Method Article
Here we describe the RatWalker system, built by redesigning the MouseWalker apparatus to accommodate for the increased size and weight of rats. This system uses frustrated total internal reflection (FTIR), high-speed video capture, and open-access analysis software to track and quantify gait parameters.
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.
PD, the most common age-related neurodegenerative movement disorder, is caused by the loss of DA neurons in the substantia nigra pars compacta. This loss of nigral DA neurons and the DA inputs into the striatum lead to the observed motor function impairments seen in patients with PD1,2. The defining motor characteristics of patients with PD, known collectively as Parkinsonism, include rigidity, resting tremor, bradykinesia, postural instability, and micrographia3. Furthermore, gait disturbances, which are common in PD patients, appear early in the course of disease1
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All animal studies were approved by the University of Nebraska Medical Center Institutional Animal Care and Use Committee (IACUC).
1. Gait apparatus
NOTE: Modeled from the MouseWalker14, the RatWalker was designed with dimensions in proportion to the difference in step length between rats and mice. It consists of a side illumination backlight, walkway enclosure, optical waveguide walkway, mirror, and camera (Figure S1). LED strips, oriented in a staggered position, were used on each side of the walkway and backlight waveguides to accommodate the extra material. The materials....
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Rat Colony Maintenance
The generation and characterization of Pink1 and Parkin single KO rats has been described previously22. The Pink1 and Parkin single KO rats were obtained from SAGE Labs (and now available from Envigo). DKO rats were generated by crossing Pink1-/- rats with Parkin-/- rats to obtain Pink1+/-/Parkin+/- rats, which were interbred to obtain Pink1-/-/Parkin-/- .......
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Gait disturbances, including decreased arm swing, slower walking speed, and shorter steps, are a defining feature of PD, and occur early during disease course1,5. Several methods have been developed over the years to observe and record footfalls for gait analysis in rodent models of PD, with manual techniques for quantifying footfall position leading to automated approaches that are more sensitive and capable of capturing dynamic parameters. Some static approache.......
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The authors declare no competing financial interests.
KS and HF thank the Michael J Fox Foundation for Parkinson's Research for support of their work on Parkinson's disease.
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| Name | Company | Catalog Number | Comments |
|---|---|---|---|
| Aluminum | |||
| 1.5” Aluminum Angle (1/8” - 6063) | Dimensions: 8' Qty: 8 | ||
| 1” Aluminum Square Tube (1/16” - 6063) | Dimensions: 8' Qty: 4 | ||
| 32 Gauge Aluminum Sheet | Dimensions: 10' Qty: 1 | ||
| 1” Aluminum Tube (1/8” - 6063) | Dimensions: 8' Qty: 1 | ||
| Acrylic | |||
| 7/32” Clear Acrylic Sheet | Dimensions: 4'x8' Qty: 2 | ||
| 1/8” White Acrylic Sheet 55% (2447) | Dimensions: 4'x8' Qty: 1 | ||
| Mirror | |||
| 7/32” Glass Mirror | Dimensions: 60"x12" Qty: 1 | ||
| LED | |||
| 5050 LED Tape Light (Green) | Dimensions: 16.4' Qty: 1 | ||
| 5050 LED Tape Light (Red) | Dimensions: 16.4' Qty: 1 | ||
| Camera | |||
| GoPro Hero 6 Black | Qty: 1 | ||
| Tripod | Dimensions: 57" Qty: 1 |
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