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 language | English (US) |
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Pages (from-to) | 895-903 |
Number of pages | 9 |
Journal | Neuron |
Volume | 34 |
Issue number | 6 |
DOIs | |
State | Published - Jun 13 2002 |
Externally published | Yes |
Bibliographical note
Funding Information:We thank Dr. Arthur McMorris and Dr. Anthony Weimelt for providing the cAMP antibody, Dr. Roger Persell for critically reading this manuscript, and Dr. Lloyd Williams for his assistance with the image analysis. This work was supported by grants from the New York State Spinal Cord fund, the NIH (NS 37060 to M.T.F., NS19259 to B.S.B.), the National Multiple Sclerosis Society, the Paralysed Veterans of America (P.H.), and core facility grants from the Research Centers for Minorities Institute-NIH and Specialized Neuroscience Research Programs-NIH (NS41073). J.Q. was a fellow of the NMSS.