1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Treated Adult Zebrafish as a Model for Parkinson’s Disease

Abstract

Dopamine (DA) is a neuroprotective catecholamine and neurotransmitter that works to regulate cognitive functions (Channer et al., 2023). Patients affected by Parkinson’s Disease (PD) experience a loss of dopaminergic neurons, lower levels of DA, and downregulated neural DA production. This leads to cognitive and physical decline that is the hallmark of PD. Currently, no cure exists for this prevalent neurodegenerative disease.Danio rerio, or zebrafish, have become an increasingly popular disease model used in PD pharmaceutical development. This model still requires extensive development to better characterize which PD features are adequately represented. Furthermore, the great majority of PD zebrafish models have been performed by treating embryos, which may not be relevant towards age-related human PD development. As an improvement, matureD. rerio(18 months) were treated with the neurotoxic prodrug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) through intraperitoneal injection to induce Parkinsonianism. Behavioral analysis confirmed the disparity in movement between saline-injected control and the MPTP experimental group, in which swim distance and speed were significantly lowered seven days after MPTP injection. Simultaneously, cognitive decline was apparent in MPTP zebrafish compared to control, demonstrated by decreased alternation in a y-maze. RT-qPCR confirmed trends consistent with downregulation in Parkinsonian genetic markers, specifically DA transporter (DAT), MAO-B, PINK1. In summary, mature zebrafish injected with MPTP present with similar movement and cognitive decline as compared to human disease. Despite its benefits, this model does not appear to recapitulate full pathophysiology of the disease with the full profile of expected gene downregulation. Because of this, it is important that researchers looking for pharmacological interventions for PD only use this zebrafish model when targeting the human-relevant PD symptoms and causes that are represented.