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Evidence of Oropharyngeal Dysfunction in Feeding in the Rat Rotenone Model of Parkinson's Disease.

ABSTRACT: Swallowing disorders in Parkinson's disease are not responsive to dopamine depletion therapy and contribute to morbidity. They are poorly understood owing to a lack of adequate models. We present the first evidence of oropharyngeal changes in a rotenone toxicity model of Parkinson's disease. Rats were recorded while feeding before and after daily rotenone injections at two different doses (2.75?mg/kg and 3?mg/kg). The higher dose had a much more severe parkinsonian phenotype than the low dose. Timing and amplitude of chewing changed, as did the coordination of chewing and swallowing. Dose-dependent effects were evident. These preliminary results indicate that future research in toxicological models of Parkinson's disease should incorporate the study of oropharyngeal dysfunction. A better understanding of nongenetic models of Parkinson's disease in feeding may open new avenues for research into the neurological and behavioral bases for swallowing dysfunction in Parkinson's disease.

SUBMITTER: Gould FDH

PROVIDER: S-EPMC5866867 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Evidence of Oropharyngeal Dysfunction in Feeding in the Rat Rotenone Model of Parkinson's Disease.

Gould François D H FDH Gross Andrew A German Rebecca Z RZ Richardson Jason R JR

Parkinson's disease 20180311

Swallowing disorders in Parkinson's disease are not responsive to dopamine depletion therapy and contribute to morbidity. They are poorly understood owing to a lack of adequate models. We present the first evidence of oropharyngeal changes in a rotenone toxicity model of Parkinson's disease. Rats were recorded while feeding before and after daily rotenone injections at two different doses (2.75 mg/kg and 3 mg/kg). The higher dose had a much more severe parkinsonian phenotype than the low dose. T ...[more]

PMID: 29713446

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Project description:Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. Dopamine (DA) replacement therapy is one of the most effective drug treatments for PD; however, long-term levodopa treatment can lead to various side effects that negatively impact the quality of life of patients. Therefore, finding safe and effective alternative drugs to treat PD is of clinical importance. The Bushen-Jianpi decoction (BSJPD) was derived from classic traditional Chinese medicine and has been shown to be effective in the treatment of PD. This study explored the effects and mechanisms of action of BSJPD in PD. In our study, rats were randomly divided into six groups: the vehicle group, rotenone (ROT) + Saline group, ROT + low-dose BSJPD group, ROT + high-dose BSJPD group, ROT + Madopar group, and ROT + low-dose BSJPD + Madopar group. Treatment was administered to the rats once a day for 28 days, and behavioral tests were assessed. Tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT), monoamine oxidase B (MAO-B), dopa decarboxylase (DDC), alpha-synuclein (α-syn), and heme oxygenase-1 (HO-1) levels were detected. Our results show that BSJPD increases the body weight of rats, improves their motor coordination, reverses decreasing TH levels in the SN, and increases the expression level of DDC and HO-1 in the striatum (ST), but it fails to affect TH levels in the ST in the PD model. In addition, BSJPD reduced the expression of MAO-B in the ST in the PD model, but it did not have a significant effect on COMT. Rather, COMT in the plasma and liver increased in the low-dose BSJPD treatment group. Upregulation of α-syn in the PD model was also observed, but BSJPD has shown no obvious effect to clear it. Our results suggest that BSJPD exhibits a therapeutic effect on PD and may play a neuroprotective role by regulating HO-1 expression and participating in the metabolic process of DA.

Project description:BackgroundCognitive decline occurs frequently in Parkinson's disease (PD), which greatly decreases the quality of life of patients. However, the mechanisms remain to be investigated. Neuroinflammation mediated by overactivated microglia is a common pathological feature in multiple neurological disorders, including PD. This study is designed to explore the role of microglia in cognitive deficits by using a rotenone-induced mouse PD model.MethodsTo evaluate the role of microglia in rotenone-induced cognitive deficits, PLX3397, an inhibitor of colony-stimulating factor 1 receptor, and minocycline, a widely used antibiotic, were used to deplete or inactivate microglia, respectively. Cognitive performance of mice among groups was detected by Morris water maze, objective recognition, and passive avoidance tests. Neurodegeneration, synaptic loss, α-synuclein phosphorylation, glial activation, and apoptosis were determined by immunohistochemistry and Western blot or immunofluorescence staining. The gene expression of inflammatory factors and lipid peroxidation were further explored by using RT-PCR and ELISA kits, respectively.ResultsRotenone dose-dependently induced cognitive deficits in mice by showing decreased performance of rotenone-treated mice in the novel objective recognition, passive avoidance, and Morris water maze compared with that of vehicle controls. Rotenone-induced cognitive decline was associated with neurodegeneration, synaptic loss, and Ser129-phosphorylation of α-synuclein and microglial activation in the hippocampal and cortical regions of mice. A time course experiment revealed that rotenone-induced microglial activation preceded neurodegeneration. Interestingly, microglial depletion by PLX3397 or inactivation by minocycline significantly reduced neuronal damage and α-synuclein pathology as well as improved cognitive performance in rotenone-injected mice. Mechanistically, PLX3397 and minocycline attenuated rotenone-induced astroglial activation and production of cytotoxic factors in mice. Reduced lipid peroxidation was also observed in mice treated with combined PLX3397 or minocycline and rotenonee compared with rotenone alone group. Finally, microglial depletion or inactivation was found to mitigate rotenone-induced neuronal apoptosis.ConclusionsTaken together, our findings suggested that microglial activation contributes to cognitive impairments in a rotenone-induced mouse PD model via neuroinflammation, oxidative stress, and apoptosis, providing novel insight into the immunopathogensis of cognitive deficits in PD.

Dataset Information

Evidence of Oropharyngeal Dysfunction in Feeding in the Rat Rotenone Model of Parkinson's Disease.

Publications

Evidence of Oropharyngeal Dysfunction in Feeding in the Rat Rotenone Model of Parkinson's Disease.

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