Activation of A2A Receptor by PDRN Reduces Neuronal Damage and Stimulates WNT/β-CATENIN Driven Neurogenesis in Spinal Cord Injury

Spinal cord injury (SCI) leads to nerve cell loss and damage. Adenosine receptors, found on various brain cells, are being explored as drug targets. This study investigates PDRN, an adenosine receptor stimulator, in a mouse model of SCI, also examining its impact on the Wnt pathway, crucial for nerve cell development. Mice with induced SCI were treated with PDRN, with or without DMPX (an adenosine receptor blocker). The study found PDRN reduced tissue damage, improved motor skills, lowered pro-inflammatory markers, and boosted the Wnt pathway after SCI. These findings suggest PDRN's anti-inflammatory properties and its potential to promote nerve repair via adenosine receptor activation and Wnt pathway stimulation. PDRN might aid in axonal regeneration or neurogenesis after spinal cord injury.

• 1
  PDRN treatment significantly improved motor function in mice with SCI, as measured by the Basso mouse scale (BMS). The improvement was negated by the co-administration of DMPX, an adenosine receptor antagonist.
• 2
  PDRN administration significantly decreased the levels of pro-inflammatory cytokines IL-1β and TNF-α in SCI-treated animals, indicating an anti-inflammatory effect. PDRN also reduced neutrophil infiltration into the spinal cord tissue.
• 3
  PDRN modulated the Wnt signaling pathway by increasing the mRNA expression of Wnt3a and β-catenin, while reducing the expression of DKK-1, a Wnt inhibitor. DMPX abolished these effects of PDRN, confirming the involvement of A2A receptors.