Exploring the Role of PANNEXIN1A in an Acute Experimental Model of Parkinson's Disease

In the nervous system Pannexin1 channels are major ATP and glutamate release sites. The channels are implicated in neurodegenerative disorders including Parkinson’s disease, but the underlying mechanisms remain unclear. Here, an interdisciplinary approach tested roles of the mammalian Pannexin1 ortholog Pannexin1a in a zebrafish model of MPTP-induced early stages of Parkinson’s disease at molecular, systems, and behavioral levels. The short-term treatment of wild-type TL and gene-edited Panx1a-KO larvae caused metabolic stress, regulated inflammatory pathways, and reduced ATP production. Local field potentials recorded from three regions of the ascending visual pathway showed complex changes in the beta- and gamma-band power and in the coherence between these regions. MPTP treatment produced significantly impaired movements which were partially rescued by targeting the NLRP3 inflammasome. The main findings of this research provide evidence that Panx1a serves a neuroprotective role in an acute MPTP model of Parkinson's disease.