Potential of a planarian model to study certain aspects of anti-Parkinsonism drugs

Abstract

We previously created and investigated a planarian model for the study of drug action, abuse, physical dependence, receptor affinity, the toxicity of heavy metals in wastewater, and seizures. For the present pilot study, we investigated the possibility that this model might be useful for studying certain aspects of drugs used in treatment of Parkinson disease. For the first step, we were interested in finding an in vivo metric for the inhibition of L-DOPA by an inhibitor of DOPA decarboxylase. The direct clinical relevance of the endpoint was of secondary concern during this preliminary phase of model development. Two metrics were explored: L-DOPA-induced inhibition of motility (locomotor velocity) and dopamine-mediated toxicity, which was quantified using a Kaplan-Meier survival curve. L-DOPA produced both dose-and timerelated toxicity. The water-soluble DOPA decarboxylase inhibitor benserazide dose-dependently inhibited the effect of L-DOPA, as manifested by a leftward shift in the Kaplan-Meier curve. Additional work was initiated using the more sensitive and a graded metric of spontaneous locomotor velocity. The encouraging results of this pilot study suggest that: 1) planarians contain DOPA decarboxylase or an equivalent enzyme, and 2) the planarian model might be useful for the study of certain aspects of anti-Parkinsonism pharmacotherapy.

An Exploratory Evaluation of Tyrosine Hydroxylase Inhibition in Planaria as a Model for Parkinsonism

“…Planaria have been used as a model organism to study dopaminergic neurodegeneration and neuroregeneration [ 4 , 5 , 13 ], as well as neurotoxicity of anti-PD pharmacotherapy [ 14 ]. The pharmacological approach to induce planarian parkinsonism has relied on dopaminergic neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine [ 15 , 16 ].…”

Planarians Customize Their Stem Cell Responses Following Genotoxic Stress as a Function of Exposure Time and Regenerative State

“…In the planarian Schmidtea mediterranea, a large pool of adult pluripotent stem cells underlies an extensive regenerative capacity (Aboobaker, 2011;Gentile et al, 2011;Zhu and Pearson, 2016). Being a well-established stem cell model, it recently gained interest as a tool to investigate modes of action of toxicologically relevant compounds such as nanoparticles, neurotoxic drugs and carcinogenic compounds (Gentile et al, 2011;Hagstrom et al, 2015;Raffa et al, 2013;Salvetti et al, 2015). Their stem cell dynamics can be monitored in vivo, making these planarians extremely suitable to study responses of pluripotent stem cells to chemically-induced stressors in a realistic setting.…”

Toxicity profiles and solvent–toxicant interference in the planarian Schmidtea mediterranea after dimethylsulfoxide (DMSO) exposure

“…Planarians are considered as a model organism for neurotoxicological research (Best and Morita, 1991;Grebe and Schaeffer, 1991;Pagan et al, 2006;Raffa and Scott, 2008;Yuan et al, 2012;Tsushima et al, 2012;Raffa et al, 2013). They possess a well-organized nervous system, including many of the same neuroactive compounds as vertebrates and, together with their extensive repertoire of behaviour, they are suitable organisms for the study of neuronal effects of toxic substances.…”