Loss of Panx1 Function in Zebrafish Alters Motor Behavior in a
Lab-on-Chip Model of Parkinson's Disease
Abstract
Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play
essential roles in purinergic signaling in the nervous system. Several
studies suggest a link between Panx1-based channels activity and
neurodegenerative disorders including Parkinson’s disease (PD), but
experimental evidence is limited. Here, we applied behavioral and
molecular screening of zebrafish larvae to examine the role of Panx1 in
both pathological and normal conditions, using electrical stimulation in
a microfluidic chip and RT-qPCR. A zebrafish model of PD was produced by
exposing wildtype (panx1a+/+) and Panx1a knock-out (panx1a-/-) zebrafish
larvae to 250µM 6-hydroxydopamine (6-OHDA). After 72hrs treatment with
6-OHDA a reduced electric-induced locomotor activity was observed in 5
days post fertilization (dpf) panx1a+/+ larvae. The 5dpf panx1a-/-
larvae were not different from affected. The RT-qPCR data showed a
reduction in tyrosine hydroxylase (TH) expression level in both
panx1a+/+ and panx1a-/- groups. However, TH expression of 6-OHDA exposed
panx1a-/- larvae was not decreased when compared to untreated mutants.
Extending 6-OHDA treatment duration to 120hrs caused a significant
reduction in the locomotor response of 7dpf panx1a-/- larvae when
compared to the untreated panx1a-/- group. The RT-qPCR data also
confirmed a significant decrease in TH expression levels after 120hrs
treatments with 6-OHDA for both genotypes. Our results suggest that the
absence of Panx1a channels compromised dopaminergic signaling in
6-OHDA-treated zebrafish larvae. We here propose that zebrafish Panx1a
models offer great opportunities to shed light on the physiological and
molecular basis of PD. Panx1a might play a preventive role on PD
progression, and therefore deserves further investigation