Cyclic AMP elevates tubulin expression without increasing intrinsic axon growth capacity.
Exposing rat dorsal root ganglion (DRG) neurons to dibutyryl cAMP (db-cAMP) enables central branches to regenerate in the spinal cord by nullifying the ability of CNS myelin to inhibit elongation. A conditioning lesion (CL) promotes similar regeneration of central branches in the spinal cord by increasing neuronal cAMP levels. It is a matter of speculation whether any of the other effects of a CL are triggered by elevated cAMP. We found that like a CL, intraganglionic injection of db-cAMP increases the expression of growth-associated tubulin isotypes. However, unlike a CL, db-cAMP does not increase the velocity at which tubulin is delivered to the tips of growing axons by slow component b (SCb). db-cAMP also fails to increase intrinsic axon growth capacity enough to raise the rate of regeneration of peripheral branches in the sciatic nerve or enable central branches to elongate long distances in an environment free of all CNS inhibitors of elongation (i.e., a peripheral nerve graft transplanted into the spinal cord at the site of dorsal column transection). Thus, the increase in cAMP induced by a CL induces some, but not all, of the changes that may be necessary to increase intrinsic axon growth capacity.
Han
Paul J
PJ
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21205-2196, USA.
Shukla
Salil
S
Subramanian
Prem S
PS
Hoffman
Paul N
PN
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020439:Growth Cones / Q000187:drug effects* / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010525:Peripheral Nerves / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016378:Tissue Transplantation / Q000502:physiology; D014404:Tubulin / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D006131:Growth Inhibitors; D014404:Tubulin; D003994:Bucladesine