Overexpression of Reticulon 3 Enhances CNS Axon Regeneration and Functional Recovery after Traumatic Injury

This research investigates Reticulon 3 (RTN3)'s role in helping nerve cells regrow after spinal cord and optic nerve injuries. Prior research has shown that CNS neurons are generally incapable of regenerating their axons after injury. The study found that when RTN3 is increased in nerve cells, it encourages the growth of nerve fibers and helps restore function after injury. Overexpression of RTN3 promoted disinhibited DRGN neurite outgrowth in vitro and dorsal column axon regeneration/sprouting and electrophysiological, sensory and locomotor functional recovery after injury in vivo. The positive effects of RTN3 depend on a protein called protrudin. These results demonstrate that RTN3 enhances neurite outgrowth/axon regeneration in a protrudin-dependent manner after both spinal cord and optic nerve injury.

• 1
  RTN3 expression is higher in nerve cells that are regenerating after injury. We used qRT-PCR to demonstrate that RTN3 levels were upregulated by 4.2 ± 0.05- and 6.2 ± 0.04-fold in regenerating SN and pSN + DC DRGN compared to those harvested after DC injury
• 2
  Increasing RTN3 levels promotes nerve fiber growth in lab-grown nerve cells and after spinal cord injury in rats. Overexpression of RTN3 disinhibited DRGN neurite outgrowth such that DRGN were significantly longer in length
• 3
  The beneficial effects of RTN3 on nerve regeneration require the presence of protrudin. Knockdown of protrudin, however, ablated RTN3-enhanced neurite outgrowth/axon regeneration in vitro and in vivo.