Alteration of dopaminergic markers in gastrointestinal tract of different rodent models of Parkinson's disease

Tian, Yuemin; Chen, X.; Luo, Ding-Zhen; Zhang, X.-H.; Xue, Hao; Zheng, Li‐Fei; Yang, Ning; Wang, X.-M.; Zhu, Jin-Xia

doi:10.1016/j.neuroscience.2008.02.033

Cited by 75 publications

(67 citation statements)

References 26 publications

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“…In fact, although ChAT-IR or HuC/D-IR appear to remain unchanged throughout the length of the GI tract (4,12,61), there was an increase in TH-IR or VIP-IR and a decrease in NOS-IR in the distal intestine (12,51,61) and an increase in dopamine-IR and dopamine transporter-IR in the stomach (51,57). Focusing on the proximal portion of the GI tract, we confirm that, in agreement with previous studies as well as a report from patients with PD (3), in the 6-OHDA model, there appear to be no overall changes in the total number of myenteric neurons.…”

Section: Discussionmentioning

confidence: 99%

“…Very little attention, however, has been focused on the GI dysfunctions in models of toxin-mediated parkinsonian-like neurodegeneration in rats. 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%

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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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Section: Discussionmentioning

confidence: 99%

mentioning

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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“…Alterations of dopaminergic markers in the gastrointestinal (GI) tract have been observed in different rodent models of PD [79]: In 6-OHDA-treated rats, the protein levels of TH and DAT in the GI tract were significantly increased, while the mRNA levels of both were decreased. In MPTP-treated mice, the protein level of TH was significantly decreased, with atrophy of gastric epithelial cells in MPTP-treated mice, although the DAT level was not changed.…”

Section: Animal Models Of Nm Symptoms In Parkinson Diseasementioning

confidence: 99%

Synuclein deposition and non-motor symptoms in Parkinson disease

Jellinger¹

2011

Journal of the Neurological Sciences

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“…Anderson et al [2] reported a 40% reduction of dopamine neurons in the ENS of mice receiving intraperitoneal MPTP administration, without loss of cholinergic or nitrergic neurons. Recently, Tian et al [28] reported increased expression of TH and DAT in the GI tract of rats bearing bilateral lesions of the SNc obtained by stereotaxic injection of 6-hydroxydopamine (6-OHDA), a neurotoxin with selective toxicity for dopaminergic neurons [30]. Given the inhibitory nature of dopamine in the ENS, an excess of enteric dopamine production caused by 6-OHDA would have been expected to reduce the gastrointestinal propulsive motility, especially gastric emptying [28].…”

mentioning

confidence: 99%

“…Recently, Tian et al [28] reported increased expression of TH and DAT in the GI tract of rats bearing bilateral lesions of the SNc obtained by stereotaxic injection of 6-hydroxydopamine (6-OHDA), a neurotoxin with selective toxicity for dopaminergic neurons [30]. Given the inhibitory nature of dopamine in the ENS, an excess of enteric dopamine production caused by 6-OHDA would have been expected to reduce the gastrointestinal propulsive motility, especially gastric emptying [28]. The inhibitory effect of dopamine is exerted through activation of prejunctional D 2 receptors located on cholinergic neurons leading to delayed gastric emptying.…”

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confidence: 99%

Functional and neurochemical changes of the gastrointestinal tract in a rodent model of Parkinson's disease

Blandini¹,

Balestra

Levandis³

et al. 2009

Neuroscience Letters

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a b s t r a c tPatients with Parkinson's disease develop motor disturbances often accompanied by peripheral autonomic dysfunctions, including gastrointestinal disorders, such as dysphagia, gastric stasis and constipation. While the mechanisms subserving enteric autonomic dysfunctions are not clearly understood, they may involve the enteric dopaminergic and/or nitrergic systems. In the present study, we demonstrate that rats with unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons develop a marked inhibition of propulsive activity compared to sham-operated controls, as indicated by a 60% reduction of daily fecal output at the 4th week of observation. Immunohistochemical data revealed that 6-hydroxydopamine treatment did not affect the total number of HuC/D-positive myenteric neurons in both the proximal and distal segments of ileum and colon. Conversely, in the distal ileum and proximal colon the number of nitrergic neurons was significantly reduced. These results suggest that a disturbed distal gut transit, reminiscent of constipation in the clinical setting, may occur as a consequence of a reduced propulsive motility, likely due to an impairment of a nitric oxide-mediated descending inhibition during peristalsis.

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Alteration of dopaminergic markers in gastrointestinal tract of different rodent models of Parkinson's disease

Cited by 75 publications

References 26 publications

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

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

Synuclein deposition and non-motor symptoms in Parkinson disease

Functional and neurochemical changes of the gastrointestinal tract in a rodent model of Parkinson's disease

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