Endoplasmic reticulum stress response in the rat contusive spinal cord injury model-susceptibility in specific cell types

Spinal Cord. 2014 Jan;52(1):9-16. doi: 10.1038/sc.2013.118. Epub 2013 Oct 22.

Abstract

Study design: Focus group study.

Objective: To investigate cell-specific endoplasmic reticulum (ER) stress reactions in contusive spinal cord by evaluating the expression of the glucose-regulated protein 78 (GRP78) and C/EBP homologous transcription factor protein (CHOP) using immunohistochemical staining.

Setting: Data were analysed at Tokai University School of Medicine in Japan.

Methods: The authors generated rat spinal cord injury (SCI) models using an IH-Impactor (100 kdyne(LI), 200 kdyne (HI)). Rats were killed at 1, 3, 5, 7 and 14 days post operation (dpo). Spinal cord sections were prepared and the expression ratio of GRP78 and CHOP was evaluated in oligodendrocyte precursor cells (OPCs) (NG2+), oligodendrocytes (OLs) (APC+), neurons (NeuN+) and astrocytes (GFAP+) using double immunohistochemical staining. We examined an area 8 mm distal from SCI-epicenter.

Results: Compared with the sham group, both injured groups had higher GRP78 expression ratio in contused spinal cord at 1 dpo. GRP78 expression ratio was highest in GFAP+ cells of both groups, and lowest in NG2+ cells. Although GRP78 was expressed strongly immediately after SCI in the both groups, increased CHOP expression was observed only in the HI group. The CHOP expression in NG2+ cells was significantly higher than that observed in GFAP+ cells at 5 dpo.

Conclusion: Although the ER stress response contributes to cell survival in the low-stress SCI conditions, the ER stress response induces an apoptotic cascade in high-stress SCI conditions. The ER response varies according to cell type, with the highest observed in astrocytes, and the lowest observed in oligodendrocyte precursor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress / physiology*
  • Heat-Shock Proteins / analysis*
  • Heat-Shock Proteins / biosynthesis
  • Immunohistochemistry
  • Male
  • Neurons / metabolism
  • Oligodendroglia / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology
  • Stem Cells / metabolism
  • Transcription Factor CHOP / analysis*
  • Transcription Factor CHOP / biosynthesis

Substances

  • Ddit3 protein, rat
  • GRP78 protein, rat
  • Heat-Shock Proteins
  • Transcription Factor CHOP