Spinal axon regeneration induced by elevation of cyclic AMP

Jin Qiu, Dongming Cai, Haining Dai, Marietta McAtee, Paul N. Hoffman, Barbara S. Bregman, Marie T. Filbin

Research output: Contribution to journalArticlepeer-review

612 Scopus citations

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.

Original languageEnglish
Pages (from-to)895-903
Number of pages9
JournalNeuron
Volume34
Issue number6
DOIs
StatePublished - 13 Jun 2002
Externally publishedYes

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