Cyclic AMP promotes axon regeneration, lesion repair and neuronal survival in lampreys after spinal cord injury

Lau, B. Y. B., Fogerson, S. M., Walsh, R. B., Morgan, J. R. (December 2013) Cyclic AMP promotes axon regeneration, lesion repair and neuronal survival in lampreys after spinal cord injury. Experimental Neurology, 250. pp. 31-42. ISSN 00144886 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/24041988
DOI: 10.1016/j.expneurol.2013.09.004

Abstract

Axon regeneration after spinal cord injury in mammals is inadequate to restore function, illustrating the need to design better strategies for improving outcomes. Increasing the levels of the second messenger cyclic adenosine monophosphate (cAMP) after spinal cord injury enhances axon regeneration across a wide variety of species, making it an excellent candidate molecule that has therapeutic potential. However, several important aspects of the cellular and molecular mechanisms by which cAMP enhances axon regeneration are still unclear, such as how cAMP affects axon growth patterns, the molecular components within growing axon tips, the lesion scar, and neuronal survival. To address these points, we took advantage of the large, identified reticulospinal (RS) neurons in lamprey, a vertebrate that exhibits robust axon regeneration after a complete spinal cord transection. Application of a cAMP analog, db-cAMP, at the time of spinal cord transection increased the number of axons that regenerated across the lesion site. Db-cAMP also promoted axons to regenerate in straighter paths, prevented abnormal axonal growth patterns, increased the levels of synaptotagmin within axon tips, and increased the number of axotomized neurons that survived after spinal cord injury, thereby increasing the pool of neurons available for regeneration. There was also a transient increase in the number of microglia/macrophages and improved repair of the lesion site. Taken together, these data reveal several new features of the cellular and molecular mechanisms underlying cAMP-mediated enhancement of axon regeneration, further emphasizing the positive roles for this conserved pathway. © 2013 Elsevier Inc.

Item Type: Paper
Uncontrolled Keywords: Axon regeneration Dibutyryl cyclic AMP (db-cAMP) Microglia/macrophages Neuroprotection Plasticity SV2 Synaptotagmin
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor > Cyclic AMP
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:
Communities: CSHL labs > Shea lab
Depositing User: Matt Covey
Date: December 2013
Date Deposited: 05 Nov 2013 22:08
Last Modified: 05 Nov 2013 22:08
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28828

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