A non-human primate model for stable chronic Parkinson’s disease induced by MPTP administration based on individual behavioral quantification

Seo, Ji Hun; Lee, Youngjeon; Kim, Bom Sahn; Park, Junghyung; Yang, Sejung; Yoon, Hai Jeon; Yoo, Jang; Park, Hyun Soo; Hong, Jung Joo; Koo, Bon Sang; Baek, Seung Ho; Jeon, Chang Yeop; Huh, Jae Won; Kim, Young Hyun; Park, Sang Je; Won, Jinyoung; Ahn, Yu Jin; Kim, Keon-Woo; Jeong, Kang Jin; Kang, Philyong; Lee, Dong Seok; Lim, Soo Mee; Jin, Yeung Bae; Lee, Sang Rae

doi:10.1016/j.jneumeth.2018.10.037

Cited by 34 publications

(57 citation statements)

References 44 publications

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“…They showed global activity using a video-based analysis system with stable PD symptoms. Their experiments were correlated with global activity and Parkinsonian behavior scores, along with dopaminergic neuronal loss (by immunohistochemistry and western blot) in the basal ganglia [ 146 ]. Franke et al (2016) administered a total of 2.5 mg of MPTP (0.5 mg/once a day/week) subcutaneously in marmosets.…”

Section: Neurotoxins Used To Induce Pd In Vivo Modelsmentioning

confidence: 99%

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Prasad

Hung

2020

Antioxidants

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Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson’s disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer’s disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes the primary motor symptoms of resting tremor, bradykinesia, muscle rigidity, and postural instability. The risk factors of PD comprise environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular injury, aging, and hereditary defects. The pathologic features of PD include impaired protein homeostasis, mitochondrial dysfunction, nitric oxide, and neuroinflammation, but the interaction of these factors contributing to PD is not fully understood. In neurotoxin-induced PD models, neurotoxins, for instance, 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-Methyl-4-phenylpyridinium (MPP+), paraquat, rotenone, and permethrin mainly impair the mitochondrial respiratory chain, activate microglia, and generate reactive oxygen species to induce autooxidation and dopaminergic neuronal apoptosis. Since no current treatment can cure PD, using a suitable PD animal model to evaluate PD motor symptoms’ treatment efficacy and identify therapeutic targets and drugs are still needed. Hence, the present review focuses on the latest scientific developments in different neurotoxin-induced PD animal models with their mechanisms of pathogenesis and evaluation methods of PD motor symptoms.

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Section: Neurotoxins Used To Induce Pd In Vivo Modelsmentioning

confidence: 99%

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Prasad

Hung

2020

Antioxidants

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“…in this context, our present study suggests that automatic quantification of locomotion could be a useful tool to guide adjustments of mPTP treatment for better modeling, despite its limitation of not using a better-established MPTP model. Recently, we verified the individual adjustments of mPTP administration based on the results of the automatic quantification of global activity using this video-based tracking system developed stable chronic Parkinson's disease in monkeys [27]. Therefore, we believe that assessment of locomotor behavior using our automated video tracking system may offer an effective approach for studies using large animals.…”

Section: Discussionmentioning

confidence: 74%

“…Characterization and validation of the mPTP-induced animal models for Parkinson's disease have been ongoing for the past 2 decades, and still requires further research [24,27]. Therefore, it is necessary to attempt several protocols, including variations in doses, delivery routes, and injection schedules.…”

Section: Discussionmentioning

confidence: 99%

A pilot study on assessment of locomotor behavior using a video tracking system in minipigs

et al. 2020

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Pigs are often selected for large animal models including for neuroscience and behavioral research, because their anatomy and biochemistry are similar to those of humans. However, behavioral assessments, in combination with objective long-term monitoring, is difficult. In this study, we introduced an automated video tracking system which was previously used in rodent studies, for use with pig models. Locomotor behaviors (total distance, number of zone transitions, and velocity) were evaluated and their changes were validated by different 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration methods and dosing regimens. Three minipigs (23-29 kg) received subcutaneous or intravenous MPTP, either 1 or 3 times per week. Immediately after MPTP injection, the minipigs remained in a corner and exhibited reduced trajectory. In addition, the total distance travelled, number of zone transitions, and velocity were greatly reduced at every MPTP administration in all the minipigs, accompanying to increased resting time. However, the MPTP-induced symptoms were reversed when MPTP administration was terminated. In conclusion, this automated video-tracking system was able to monitor long-term locomotor activity and differentiate detailed alterations in large animals. It has the advantages of being easy to use, higher resolution, less effort, and more delicate tracking. Additionally, as our method can be applied to the animals' home pen, no habituation is needed.

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“…[53,54] Bu skala: yüz ifadesi (0-3); dinlenme tremoru (0-3); eylem ya da niyet titremesi (0-3); duru (0-2); yürüyü (0-3); bradikinezi (0-4); denge koordinasyonu (0-3); üst ekstremite (0-3) ve alt ekstremite (0-3) kaba motor becerileri ve savunma gücü (0-2). [55] Bununla birlikte, PH'de MPTP tarafından uyarılmayan bazı temel de¤iiklikler vardır. Sonuç olarak, bu, PH'ye MPTP benzeri toksinlerin dahil edilmesine dair bazı üpheler do¤urmutur.…”

Section: Farelerunclassified

1-metil-4-fenil-1,2,3,6-tetrahidropiridinin (MPTP) Parkinson hastalığı üzerindeki etkileri

Akbulut

Köylüoğlu

Erbaş

2019

FNG & Demiroğlu Bilim Tıp Dergisi

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Parkinson's disease is a chronic movement disorder seen frequently in adults and caused by the destruction of dopaminergic neurons. Its symptoms are tremor, rigidity, balance disorder, and bradykinesia. The current medications of the disease cure the symptoms; none of them stops neurodegeneration. Various modellings are performed on experimental animals for Parkinson's disease research. The main substance used in these modellings is 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a synthetic toxin. MPTP is a neurotoxic agent that appeared unintentionally during the production of illicit drugs. MPTP converts to 1-methyl-4-phenyl-4-propionoxypiperidine in the body. This substance produces most of the biochemical, pathological, and clinical features similar to Parkinson's disease in an acute and irreversible way and this experimental Parkinson model leads many researchers. In this review, we discussed MPTP's discovery, metabolism, neurodegeneration mechanisms, and use in treatment in light of the literature.

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A non-human primate model for stable chronic Parkinson’s disease induced by MPTP administration based on individual behavioral quantification

Cited by 34 publications

References 44 publications

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

A pilot study on assessment of locomotor behavior using a video tracking system in minipigs

1-metil-4-fenil-1,2,3,6-tetrahidropiridinin (MPTP) Parkinson hastalığı üzerindeki etkileri

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