Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Jog, Mandar S.

2nd Supervisor

Rajakumar, Nagalingam

Co-Supervisor

Abstract

Loss of dopamine in Parkinson’s disease is associated with glutamatergic hyperactivity of the subthalamic nucleus. Pharmacological and electrical therapies aimed to suppress this overactivity favourably alleviate parkinsonian motor symptoms. No study has explored the potential of botulinum neurotoxin A in the central nervous system beyond cholinergic blockage despite evidence of its ability to inhibit glutamate release. Thus, the present study investigates the effect of selective suppression of hyperactive glutamatergic input from the subthalamic nucleus to the entopeduncular nucleus by botulinum neurotoxin A in a parkinsonian model. Unilateral 6-hydroxydopamine lesioned rodents received microinfusions of botulinum neurotoxin A or vehicle into the ipsilateral entopeduncular nucleus, and their mobility was assessed using the CatWalk apparatus. Administration of a single dose of botulinum neurotoxin A (0.5 ng) significantly improved the rotational asymmetry and dynamic gait abnormalities, suggesting a potential use of intracerebral botulinum neurotoxin A to produce effective neuromodulation in the parkinsonian brain.

Available for download on Monday, August 31, 2020

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