Purinergic Receptor P2Y2 Regulates Neurogenesis and Functional Recovery Following Spinal Cord Injury in Zebrafish

In contrast to mammals, adult zebrafish (Danio rerio) undergo neuronal regeneration following spinal cord injury (SCI), thereby allowing successful functional recovery. The adaptive regenerative response to SCI in zebrafish includes injury-induced proliferation of ependymal radial glial cells (ERGs) and neurogenesis. The molecular mechanisms underlying injury-induced neurogenesis in "regenerative" species, such as zebrafish, have not been fully elucidated and are an area of great interest. In mammals, the purinergic receptor P2Y2 has been shown to mediate NSC proliferation and neurogenesis, but its potential role following SCI or in zebrafish is unknown. Here, we found that P2Y2 is dysregulated following SCI in adult zebrafish, and pharmacological inhibition decreased swim capacity 2 weeks after injury. While P2Y2 was expressed on actively proliferating ERGs, antagonism of this receptor did not affect their proliferation levels. However, P2Y2 inhibition did attenuate SCI-induced neurogenesis and is strongly expressed by immature and mature neurons in adult zebrafish. Overall, P2Y2 serves as a pro-neurogenic factor during injury-induced neurogenesis and contributes to the recovery of swimming behavior in adult zebrafish.