Quantitative evaluation of motor function before and after engraftment of dopaminergic neurons in a rat model of Parkinson's disease

Chieh-Sen Chuang,Fu-Chou Cheng,Chi-Fen Chuang,Chin-San Liu,Shan-Hui Hsu,Hong-Lin Su

doi:10.1186/1423-0127-17-9

Abstract

Although gait change is considered a useful indicator of severity in animal models of Parkinson's disease, systematic and extensive gait analysis in animal models of neurological deficits is not well established. The CatWalk-assisted automated gait analysis system provides a comprehensive way to assess a number of dynamic and static gait parameters simultaneously. In this study, we used the Catwalk system to investigate changes in gait parameters in adult rats with unilateral 6-OHDA-induced lesions and the rescue effect of dopaminergic neuron transplantation on gait function. Four weeks after 6-OHDA injection, the intensity and maximal area of contact were significantly decreased in the affected paws and the swing speed significantly decreased in all four paws. The relative distance between the hind paws also increased, suggesting that animals with unilateral 6-OHDA-induced lesions required all four paws to compensate for loss of balance function. At 8 weeks post-transplantation, engrafted dopaminergic neurons expressed tyrosine hydroxylase. In addition, the intensity, contact area, and swing speed of the four limbs increased and the distance between the hind paws decreased. Partial recovery of methamphetamine-induced rotational response was also noted.

Highlights

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease
The present study demonstrated that the CatWalk method is useful for analyzing gait changes in rats after unilateral 6OHDA lesioning and dopaminergic neuron grafting
Some of the dynamic and static parameters were altered in rats with 6-OHDA-induced lesions including paw contact pressure and area, velocity, and hindlimb support

Summary

Introduction

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The worldwide prevalence is estimated to be 200 per 100,000 population [1]. Common parkinsonian symptoms are rest tremor, bradykinesia, rigidity, and loss of postural reflexes [2]. Gait disturbances are one of the most common motor problems in Parkinson's disease. Patients with PD often present with a stooped posture and shuffling gait, decreased stride length and overall velocity, increased double-limb support, reduced foot clearance during swing phase, and increased cadence leading to the potential for falls [3,4,5]. Progressive gait disturbance combined with posture instability deprives patients of locomotor ability and activities of daily living [6].

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Conclusion