Paraquat and 6-hydroxydopamine modulate nucleotide and nucleoside catabolism in zebrafish

Parkinson's disease (PD) is considered the second most common neurodegenerative disease in the world. Animal models based on exposure to Paraquat (Pq) or 6-hydroxydopamine (6-OHDA) have been used to better understand and find new therapies for PD. Purinergic signaling has emerged as a pivotal factor in the progression of PD. We assessed the influence of Pq or 6-OHDA on ATP metabolism as well as nucleotide and nucleoside-metabolizing enzyme activities and gene expression in adult zebrafish brain. Adult zebrafish were injected i.p. with saline (vehicle) or Pq (10 or 20 mg/kg) with two days of intervals to complete a total of six doses. For 6-OHDA treatment, zebrafish received one i.p. injection with saline (vehicle) or 6-OHDA (25 or 50 mg/kg). Immediately after the treatments, ATP metabolism was evaluated in zebrafish brain. There were no alterations in extracellular nucleotide (ATP, ADP, and AMP) levels after Pq treatment. A decrease in extracellular adenosine catabolism was seen when compared to the control group. In 6-OHDA-treated fish, there were no changes in ATP levels. However, ADP levels showed differences after 6-OHDA exposure and AMP levels decreased in both doses (25 and 50 mg/kg), while adenosine levels increased when compared to the controls. Also, both treatments increased extracellular inosine levels, a potential candidate for PD treatment. The results demonstrated changes in ADA expression, with a significant increase in ADAasi mRNA levels after 6-OHDA exposure in zebrafish brain. These findings reinforce the involvement of purinergic signaling in PD and provide relevant insights about novel therapeutical approaches.