NeuroD1 overexpression in spinal neurons accelerates axonal regeneration after sciatic nerve injury

Muhua Lai; Mengjie Pan; Longjiao Ge; Jingmin Liu; Junyao Deng; Xianghai Wang; Lixia Li; Jinkun Wen; Dandan Tan; Haowen Zhang; Xiaofang Hu; Lanya Fu; Yizhou Xu; Zhenlin Li; Xiaozhong Qiu; Gong Chen; Jiasong Guo

doi:10.1016/j.expneurol.2020.113215

NeuroD1 overexpression in spinal neurons accelerates axonal regeneration after sciatic nerve injury

Exp Neurol. 2020 May:327:113215. doi: 10.1016/j.expneurol.2020.113215. Epub 2020 Jan 25.

Authors

Muhua Lai¹, Mengjie Pan², Longjiao Ge³, Jingmin Liu¹, Junyao Deng¹, Xianghai Wang¹, Lixia Li¹, Jinkun Wen¹, Dandan Tan¹, Haowen Zhang¹, Xiaofang Hu¹, Lanya Fu¹, Yizhou Xu¹, Zhenlin Li¹, Xiaozhong Qiu⁴, Gong Chen⁵, Jiasong Guo⁶

Affiliations

¹ 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.
² 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.
³ Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming, Yunnan, China.
⁴ Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, China.
⁵ Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China; Department of Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States.
⁶ 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; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangzhou, China. Electronic address: jiasongguo@smu.edu.cn.

PMID: 31991126
DOI: 10.1016/j.expneurol.2020.113215

Abstract

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.

Keywords: Axonal regeneration; BDNF; NeuroD1; Neuron; Sciatic nerve injury; Spastin; Spinal cord; TrkB.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Axons / metabolism*
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Brain-Derived Neurotrophic Factor / metabolism
Female
Mice
Motor Activity / physiology
Nerve Regeneration / physiology*
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Neurons / metabolism*
Peripheral Nerve Injuries / metabolism*
Peripheral Nerve Injuries / physiopathology
Receptor, trkB / metabolism
Recovery of Function / physiology
Sciatic Nerve / injuries*
Spinal Nerves / metabolism*

Substances

Basic Helix-Loop-Helix Transcription Factors
Brain-Derived Neurotrophic Factor
Nerve Tissue Proteins
Neurogenic differentiation factor 1
Receptor, trkB