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Overexpression of Reticulon 3 Enhances CNS Axon Regeneration and Functional Recovery after Traumatic Injury.
- Source :
-
Cells [Cells] 2021 Aug 06; Vol. 10 (8). Date of Electronic Publication: 2021 Aug 06. - Publication Year :
- 2021
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 10
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 34440784
- Full Text :
- https://doi.org/10.3390/cells10082015