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Cyclic AMP elevates tubulin expression without increasing intrinsic axon growth capacity
Paul J Han1, Salil Shukla, Prem S Subramanian
1Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21205-2196, USA.
Experimental Neurology
|September 24, 2004
Summary
Elevated cAMP levels in neurons, induced by conditioning lesions or db-cAMP, promote axon regeneration. However, db-cAMP only partially mimics the effects of conditioning lesions on axon growth capacity.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Central nervous system (CNS) myelin inhibits axon regeneration.
- Conditioning lesions (CL) enhance intrinsic axon growth capacity and promote regeneration.
- Cyclic adenosine monophosphate (cAMP) is implicated in mediating CL-induced regeneration.
Purpose of the Study:
- To investigate whether elevated cAMP levels are responsible for all observed effects of a CL.
- To compare the effects of db-cAMP and CL on axon regeneration and growth-associated protein expression.
Main Methods:
- Intraganglionic injection of dibutyryl cAMP (db-cAMP) in rat dorsal root ganglion (DRG) neurons.
- Assessment of growth-associated tubulin isotype expression.
- Measurement of tubulin transport velocity in slow component b (SCb).
- Evaluation of peripheral and central axon regeneration in vivo.
Main Results:
- db-cAMP increased growth-associated tubulin isotype expression, similar to CL.
- db-cAMP did not increase tubulin delivery velocity via SCb.
- db-cAMP failed to significantly enhance peripheral nerve regeneration or long-distance central axon elongation in permissive grafts.
Conclusions:
- Elevated cAMP levels contribute to some, but not all, of the regenerative changes induced by CL.
- cAMP signaling is crucial for increasing growth-associated protein expression but not for enhancing tubulin transport or intrinsic growth capacity sufficiently for robust regeneration.