Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK.
Applied Medical Science College, Shaqra University, P.O. Box 1678, Ad-Dawadmi 11911, Saudi Arabia.
Cells. 2021 Aug 6;10(8):2015. doi: 10.3390/cells10082015.
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.
中枢神经系统神经元由于多种内在和外在因素，一般无法在损伤后再生其轴突，包括轴突生长抑制分子的存在。其中一种有效的中枢神经系统轴突再生抑制剂是 RTN4 或 Nogo-A。在这里，我们专注于 RTN3，因为其对中枢神经系统轴突再生的贡献目前尚不清楚。我们发现，RTN3 的表达与损伤背柱后背根神经节神经元（DRGN）的轴突再生表型相关，背柱损伤是一种典型的脊髓损伤模型。RTN3 的过表达促进了体外 DRGN 突起的去抑制性生长，以及体内损伤后背柱轴突的再生/发芽以及电生理、感觉和运动功能的恢复。然而，突蛋白的敲低消除了 RTN3 增强的体外和体内突起/轴突再生。此外，在第二个中枢神经系统损伤模型——视神经挤压损伤模型中，RTN3 的过表达增强了视网膜神经节细胞（RGC）的存活，促进了体外神经突生长和体内存活和轴突再生，这种作用也依赖于突蛋白。这些结果表明，RTN3 以依赖突蛋白的方式增强了脊髓和视神经损伤后的神经突生长/轴突再生。
