CNS axons globally increase axonal transport after peripheral conditioning.
Despite the inability of CNS axons to regenerate, an increased regenerative capacity can be elicited following conditioning lesion to the peripheral branch of dorsal root ganglia neurons (DRGs). By in vivo radiolabeling of rat DRGs, coupled to mass spectrometry and kinesin immunoprecipitation of spinal cord extracts, we determined that the anterograde transport of cytoskeleton components, metabolic enzymes and axonal regeneration enhancers, was increased in the central branch of DRGs following a peripheral conditioning lesion. Axonal transport of mitochondria was also increased in the central branch of Thy1-MitoCFP mice following a peripheral injury. This effect was generalized and included augmented transport of lysosomes and synaptophysin- and APP-carrying vesicles. Changes in axonal transport were only elicited by a peripheral lesion and not by spinal cord injury. In mice, elevated levels of motors and of polyglutamylated and tyrosinated tubulin were present following a peripheral lesion and can explain the increase in axonal transport induced by conditioning. In summary, our work shows that a peripheral injury induces a global increase in axonal transport that is not restricted to the peripheral branch, and that, by extending to the central branch, allows a rapid and sustained support of regenerating central axons.
Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), University of Porto, 4150-180 Porto, Portugal, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), 4050-313 Porto, Portugal, and Institute of Neuronal Cell Biology, Munich Cluster for Systems Neurology and German Center for Neurodegenerative Diseases, Technische Universität München, 80802 München, Germany.
Fernando M
FM
Mar
Anabel R
AR
Simões
Sérgio
S
Leite
Marlene M
MM
Morgado
Telma E
TE
Santos
Inês S
IS
Rodrigo
Carla A
CA
Teixeira
Thomas
T
Misgeld
Mónica M
MM
Sousa
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D005727:Ganglia, Spinal / Q000502:physiology; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016708:Synaptophysin / Q000378:metabolism
D016708:Synaptophysin; D000242:Cyclic AMP
axon regeneration; axonal transport; conditioning lesion