title: Dynamic Changes in Local Protein Synthetic Machinery in Regenerating Central Nervous System Axons after Spinal Cord Injury.
abstract: Intra-axonal localization of mRNAs and protein synthesis machinery (PSM) endows neurons with the capacity to generate proteins locally, allowing precise spatiotemporal regulation of the axonal response to extracellular stimuli. A number of studies suggest that this local translation is a promising target to enhance the regenerative capacity of damaged axons. Using a model of central nervous system (CNS) axons regenerating into intraspinal peripheral nerve grafts (PNGs) we established that adult regenerating CNS axons contain several different mRNAs and protein synthetic machinery (PSM) components in vivo. After lower thoracic level spinal cord transection, ascending sensory axons regenerate into intraspinal PNGs but axon growth is stalled when they reach the distal end of the PNG (3 versus 7 weeks after grafting, resp.). By immunofluorescence with optical sectioning of axons by confocal microscopy, the total and phosphorylated forms of PSMs are significantly lower in stalled compared with actively regenerating axons. Reinjury of these stalled axons increased axonal localization of the PSM proteins, indicative of possible priming for a subcellular response to axotomy. These results suggest that axons downregulate protein synthetic capacity as they cease growing, yet they retain the ability to upregulate PSM after a second injury.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Sachdeva
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Farrell
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Mary-Katharine
authors.initials: MK
authors.lastname: McMullen
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Twiss
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Houle
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D005260:Female; D009416:Nerve Regeneration / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000601:surgery; D013904:Thoracic Vertebrae; D013979:Tibial Nerve / Q000378:metabolism* / Q000637:transplantation*; D016378:Tissue Transplantation / Q000379:methods