Identification of antiparkinsonian drugs in the 6-hydroxydopamine zebrafish model

Publication date: Available online 28 November 2019Source: Pharmacology Biochemistry and BehaviorAuthor(s): Rita L. Vaz, Sara Sousa, Diana Chapela, Herma C. van der Linde, Rob Willemsen, Ana D. Correia, Tiago F. Outeiro, Nuno D. AfonsoAbstractParkinson's disease (PD) is known as a movement disorder due to characteristic motor features. Existing therapies for PD are only symptomatic, and their efficacy decreases as disease progresses. Zebrafish, a vertebrate in which parkinsonism has been modelled, offers unique features for the identification of molecules with antiparkinsonian properties. Here, we developed a screening assay for the selection of neuroactive agents with antiparkinsonian potential. First, we performed a pharmacological validation of the phenotypes exhibited by the 6-hydroxydopamine zebrafish model, by testing the effects of known antiparkinsonian agents. These drugs were also tested for disease-modifying properties by whole mount immunohistochemistry to TH+ neurons and confocal microscopy in the dopaminergic diencephalic cluster of zebrafish. Next, we optimized a phenotypic screening using the 6-hydroxydopamine zebrafish model and tested 1600 FDA-approved bioactive drugs. We found that 6-hydroxydopamine-lesioned zebrafish larvae exhibit bradykinetic and dyskinetic-like behaviours that are rescued by the administration of levodopa, rasagiline, isradipine or amantadine. The rescue of dopaminergic cell loss by isradipine was also verified, through the observation ...
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research