Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson's disease

Zheng, Li‐Fei; Wang, Zhiyong; Li, Xiaofeng; Jin, Song; Hong, Feng; Lian, Hui; Wang, Qian; Feng, Xuequan; Tang, Yuanyuan; Zhang, Yue; Zhu, Jin-Xia

doi:10.1016/j.brainres.2011.09.006

Cited by 64 publications

(69 citation statements)

References 34 publications

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“…Rats with lesions of SN dopaminergic neurons manifest GI dysmotility, 25,30 including gastroparesis and constipation. [22][23][24] The present study demonstrated that bilateral SN destruction enhanced colonic DA content, upregulated b 3 -AR, and downregulated D 5 and 5-HT 4 receptors in the colonic muscular layer. Our study suggests that altered colonic monoamine receptors' expression and enhanced DA content may be involved in colonic dysmotility and therefore contribute to constipation in 6-OHDA rats.…”

Section: Discussionmentioning

confidence: 83%

“…The methods used in this study have been described previously. [21][22][23][24] Briefly, animals were anesthetized with a mixture of xylazine and ketamine (13 and 87 mg/kg body weight, respectively, intraperitoneal), and placed on a Kopf stereotaxic instrument. Two holes were drilled in the skull at the following coordinates (in millimetres): anteroposterior, 25.6; mediolateral, 62.0; dorsoventral, 27.5.…”

Section: Methodsmentioning

confidence: 99%

“…Rats with 6-hydroxydopamine (6-OHDA) microinjected into the bilateral SN exhibit delayed gastric emptying and constipation and are widely used to investigate the GI dysfunction in PD. [21][22][23][24] The neurons displaying immunoreactivity for vasoactive intestinal polypeptide is degenerated in the enteric nervous system of patients with PD. 25 In addition, we have reported enhanced DA content with upregulation of D 2 receptors and b 1 -ARs in the gastric corpus of 6-OHDA rats.…”

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confidence: 99%

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Alteration of enteric monoamines with monoamine receptors and colonic dysmotility in 6-hydroxydopamine–induced Parkinson's disease rats

Zhang

Liu

et al. 2015

Translational Research

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Section: Discussionmentioning

confidence: 83%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Alteration of enteric monoamines with monoamine receptors and colonic dysmotility in 6-hydroxydopamine–induced Parkinson's disease rats

Zhang

Liu

et al. 2015

Translational Research

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“…Most of the studies have focused on the effects of neurotoxins on the ENS (4,12,15,33,38,41,51,56,57,61), and, essentially, limited information has been generated linking CNS neurodegeneration with parkinsonian gastric dysmotility. Relatively recent studies by Zheng and colleagues (58,59) show that degeneration of nigral neurons, as obtained either with administration of 6-OHDA or lipopolysaccharide in the SNpc, decreases antral motility, possibly via alterations of the neurochemical phenotype of DMV neurons; the model, however, used bilateral microinjections in the SNpc, which may limit severely the relevance of the observation because of the large array of behavioral side effects induced by the bilateral damage of SNpc (33).…”

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confidence: 99%

Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis

Toti

Travagli

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Toti L, Travagli RA. Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis. Am J Physiol Gastrointest Liver Physiol 307: G1013-G1023, 2014. First published October 2, 2014; doi:10.1152/ajpgi.00258.2014.-Idiopathic Parkinson's disease (PD) is a late-onset, chronic, and progressive motor dysfunction attributable to loss of nigrostriatal dopamine neurons. Patients with PD experience significant gastrointestinal (GI) issues, including gastroparesis. We aimed to evaluate whether 6-hydroxy-dopamine (6-OHDA)-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) induces gastric dysmotility via dysfunctions of the brain-gut axis. 6-OHDA microinjection into the SNpc induced a Ͼ90% decrease in tyrosine hydroxylase-immunoreactivity (IR) on the injection site. The [13 C]-octanoic acid breath test showed a delayed gastric emptying 4 wk after the 6-OHDA treatment. In control rats, microinjection of the indirect sympathomimetic, tyramine, in the dorsal vagal complex (DVC) decreased gastric tone and motility; this inhibition was prevented by the fourth ventricular application of either a combination of ␣1-and ␣2-or a combination of D1 and D2 receptor antagonists. Conversely, in 6-OHDA-treated rats, whereas DVC microinjection of tyramine had reduced effects on gastric tone or motility, DVC microinjection of thyrotropin-releasing hormone induced a similar increase in motility as in control rats. In 6-OHDA-treated rats, there was a decreased expression of choline acetyl transferase (ChAT)-IR and neuronal nitric oxide synthase (NOS)-IR in DVC neurons but an increase in dopamine-␤-hydroxylase-IR in the A2 area. Within the myenteric plexus of the esophagus, stomach, and duodenum, there were no changes in the total number of neurons; however, the percentage of NOS-IR neurons increased, whereas that of ChAT-IR decreased. Our data suggest that the delayed gastric emptying in a 6-OHDA rat model of PD may be caused by neurochemical and neurophysiological alterations in the brain-gut axis.brainstem; gastric motility; immunohistochemistry; Parkinson's disease IDIOPATHIC PARKINSON'S DISEASE (PD) is generally considered a movement disorder characterized by bradykinesia, rigidity, tremor, and gait/postural disorders related to the severe degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the basal ganglia. Although the movement disorder has dominated the attention of clinicians and researchers, it is becoming increasingly recognized that PD also involves a prominent nonmotor pathology. In fact, patients with PD experience a remarkably broad spectrum of prodromic nonmotor symptoms that include sleep disorders, orthostatic hypotension, and gastrointestinal (GI) dysfunctions, all of which add significantly to the overall disability caused by PD (9,22,26,33,38,42).GI symptoms, such as dysphagia, nausea, delayed gastric emptying and dysmotility, and constipation, often precede ...

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“…In regard to the results with antidopaminergic prokinetics, taking a look at Parkinson's disease can be elucidatory, because it is a quintessential prototype for central dopaminergic defi ciency. Although about a half of the patients suffering from Parkinson's disease experience reduced intestinal motility (29), it is likely because of decreased cholinergic and increased catecholaminergic stimulation (30), and dopaminergic medication (31). The study by Unger et al (32) pointed out the decrease in ghrelin signaling under this catecholaminergic and dopaminergic overstimulation, whereas it should be also noted that Karasawa et al (33) reported confl icting fi ndings in a similar experimental Parkinsonism model.…”

Section: Discussionmentioning

confidence: 99%

Prokinetics stimulate the increase of ghrelin in mice

Sagkan-Ozturk¹,

Demir²,

Öztürk³

2017

BLL

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OBJECTIVES: Intestinal motility is regulated by several neurotransmitters and neuropeptides including dopamine and acetylcholine as well as ghrelin. Metoclopramide and domperidone are long-standing treatment options for dysmotility, and erythromycin is suggested in selected patients. In the present study, we aimed to investigate the effects of mentioned prokinetics on ghrelin levels. METHODS: Serum ghrelin levels were estimated by using enzyme-linked immunoassay following a single administration of domperidone, metoclopramide, or erythromycin. RESULTS: Our results showed that both antidopaminergic and cholinergic prokinetics increase the circulating ghrelin levels. There was no signifi cant difference between enteral and parenteral control groups. Also, statistical analysis revealed that neither prokinetic was superior to the other in regard to its ghrelin stimulating effect. CONCLUSION: Conclusively, the present study demonstrated that the circulating levels of ghrelin increase by the administration of antidopaminergic and cholinergic prokinetics. Hence, this effect on ghrelin may partly be responsible for the motility-stimulating actions of domperidone, metoclopramide, and erythromycin (Fig. 2, Ref. 39). Text in PDF www.elis.sk.

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Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson's disease

Cited by 64 publications

References 34 publications

Alteration of enteric monoamines with monoamine receptors and colonic dysmotility in 6-hydroxydopamine–induced Parkinson's disease rats

Alteration of enteric monoamines with monoamine receptors and colonic dysmotility in 6-hydroxydopamine–induced Parkinson's disease rats

Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis

Prokinetics stimulate the increase of ghrelin in mice

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