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Dynamic Changes in Local Protein Synthetic Machinery in Regenerating Central Nervous System Axons after Spinal Cord Injury
Journal article   Open access   Peer reviewed

Dynamic Changes in Local Protein Synthetic Machinery in Regenerating Central Nervous System Axons after Spinal Cord Injury

Rahul Sachdeva, Kaitlin Farrell, Mary-Katharine McMullen, Jeffery L Twiss and John D Houle
Neural plasticity, v 2016, 4087254
2016
PMID: 27375904
url
https://doi.org/10.1155/2016/4087254View
Published, Version of Record (VoR)CC BY V4.0 Open

Abstract

Animals Axons - metabolism Central Nervous System - metabolism Female Nerve Regeneration - physiology Protein Biosynthesis - physiology Rats Rats, Sprague-Dawley Spinal Cord Injuries - metabolism Spinal Cord Injuries - surgery Thoracic Vertebrae Tibial Nerve - metabolism Tibial Nerve - transplantation Tissue Transplantation - methods
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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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