Abstract
Planaria are the simplest organisms with bilateral symmetry and a central nervous system (CNS) with cephalization; therefore, they could be useful as model organisms to investigate mechanistic aspects of parkinsonism and to screen potential therapeutic agents. Taking advantage of the organism’s anti-tropism towards light, we measured a significantly reduced locomotor velocity in planaria after exposure to 3-iodo-l-tyrosine, an inhibitor of tyrosine hydroxylase that is an enzyme catalyzing the first and rate-limiting step in the biosynthesis of catecholamines. A simple semi-automatic assay using videotaped experiments and subsequent evaluation by tracking software was also implemented to increase throughput. The dopaminergic regulation of locomotor velocity was confirmed by bromocriptine, a drug whose mechanisms of action to treat Parkinson’s disease is believed to be through the stimulation of nerves that control movement.
Highlights
Despite the paradigm shift toward target-focused strategies, phenotypic screening has resulted in the majority of drug discoveries even very recently [1]
We considered MIT to induce planarian parkinsonism that would be manifested through compromised movement
We reasoned that, taking advantage of the well-known anti-tropism of planarians to light, the velocity of movement away from a light source could be used as a novel behavioral test allowing for expedited assays performed simultaneously on multiple experimental subjects
Summary
Despite the paradigm shift toward target-focused strategies, phenotypic screening has resulted in the majority of drug discoveries even very recently [1]. Planaria respond to dopaminergic agents such as dopamine (DA) agonists/antagonists and neuronal DA reuptake inhibitors (e.g., cocaine) with characteristic behaviors or changes in locomotor activity [8,9]. The latter has been assessed quantitatively (9), and a computerized image analysis-based method to track and evaluate locomotion phenotype of planarians has been reported recently [10]. A model for parkinsonism to enable simple, rapid and inexpensive testing in a living system would be an attractive approach to screen compounds for potential neuroprotective activities. Paradigm is intended for an expedited testing of agents that would potentially preserve dopaminergic nerve functions
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