1. Overexpression of Reticulon 3 Enhances CNS Axon Regeneration and Functional Recovery after Traumatic Injury.
- Author
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Alhajlah S, Thompson AM, and Ahmed Z
- Subjects
- Animals, Axons pathology, Behavior, Animal, Carrier Proteins genetics, Cells, Cultured, Disease Models, Animal, Female, Ganglia, Spinal pathology, Motor Activity, Optic Nerve Injuries genetics, Optic Nerve Injuries pathology, Optic Nerve Injuries physiopathology, Rats, Sprague-Dawley, Retinal Ganglion Cells pathology, Signal Transduction, Spinal Cord Injuries genetics, Spinal Cord Injuries pathology, Spinal Cord Injuries physiopathology, Up-Regulation, Vesicular Transport Proteins genetics, Vesicular Transport Proteins metabolism, Rats, Axons metabolism, Carrier Proteins metabolism, Ganglia, Spinal metabolism, Nerve Regeneration, Neuronal Outgrowth, Optic Nerve Injuries metabolism, Retinal Ganglion Cells metabolism, Spinal Cord Injuries metabolism
- Abstract
CNS neurons are generally incapable of regenerating their axons after injury due to several intrinsic and extrinsic factors, including the presence of axon growth inhibitory molecules. One such potent inhibitor of CNS axon regeneration is Reticulon (RTN) 4 or Nogo-A. Here, we focused on RTN3 as its contribution to CNS axon regeneration is currently unknown. We found that RTN3 expression correlated with an axon regenerative phenotype in dorsal root ganglion neurons (DRGN) after injury to the dorsal columns, a well-characterised model of spinal cord injury. Overexpression of RTN3 promoted disinhibited DRGN neurite outgrowth in vitro and dorsal column axon regeneration/sprouting and electrophysiological, sensory and locomotor functional recovery after injury in vivo. Knockdown of protrudin, however, ablated RTN3-enhanced neurite outgrowth/axon regeneration in vitro and in vivo. Moreover, overexpression of RTN3 in a second model of CNS injury, the optic nerve crush injury model, enhanced retinal ganglion cell (RGC) survival, disinhibited neurite outgrowth in vitro and survival and axon regeneration in vivo, an effect that was also dependent on protrudin. These results demonstrate that RTN3 enhances neurite outgrowth/axon regeneration in a protrudin-dependent manner after both spinal cord and optic nerve injury.
- Published
- 2021
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