title: Spinal axon regeneration induced by elevation of cyclic AMP.
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.
authors.affiliation: Biology Department, Hunter College, City University of New York, 695 Park Avenue, New York, NY 10021, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Qiu
authors.forename: Dongming
authors.initials: D
authors.lastname: Cai
authors.forename: Haining
authors.initials: H
authors.lastname: Dai
authors.forename: Marietta
authors.initials: M
authors.lastname: McAtee
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hoffman
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Bregman
authors.forename: Marie T
authors.initials: MT
authors.lastname: Filbin
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases