Axons provide long-range communication in the nervous system. Regeneration of axons in the injured spinal cord brings the potential to reconnect the caudal spinal cord to rostral brain stem and cerebrum and restore sensory and motor function. Significant advances have been made in the field of neural repair that hold promise for restoring function in spinal cord injury, particularly when interventions can be combined to target multiple repair mechanisms. The studies proposed in this project will explore the intracellular mechanisms underlying improved functional recovery in spinal cord injury interventions, focusing on novel interactions in the axonal compartment. We will test the hypothesis that the microenvironment of the injured spinal cord and interventions aimed at overcoming the inhibitory microenvironment can modulate intraaxonal signaling events that converge on the local protein synthesis machinery and this contributes to axonal growth and maturation. We will test this hypothesis with two specific aims that bring together expertise of the principal investigator in axonal growth and intra-axonal signaling with expertise from Project III (Houle) in regenerative therapies for spinal cord injury and Project II (Fischer) in progenitor cell therapies for spinal cord injury.
The first aim of this project asks if exercise/training regiens that have been shown to improve recovery from spinal cord injury regulate axonal growth potential through post-transcriptional mechanisms. Both overall and intra-axonal translational control mechanisms will be tested using primary neuronal cultures and peripheral nerve grafting into the transected spinal cord.
The second aim will ask if precursor cells used for spinal cord injury can directly modulate intra-axonal signaling to regulate the intrinsic growth potential and maturation of axons through axonal mRNA transport and translational control mechanisms. We will integrate these data with Project II to address mRNA translation in host axons as they interact with grafted precursor cells in SCI. The overall objective of these experiments is to uncover mechanisms underlying enhanced axonal growth and signaling that can be used to rationally fine tune future neural repair strategies.
Axons have the ability to generate their own proteins needed for regeneration, but it is not clear if this occurs in the spinal cord or if neural repair strategies developed for spinal cord injury target this intra-axonal signaling mechanism. We will determine how growth supportive environments for spinal cord regeneration and training regimens that can improve functional recovery impact on axonal signal transduction and axon regrowth.
|Twiss, Jeffery L; Fainzilber, Mike (2016) Neuroproteomics: How Many Angels can be Identified in an Extract from the Head of a Pin? Mol Cell Proteomics 15:341-3|
|Detloff, Megan Ryan; Quiros-Molina, Daniel; Javia, Amy S et al. (2016) Delayed Exercise Is Ineffective at Reversing Aberrant Nociceptive Afferent Plasticity or Neuropathic Pain After Spinal Cord Injury in Rats. Neurorehabil Neural Repair 30:685-700|
|Sachdeva, Rahul; Farrell, Kaitlin; McMullen, Mary-Katharine et al. (2016) Dynamic Changes in Local Protein Synthetic Machinery in Regenerating Central Nervous System Axons after Spinal Cord Injury. Neural Plast 2016:4087254|
|Jin, Y; Bouyer, J; Shumsky, J S et al. (2016) Transplantation of neural progenitor cells in chronic spinal cord injury. Neuroscience 320:69-82|
|Sachdeva, Rahul; Theisen, Catherine C; Ninan, Vinu et al. (2016) Exercise dependent increase in axon regeneration into peripheral nerve grafts by propriospinal but not sensory neurons after spinal cord injury is associated with modulation of regeneration-associated genes. Exp Neurol 276:72-82|
|Yuan, Xiao-bing; Jin, Ying; Haas, Christopher et al. (2016) Guiding migration of transplanted glial progenitor cells in the injured spinal cord. Sci Rep 6:22576|
|Twiss, Jeffery L; Kalinski, Ashley L; Sachdeva, Rahul et al. (2016) Intra-axonal protein synthesis - a new target for neural repair? Neural Regen Res 11:1365-1367|
|Hayakawa, Kazuo; Haas, Christopher; Fischer, Itzhak (2016) Examining the properties and therapeutic potential of glial restricted precursors in spinal cord injury. Neural Regen Res 11:529-33|
|Jin, Ying; Bouyer, Julien; Haas, Christopher et al. (2015) Evaluation of the anatomical and functional consequences of repetitive mild cervical contusion using a model of spinal concussion. Exp Neurol 271:175-88|
|Hayakawa, Kazuo; Haas, Christopher; Jin, Ying et al. (2015) Glial restricted precursors maintain their permissive properties after long-term expansion but not following exposure to pro-inflammatory factors. Brain Res 1629:113-25|
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