Spinal Axon Regeneration Induced by Elevation of Cyclic AMP

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...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2002-06, Vol.34 (6), p.895-903
Main Authors: Qiu, Jin, Cai, Dongming, Dai, Haining, McAtee, Marietta, Hoffman, Paul N., Bregman, Barbara S., Filbin, Marie T.
Format: Article
Language:English
Subjects:
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
Kinases
Medical research
Nerve Regeneration - drug effects
Nerve Regeneration - physiology
Rats
Rats, Sprague-Dawley
Rodents
Spinal cord
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Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(02)00730-4