Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Neuroscience

Supervisor

Jog, Mandar S

Affiliation

London Health Sciences Center

2nd Supervisor

Rajakumar, Nagalingam

Co-Supervisor

Abstract

Dopaminergic degeneration in Parkinson’s disease (PD) leads to altered functional activity within the basal ganglia (BG) circuitry, including hyperactivity of the subthalamic nucleus (STN). Treatments restoring the BG functional circuitry often result in improvements in parkinsonian symptoms in patients and animal models. A recent study from our laboratory identified that infusing botulinum toxin (BoNT-A) into the internal globus pallidus provided a transient restoration of motor asymmetry and goal-directed locomotion in a rat model of PD. We hypothesized that infusions of BoNT-A into the STN in a parkinsonian rat model will improve motor asymmetry and locomotor abnormalities. Infusions of BoNT-A into the ipsilateral STN in unilaterally 6-hydroxydopamine lesioned rats assessed in the apomorphine rotation task, rotarod, or CatWalk apparatus revealed a dose-dependent amelioration of pathological rotations, while failing to affect spontaneous locomotion. The present results suggest that spontaneous locomotion may not dependent on the integrity of the BG functional circuitry.

Summary for Lay Audience

In Parkinson’s disease dopaminergic cells die in the substantia nigra, a region part of the brains motor circuitry. This cell death leads to changes in the functional activity of this motor circuitry which leads to motor symptoms. Treatment options for Parkinson’s disease try to restore or alter the activity of this circuitry to improve motor symptoms. This study investigates the effects of a potential new treatment in a rat model of Parkinson’s disease. This new treatment involves injecting botulinum neurotoxin in a very small dose directly into the brain to alter the activity of the motor circuitry, which is impaired in disease, to more normal levels of activity. This study investigates the effects of various doses of botulinum toxin in the brain of a rat. This study will assess this treatments effect on drug-induced movement, forced movement, and voluntary movement. It was found that the two highest doses of botulinum toxin were successful in reducing pathological drug induced rotations, meaning that this treatment successfully changed the levels of activity in the brains motor circuitry to healthier levels. The rats did not develop impaired gait in this study, thus it is unknown whether this treatment would have improved a deficit in gait. The results are promising and the effects of this treatment on impaired gait need to be examined in a future study in animals with impaired walking.

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