular inflammation ( Xiu et al, 2020 ). However, mucosal inflammation is not obvious, which could be due to the predominant sympathetic innervation in the gastric mucosa ( Willemze et al, 2015 ).…”

Section: Discussionmentioning

confidence: 68%

“…The inflammatory muscular microenvironment may downregulate gastric SMC contractile protein expression in 6-OHDA rats ( Xiu et al, 2020 ). To confirm the action of α7nAChR activation on gastric SMC contractile proteins, we examined the expression of alpha-smooth muscle actin (α-SMA) and myosin light chain 20 (MLC20) in 6-OHDA rats treated with or without PNU.…”

Section: Resultsmentioning

confidence: 99%

“…Previously, we reported that a decreased number of cholinergic neurons in the DMV and a reduction in ACh content in the DMV and gastric muscularis contribute to GI dysmotility in 6-OHDA rats ( Zheng et al, 2011 ; Zheng et al, 2014 ). Given the anti-inflammatory effect of ACh, we recently reported the occurrence of gastric muscularis inflammation in 6-OHDA rats ( Xiu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats

et al. 2021

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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.

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“…1E). Xiao-Lin Xiu et al Біологічні науки [24] have shown that maximum amplitude of phasic contraction induced by carbachol in gastric SMCs of the 6-OHDA rats was decreased approximately by 60% compared to control. GSK1016790A is the selective and potent agonist of TRPV4 and it is widely used to study TRPV4 physiological function in vitro and in vivo [11].…”

Section: Research Relation Tomentioning

confidence: 99%

The Role of TRPV4 Cation Channels in Smooth Muscle Contractile Activity in Rats

Стецька¹,

Moroz²,

Dovbynchuk³

et al. 2020

Ukr. ž. med. bìol. sportu

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Although it was shown that transient receptor potential channels are expressed in the intestinal and myometrial smooth muscle cells and can control gastrointestinal motility and regulate uterine contractility the specific role of transient receptor potential vanilloid-type 4 channel in smooth muscle cells contraction remain largely unknown. The purpose of the study was to test the action of transient receptor potential vanilloid-type 4 selective agonist GSK1016790A on smooth muscle cells contraction in rat’s colon with experimental Parkinson`s disease and in the pregnant rat uterus (18-22 days of gestation). Material and methods. The Parkinson’s disease was induced by single unilateral stereotaxic injection of 12 μg 6-OHDA. The percentage of destroyed dopaminergic neurons was evaluated in apomorphine test (0.5 mg/kg, i.p.) at 1 and 2 weeks after surgery. The water content in faeces was evaluated on the 1st day, then at the 3rd week and 7th month of the experiment. The daily volume of water consumption and gastrointestinal transit time were evaluated at the 3rd week and 7th month after surgery. The action of transient receptor potential vanilloid-type 4 agonist GSK1016790A (0.3 mmol) on smooth muscle cells of colon and myometrium strips contraction was estimated by isometric tension recording. Results and discussion. The apomorphine test showed a progressive increase in the number of turns between the 1st and 2nd week after inducing 6-OHDA-PD. The water content in faeces was increased at the 3rd week (P<0.05) vs. 1st day of the experiment. The rats with 6-OHDA-PD drank less water vs. placebo and intact groups. We observed a 17% delayed GI transit time in 6-OHDA-PD rats (P<0.01) vs. intact and 21% vs. sham-lesioned group of rats 3 weeks after the 6-OHDA treatment. 7 months after the surgery GI transit time was increased more than twice in all studied groups. Transient receptor potential vanilloid-type 4 agonist action on smooth muscle cells of 6-OHDA-PD rats was reduced by 21% compared to intact group and by 46% in sham-lesioned group (P<0.05). After the application of GSK1016790A the rat myometrium strips a 28.4% (P<0.05) decrease of the contractile force was recorded. It was accompanied by a 30.7% (P<0.05) decline of the muscle work estimated as the area under the contractile curve. Suppression of the amplitude of uterine contraction was also followed by a 39.7% (P<0.05) decline of the rise time constant of peaks but unchanged peak duration at the half maximal amplitude. Conclusion. We conclude that pharmacological activation of transient receptor potential vanilloid-type 4 ion channels by their selective agonist GSK1016790A decreased the contractile activity of both colon smooth muscle cells in Parkinson’s disease rats’ model and the myometrium in pregnant rats

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Gastric smooth muscle cells manifest an abnormal phenotype in Parkinson’s disease rats with gastric dysmotility

Cited by 8 publications

References 41 publications

The absence of gastrointestinal redox dyshomeostasis in the brain-first rat model of Parkinson’s disease induced by bilateral intrastriatal 6-hydroxydopamine

The absence of gastrointestinal redox dyshomeostasis in the brain-first rat model of Parkinson’s disease induced by bilateral intrastriatal 6-hydroxydopamine

Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson’s Disease Rats

The Role of TRPV4 Cation Channels in Smooth Muscle Contractile Activity in Rats

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