Local injection of Lenti-Olig2 at lesion site promotes functional recovery of spinal cord injury in rats

CNS Neurosci Ther. 2017 Jun;23(6):475-487. doi: 10.1111/cns.12694. Epub 2017 Apr 27.

Abstract

Aims: Olig2 is one of the most critical factors during CNS development, which belongs to b-HLH transcription factor family. Previous reports have shown that Olig2 regulates the remyelination processes in CNS demyelination diseases models. However, the role of Olig2 in contusion spinal cord injury (SCI) and the possible therapeutic effects remain obscure. This study aims to investigate the effects of overexpression Olig2 by lentivirus on adult spinal cord injury rats.

Methods: Lenti-Olig2 expression and control Lenti-eGFP vectors were prepared, and virus in a total of 5 μL (108 TU/mL) was locally injected into the injured spinal cord 1.5 mm rostral and caudal near the epicenter. Immunostaining, Western blot, electron microscopy, and CatWalk analyzes were employed to investigate the effects of Olig2 on spinal cord tissue repair and functional recovery.

Results: Injection of Lenti-Olig2 significantly increased the number of oligodendrocytes lineage cells and enhanced myelination after SCI. More importantly, the introduction of Olig2 greatly improved hindlimb locomotor performances. Other oligodendrocyte-related transcription factors, which were downregulated or upregulated after injury, were reversed by Olig2 induction.

Conclusions: Our findings provided the evidence that overexpression Olig2 promotes myelination and locomotor recovery of contusion SCI, which gives us more understanding of Olig2 on spinal cord injury treatment.

Keywords: Olig2; lentivirus; myelin; oligodendrocytes; spinal cord injury.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Evoked Potentials, Motor / drug effects
  • Evoked Potentials, Motor / genetics
  • Evoked Potentials, Somatosensory / drug effects
  • Evoked Potentials, Somatosensory / genetics
  • Exploratory Behavior / drug effects
  • Female
  • Gangliosides / metabolism
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology
  • Hindlimb / drug effects
  • Hindlimb / physiopathology
  • Ki-67 Antigen / metabolism
  • Lentivirus / genetics
  • Locomotion / drug effects
  • Myelin Basic Protein / metabolism
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology
  • Myelin Sheath / ultrastructure
  • Nerve Tissue Proteins / metabolism
  • Oligodendrocyte Transcription Factor 2 / genetics
  • Oligodendrocyte Transcription Factor 2 / pharmacology
  • Oligodendrocyte Transcription Factor 2 / therapeutic use*
  • Oligodendrocyte Transcription Factor 2 / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / therapy*

Substances

  • Gangliosides
  • Ki-67 Antigen
  • Mbp protein, rat
  • Myelin Basic Protein
  • Nerve Tissue Proteins
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • ganglioside A2B5