Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China; Department of Histology and Embryology, Southern Medical University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China; Department of Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States.
Exp Neurol. 2020 May;327:113215. doi: 10.1016/j.expneurol.2020.113215. Epub 2020 Jan 25.
Neurogenic differentiation 1 (NeuroD1) is mainlyexpressed in developing neurons where it plays critical roles in neuronal maturation and neurite elongation. The potential role and mechanism of NeuroD1 in adult axonal regeneration is not clear. The present study used synapsin (SYN) Cre and AAV9-Flex vectors to conditionally overexpress NeuroD1 in adult spinal neurons and found that NeuroD1 overexpression significantly accelerated axonal regeneration and functional recovery after sciatic nerve injury. Further in vitro and in vivo experiments suggested that the mechanism of NeuroD1 promotion on axonal regeneration was related to its regulation of the expression of neurotrophin BDNF and its receptor TrkB as well as a microtubule severing protein spastin.
神经发生素 1(NeuroD1)主要表达于发育中的神经元,在神经元成熟和轴突伸长中发挥关键作用。NeuroD1 在成年轴突再生中的潜在作用和机制尚不清楚。本研究采用突触素(SYN)Cre 和 AAV9-Flex 载体在成年脊髓神经元中条件性过表达 NeuroD1,发现 NeuroD1 过表达可显著加速坐骨神经损伤后的轴突再生和功能恢复。进一步的体外和体内实验表明,NeuroD1 促进轴突再生的机制与其对神经营养因子 BDNF 及其受体 TrkB 的表达的调节以及微管切割蛋白 spastin 有关。