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A novel biomechanical analysis of gait changes in the MPTP mouse model of Parkinson's disease.

Geldenhuys WJ, Guseman TL, Pienaar IS, Dluzen DE, Young JW - PeerJ (2015)

Bottom Line: However, most existing behavioral assays currently applied to such animal models fail to adequately detect and subsequently quantify the subtle changes associated with the progressive stages of PD.Analyses revealed shuffling behaviors consistent with the gait symptoms of advanced PD in humans.Our findings indicate that this method is a useful means by which to easily and economically screen preclinical therapeutic compounds for protecting against or reversing neuropathology associated with PD neurodegeneration.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University (NEOMED) , Rootstown, OH , USA.

ABSTRACT
Parkinson's disease (PD) is an age-associated neurodegenerative disorder hallmarked by a loss of mesencephalic dopaminergic neurons. Accurate recapitulation of the PD movement phenotype in animal models of the disease is critical for understanding disease etiology and developing novel therapeutic treatments. However, most existing behavioral assays currently applied to such animal models fail to adequately detect and subsequently quantify the subtle changes associated with the progressive stages of PD. In this study, we used a video-based analysis system to develop and validate a novel protocol for tracking locomotor performance in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We anticipated that (1) treated mice should use slower, shorter, and less frequent strides and (2) that gait deficits should monotonically increase following MPTP administration, as the effects of neurodegeneration become manifest. Video-based biomechanical analyses, utilizing behavioral measures motivated by the comparative biomechanics literature, were used to quantify gait dynamics over a seven-day period following MPTP treatment. Analyses revealed shuffling behaviors consistent with the gait symptoms of advanced PD in humans. Here we also document dramatic gender-based differences in locomotor performance during the progression of the MPTP-induced lesion, despite male and female mice showing similar losses of striatal dopaminergic cells following MPTP administration. Whereas female mice appeared to be protected against gait deficits, males showed multiple changes in gait kinematics, consistent with the loss of locomotor agility and stability. Overall, these data show that the novel video analysis protocol presented here is a robust method capable of detecting subtle changes in gait biomechanics in a mouse model of PD. Our findings indicate that this method is a useful means by which to easily and economically screen preclinical therapeutic compounds for protecting against or reversing neuropathology associated with PD neurodegeneration.

No MeSH data available.


Related in: MedlinePlus

Sample frame from high-speed video analyses of mouse locomotion.Video analysis software was used to digitize the two-dimensional position of the nose and tail base during the pass down the trackway. A pair of mirrors angled at 45° to the sagittal plane allowed for capturing touchdown and lift-off events over complete gait cycles.
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fig-1: Sample frame from high-speed video analyses of mouse locomotion.Video analysis software was used to digitize the two-dimensional position of the nose and tail base during the pass down the trackway. A pair of mirrors angled at 45° to the sagittal plane allowed for capturing touchdown and lift-off events over complete gait cycles.

Mentions: The mice were made to run along a white wooden trackway (41.75 cm long, 4 cm wide) into a dark box located at the terminal end of the track. The trackway was placed on a laboratory bench top, approximately 1 m off the ground. Mice were filmed with a high-speed digital camera (MotionScope Model PCI 1000s; Redlake MASD Inc., San Diego, California, USA) placed overhead to allow for a dorsal view of the mouse running along the trackway. Videos were recorded at 200 frames per second (fps) with a 1/2,000 shutter speed. The trackway was illuminated with a 250-watt quartz light (Lowel-Light Manufacturing Inc., Brooklyn, New York, USA) to provide adequate depth of field. On either side of the runway, mirrors were placed at 45° angles to the sagittal plane to provide complete views of the footfalls of each limb during locomotion (Fig. 1). We recorded 15–25 strides per mouse per day. All testing took place between 10AM and 2PM, during the active (dark) phase of these nocturnal animals.


A novel biomechanical analysis of gait changes in the MPTP mouse model of Parkinson's disease.

Geldenhuys WJ, Guseman TL, Pienaar IS, Dluzen DE, Young JW - PeerJ (2015)

Sample frame from high-speed video analyses of mouse locomotion.Video analysis software was used to digitize the two-dimensional position of the nose and tail base during the pass down the trackway. A pair of mirrors angled at 45° to the sagittal plane allowed for capturing touchdown and lift-off events over complete gait cycles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4558067&req=5

fig-1: Sample frame from high-speed video analyses of mouse locomotion.Video analysis software was used to digitize the two-dimensional position of the nose and tail base during the pass down the trackway. A pair of mirrors angled at 45° to the sagittal plane allowed for capturing touchdown and lift-off events over complete gait cycles.
Mentions: The mice were made to run along a white wooden trackway (41.75 cm long, 4 cm wide) into a dark box located at the terminal end of the track. The trackway was placed on a laboratory bench top, approximately 1 m off the ground. Mice were filmed with a high-speed digital camera (MotionScope Model PCI 1000s; Redlake MASD Inc., San Diego, California, USA) placed overhead to allow for a dorsal view of the mouse running along the trackway. Videos were recorded at 200 frames per second (fps) with a 1/2,000 shutter speed. The trackway was illuminated with a 250-watt quartz light (Lowel-Light Manufacturing Inc., Brooklyn, New York, USA) to provide adequate depth of field. On either side of the runway, mirrors were placed at 45° angles to the sagittal plane to provide complete views of the footfalls of each limb during locomotion (Fig. 1). We recorded 15–25 strides per mouse per day. All testing took place between 10AM and 2PM, during the active (dark) phase of these nocturnal animals.

Bottom Line: However, most existing behavioral assays currently applied to such animal models fail to adequately detect and subsequently quantify the subtle changes associated with the progressive stages of PD.Analyses revealed shuffling behaviors consistent with the gait symptoms of advanced PD in humans.Our findings indicate that this method is a useful means by which to easily and economically screen preclinical therapeutic compounds for protecting against or reversing neuropathology associated with PD neurodegeneration.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University (NEOMED) , Rootstown, OH , USA.

ABSTRACT
Parkinson's disease (PD) is an age-associated neurodegenerative disorder hallmarked by a loss of mesencephalic dopaminergic neurons. Accurate recapitulation of the PD movement phenotype in animal models of the disease is critical for understanding disease etiology and developing novel therapeutic treatments. However, most existing behavioral assays currently applied to such animal models fail to adequately detect and subsequently quantify the subtle changes associated with the progressive stages of PD. In this study, we used a video-based analysis system to develop and validate a novel protocol for tracking locomotor performance in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We anticipated that (1) treated mice should use slower, shorter, and less frequent strides and (2) that gait deficits should monotonically increase following MPTP administration, as the effects of neurodegeneration become manifest. Video-based biomechanical analyses, utilizing behavioral measures motivated by the comparative biomechanics literature, were used to quantify gait dynamics over a seven-day period following MPTP treatment. Analyses revealed shuffling behaviors consistent with the gait symptoms of advanced PD in humans. Here we also document dramatic gender-based differences in locomotor performance during the progression of the MPTP-induced lesion, despite male and female mice showing similar losses of striatal dopaminergic cells following MPTP administration. Whereas female mice appeared to be protected against gait deficits, males showed multiple changes in gait kinematics, consistent with the loss of locomotor agility and stability. Overall, these data show that the novel video analysis protocol presented here is a robust method capable of detecting subtle changes in gait biomechanics in a mouse model of PD. Our findings indicate that this method is a useful means by which to easily and economically screen preclinical therapeutic compounds for protecting against or reversing neuropathology associated with PD neurodegeneration.

No MeSH data available.


Related in: MedlinePlus