Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson's disease

Greene, James G.; Noorian, Ali Reza; Srinivasan, Shanthi

doi:10.1016/j.expneurol.2009.04.023

Cited by 146 publications

(122 citation statements)

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“…The stool water content was then calculated as an indicator of colon water absorption. The results were normalized to body weight (adapted from a method described in Li et al and Greene et al [24,25] www.fhc.viamedica.pl free access to pre-weighed food for sixty minutes. Thirty minutes later, the animals were euthanized via decapitation, and the stomach was excised and weighed, then dried using filter paper after removal of its contents and weighed again.…”

Section: Methodsmentioning

confidence: 99%

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

Kurnik

Gil

Gajda

et al. 2015

Folia Histochem Cytobiol.

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Introduction. Impairment of the enteric nervous system has been suggested to occur within the pathogenesis of neurodegenerative diseases. Thus, in the current study, we consider salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL) as a substance that can potentially induce myenteric neurodegeneration. Material and methods. Male Wistar rats were subjected to continuous intraperitoneal dosing of salsolinol (200 mg/kg in total) with osmotic mini-pumps for either two or four weeks. An equivalent group of rats served as the control. Jejunal myenteric neurons were subjected to immunofluorescence staining to detect neuron specific protein -protein gene product (pan-neuronal marker, PGP 9.5), nitric oxide synthase (NOS), choline acetyltransferase (ChAT), Bax-protein and alpha-synuclein. In search of any functional impairment within the gastrointestinal tract, gut motility was assessed by determining the residual solid food contents in the stomach and the small and large intestine transit. Results. The myenteric neuron count, the mean size of the neuron body, the area of ganglia and the diameter of nerve strands were decreased in both of the salsolinol-treated groups compared with the controls. The number of NOS-positive cells was lower in the salsolinol-treated groups, while the number of ChAT-positive cells remained unchanged in comparison with the controls. Neurons expressing the pro-apoptotic Bax protein and alpha-synuclein deposits were observed among the myenteric neurons of the salsolinol-treated rats. Conclusions. Salsolinol evokes enteric neuronal cell death via initiation of apoptosis and leads to the formation of pathological aggregates of alpha-synuclein. Impairment of myenteric neurons, mainly the inhibitory motor neurons, might be responsible for the abnormal intestinal transit. Thus, salsolinol might be regarded as a suitable compound for inducing experimental enteric neurodegeneration in rats.

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Section: Methodsmentioning

confidence: 99%

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

Kurnik

Gil

Gajda

et al. 2015

Folia Histochem Cytobiol.

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“…The mean weight of rats in the control group increased throughout the research period; whereas rats in the rotenone group exhibited weight loss in the first 4 weeks, followed by a weight increase until the 12th week and a gradual decrease between weeks 16-24. Rats in the rotenone rat model exhibited obvious weight loss, which was regarded to be associated with the damage to gastrointestinal neurons (13,14), which impede digestion. This symptom of weight loss also manifests in patients with PD (15,16).…”

Section: Rotenone Treatment Induces Behavioral Deficits and Mortalitymentioning

confidence: 99%

Rotenone-induced energy stress decompensated in ventral mesocerebrum is associated with Parkinsonism progression in rats

Bai

Tang³

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Parkinson's disease (PD) is the second most common neurodegenerative disorder, which is characterized by the hallmark feature of loss of dopaminergic neurons in the substantia nigra. Energy metabolic disorder is associated with the pathogenesis of PD; however, the development of this disorder is yet to be elucidated. PD-like characteristics have been demonstrated in a rotenone rat model. In the present study, energy metabolism status was investigated in a rat model following intraperitoneal treatment with 1.0 mg/kg rotenone every 48 h. The behavior and tyrosine hydroxylase-positive levels in the substantia nigra of rats that were treated with rotenone for 24 weeks demonstrated that these rats developed more severe parkinsonism, as compared with that were treated for 16 weeks. Detection of ATP, lactic acid, NADH dehydrogenase 1 mRNA and lactate dehydrogenase B mRNA levels in the ventral mesocerebrum (VM) and skeletal muscle (SM) of the rats that had been treated with rotenone for 16 and 24 weeks demonstrated that the energy stress induced by rotenone progressed in both VM and SM. Notably, the energy stress detected in VM was more severe, and this energy stress was decompensated in the VM of rats that had been treated with rotenone for 24 weeks. The progression of energy stress and the incidence of energy decompensation in VM may be important for the improvement of PD pathology. IntroductionParkinson's disease (PD) is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra. PD is the most common neurodegenerative movement disorder, affecting >1% of the population that are aged >60 (1). Current treatments, such as pharmaceutical agents or deep brain stimulation predominantly target the symptoms and are unable to attenuate or reverse the progression of this disease (2). Understanding PD at a cellular and molecular level is important to determine novel targets and develop neuroprotective and disease-modifying therapeutic strategies. Although the causes and potential factors remain unknown, environmental factors may have a critical role, such as herbicides or pesticides, organic solvents, carbon monoxide and carbon disulfide (3,4). Notably, various studies have suggested that PD is associated with energy metabolism defects (5-7).Due to their structure, physiologic activities and high oxidative level of DA metabolism, DA cells in the substantia nigra are energy demanding and prone to energy stress (8). Furthermore, these cells have a relative low capacity for glycolysis compensation and lower glutathione levels (9,10), which ensures that they cannot respond appropriately to energy stress and are thus sensitive to energy disturbances.Rotenone is a common insecticide and mitochondria complex 1 inhibitor, which is used to induce chronic rotenone rat models with PD-associated features that manifest as DA cells are selectively damaged (11). However, how energy stress is induced and associated with the development of PD-associated in this model remains unknown.In the present study, rats were ...

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“…Indeed, Greene et al [17] reported that rats chronically treated with systemic rotenone, a mitochondrial toxin that replicates PD features in rodents [4], showed a transient decrease in stool frequency and weight loss. Aphagia and weight loss have been described in rotenone-treated animals [4,14] and may play a major role in the decreased stool frequency observed in this model.…”

mentioning

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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Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson's disease

Cited by 146 publications

References 48 publications

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

Rotenone-induced energy stress decompensated in ventral mesocerebrum is associated with Parkinsonism progression in rats

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

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