1. Applying the RatWalker System for Gait Analysis in a Genetic Rat Model of Parkinson's Disease
- Author
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Benjamin G. Lamberty, Howard S. Fox, Kelly L. Stauch, Kelsey N. Dyball, Steven Totusek, Trey Farmer, and Mohannad A. Almikhlafi
- Subjects
Male ,medicine.medical_specialty ,Parkinson's disease ,General Chemical Engineering ,Ubiquitin-Protein Ligases ,Video Recording ,Substantia nigra ,PINK1 ,Gene mutation ,Parkin ,General Biochemistry, Genetics and Molecular Biology ,Gene Knockout Techniques ,Mice ,Internal medicine ,Spectroscopy, Fourier Transform Infrared ,medicine ,Animals ,Humans ,Gait ,General Immunology and Microbiology ,Pars compacta ,business.industry ,General Neuroscience ,Dopaminergic Neurons ,Neurodegeneration ,Dopaminergic ,Parkinson Disease ,medicine.disease ,nervous system diseases ,Rats ,Substantia Nigra ,Disease Models, Animal ,Endocrinology ,business ,Gait Analysis - Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta. Gait abnormalities, including decreased arm swing, slower walking speed, and shorter steps are common in PD patients and appear early in the course of disease. Thus, the quantification of motor patterns in animal models of PD will be important for phenotypic characterization during disease course and upon therapeutic treatment. Most cases of PD are idiopathic; however, the identification of hereditary forms of PD uncovered gene mutations and variants, such as loss-of-function mutations in Pink1 and Parkin, two proteins involved in mitochondrial quality control that could be harnessed to create animal models. While mice are resistant to neurodegeneration upon loss of Pink1 and Parkin (single and combined deletion), in rats, Pink1 but not Parkin deficiency leads to nigral DA neuron loss and motor impairment. Here, we report the utility of FTIR imaging to uncover gait changes in freely walking young (2 months of age) male rats with combined loss of Pink1 and Parkin prior to the development of gross visually apparent motor abnormality as these rats age (observed at 4-6 months), characterized by hindlimb dragging as previously reported in Pink1 knockout (KO) rats.
- Published
- 2021