Abstract Title

Catwalk analysis: a novel approach to profiling age differences in gait

Presenter Name

Thomas Mock

RAD Assignment Number

1524

Abstract

The Catwalk is a validated video-based gait analysis tool for quantitative analysis of both static and dynamic differences in rodent gait and weight-bearing. The Catwalk has been used to analyze disease states such as stroke, sciatic nerve crush and osteoarthritis, however age-related changes in rodent gait are not well characterized. Motor impairments have been associated with dysregulated cellular redox state, namely levels of reduced to oxidized glutathione. Glutamate-cysteine ligase modifier (gclm) is a key enzyme sub-unit in the production of glutathione (GSH), and knocking it out reduces GSH levels by 85%. The gclm -/- mice are a potential model of accelerated aging and should develop impairments earlier than wild-type mice. Our hypothesis was that gait measures would decrease with advanced age and that impairments would occur sooner in gclm -/- mice.

Wild-type (wt) and gclm-/- male and female mice were tested at 4, 10 or 17 months of age (n = 8-11/group). All testing was done in pitch black and a camera below the illuminated transparent platform captured each paw print as animals walked across the platform. Paw prints were automatically labeled according to left/right or front/hind then manually checked. A criterion for a good run was set as less than 60% speed variation within the run and less than 10% speed variation between runs. Two to five runs per animal were used for two-way analyses of variance of the dependent measures collected using Genotype and Age as in between factors. The dependent measures were gait speed (SP), front and hind base of support (BoSf, BoSh), front and hind stride length (SLf, SLh), front and hind stride speed (SSf, SSh), front and hind step cycle (SCf, SCh), and front and hind duty cycle (DCf, DCh).

Gait speed decreased with age in both genotypes. BoS decreased in front legs and increased in hind legs in both genotypes. Stride length was decreased with age, and more prominently in the gclm-/-, while stride speed decreased with age and was higher in gclm-/-. Step cycles increased with age in the wt but not in the gclm-/-. Duty cycles increased with age, especially in the gclm-/-.

These preliminary data suggest that age leads to measurable changes in mouse gait and that GSH dysregulation had only minor effects on gait. In conclusion, Catwalk analysis is sufficiently sensitive to measure subtle age-related changes in gait across several age-ranges, and can be added to the current battery of behavioral tests.

Presentation Type

Oral

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Catwalk analysis: a novel approach to profiling age differences in gait

The Catwalk is a validated video-based gait analysis tool for quantitative analysis of both static and dynamic differences in rodent gait and weight-bearing. The Catwalk has been used to analyze disease states such as stroke, sciatic nerve crush and osteoarthritis, however age-related changes in rodent gait are not well characterized. Motor impairments have been associated with dysregulated cellular redox state, namely levels of reduced to oxidized glutathione. Glutamate-cysteine ligase modifier (gclm) is a key enzyme sub-unit in the production of glutathione (GSH), and knocking it out reduces GSH levels by 85%. The gclm -/- mice are a potential model of accelerated aging and should develop impairments earlier than wild-type mice. Our hypothesis was that gait measures would decrease with advanced age and that impairments would occur sooner in gclm -/- mice.

Wild-type (wt) and gclm-/- male and female mice were tested at 4, 10 or 17 months of age (n = 8-11/group). All testing was done in pitch black and a camera below the illuminated transparent platform captured each paw print as animals walked across the platform. Paw prints were automatically labeled according to left/right or front/hind then manually checked. A criterion for a good run was set as less than 60% speed variation within the run and less than 10% speed variation between runs. Two to five runs per animal were used for two-way analyses of variance of the dependent measures collected using Genotype and Age as in between factors. The dependent measures were gait speed (SP), front and hind base of support (BoSf, BoSh), front and hind stride length (SLf, SLh), front and hind stride speed (SSf, SSh), front and hind step cycle (SCf, SCh), and front and hind duty cycle (DCf, DCh).

Gait speed decreased with age in both genotypes. BoS decreased in front legs and increased in hind legs in both genotypes. Stride length was decreased with age, and more prominently in the gclm-/-, while stride speed decreased with age and was higher in gclm-/-. Step cycles increased with age in the wt but not in the gclm-/-. Duty cycles increased with age, especially in the gclm-/-.

These preliminary data suggest that age leads to measurable changes in mouse gait and that GSH dysregulation had only minor effects on gait. In conclusion, Catwalk analysis is sufficiently sensitive to measure subtle age-related changes in gait across several age-ranges, and can be added to the current battery of behavioral tests.