Spinal Axon Regeneration Induced by Elevation of Cyclic AMP

Neuron. 2002 Jun 13;34(6):895-903. doi: 10.1016/s0896-6273(02)00730-4.

Abstract

Myelin inhibitors, including MAG, are major impediments to CNS regeneration. However, CNS axons of DRGs regenerate if the peripheral branch of these neurons is lesioned first. We show that 1 day post-peripheral-lesion, DRG-cAMP levels triple and MAG/myelin no longer inhibit growth, an effect that is PKA dependent. By 1 week post-lesion, DRG-cAMP returns to control, but growth on MAG/myelin improves and is now PKA independent. Inhibiting PKA in vivo blocks the post-lesion growth on MAG/myelin at 1 day and attenuates it at 1 week. Alone, injection of db-cAMP into the DRG mimics completely a conditioning lesion as DRGs grow on MAG/myelin, initially, in a PKA-dependent manner that becomes PKA independent. Importantly, DRG injection of db-cAMP results in extensive regeneration of dorsal column axons lesioned 1 week later. These results may be relevant to developing therapies for spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / enzymology
  • Axons / physiology*
  • Bucladesine / pharmacology
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / biosynthesis*
  • Cyclic AMP / physiology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / physiology*
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Bucladesine
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases