Loss of Panx1 function in zebrafish alters motor behavior in a lab‐on‐chip model of Parkinson's disease

Abstract

AbstractPannexin 1 (Panx1) forms ATP‐permeable membrane channels that play roles in purinergic signaling in the nervous system. A link between Panx1 activity and neurodegenerative disorders including Parkinson's disease (PD) has been suggested, but experimental evidence is limited. Here, a zebrafish model of PD was produced by exposing panx1a+/+ and panx1a−/− zebrafish larvae to 6‐hydroxydopamine (6‐OHDA). Electrical stimulation in a microfluidic chip and quantitative real‐time‐qPCR of zebrafish larvae tested the role of Panx1 in both pathological and normal conditions. After 72‐h treatment with 6‐OHDA, the electric‐induced locomotor activity of 5 days post fertilization (5dpf) panx1a+/+ larvae were reduced, while the stimulus did not affect locomotor activity of age‐matched panx1a−/− larvae. A RT‐qPCR analysis showed an increase in the expression of genes that are functionally related to dopaminergic signaling, like the tyrosine hydroxylase (th2) and the leucine‐rich repeat kinase 2 (lrrk2). Extending the 6‐OHDA treatment duration to 120 h caused a significant reduction in the locomotor response of 7dpf panx1a−/− larvae compared to the untreated panx1a−/− group. The RT‐qPCR data showed a reduced expression of dopaminergic signaling genes in both genotypes. It was concluded that the absence of Panx1a channels compromised dopaminergic signaling in 6‐OHDA‐treated zebrafish larvae and that the increase in the expression of dopaminergic genes was transient, most likely due to a compensatory upregulation. We propose that zebrafish Panx1a models offer opportunities to shed light on PD's physiological and molecular basis. Panx1a might play a role on the progression of PD, and therefore deserves further investigation.