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慢性帕金森病非人灵长类动物模型中的手部灵巧功能受损

Impaired Hand Dexterity Function in a Non-human Primate Model with Chronic Parkinson's Disease.

作者信息

Seo Jincheol, Won Jinyoung, Kim Keonwoo, Park Junghyung, Yeo Hyeon-Gu, Kim Yu Gyeong, Baek Seung Ho, Lee Hoonwon, Jeon Chang-Yeop, Choi Won Seok, Lee Sangil, Kim Ki Jin, Park Sung-Hyun, Son Yeonghoon, Jeong Kang Jin, Lim Kyung Seob, Kang Philyong, Lee Hwal-Yong, Son Hee-Chang, Huh Jae-Won, Kim Young-Hyun, Lee Dong-Seok, Lee Sang-Rae, Choi Ji-Woong, Lee Youngjeon

机构信息

National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea.

School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea.

出版信息

Exp Neurobiol. 2020 Oct 31;29(5):376-388. doi: 10.5607/en20040.

Abstract

Symptoms of Parkinson's disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

摘要

由多巴胺能神经元丧失引起的帕金森病(PD)症状伴有运动障碍,包括震颤、僵硬、运动迟缓及运动不能。患有帕金森病的非人灵长类动物(NHP)模型在帕金森病病理生理学和行为症状分析中起着至关重要的作用。由于手部灵巧功能受损会影响帕金森病患者的日常生活活动,因此对慢性帕金森病非人灵长类动物模型的手部灵巧功能进行研究至关重要。以前用于评估动物自发行为的传统评分量表由于主观性和被动性等因素而不够充分。因此,需要针对合适的仪器设计实验应用。在本研究中,我们旨在使用手部灵巧任务(HDT)对非人灵长类帕金森病模型的手部灵巧功能进行纵向评估。为了验证这一评估,我们在这些模型中使用多巴胺转运体的正电子发射断层扫描成像分析了帕金森震颤体征的变化和突触前多巴胺能神经元的功能。此外,我们发现HDT与多巴胺转运体(DAT)水平之间存在显著的负相关,但未发现局部偏差。与意向性震颤体征的相关性低于静止性震颤。总之,HDT评估可能反映了非人灵长类帕金森病模型的行为症状。此外,HDT被有效地用于通过实验区分意向性震颤与其他震颤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0ab/7649085/eac88c15cd12/EN-29-376-f1.jpg

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