Impact of the endoplasmic reticulum stress response in spinal cord after transient ischemia

Takashi Yamauchi, Masahiro Sakurai, Koji Abe, Goro Matsumiya, Yoshiki Sawa

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Delayed paraplegia after operation of the thoracic aorta is considered to be related to vulnerability of motor neurons to ischemia. Recently, endoplasmic reticulum (ER) stress has been reported to participate in neuronal cell death. In the present study, we investigate the expression of ER stress-related molecules and discuss the relationship between neuronal vulnerability and ER stress after transient ischemia in the spinal cord. Methods: A rabbit spinal cord ischemia model was generated using a balloon catheter. In this model, spinal motor neurons show selectively delayed neuronal death whereas other spinal neuron, such as interneurons, survive. Immunohistochemical analysis and Western blotting for ER stress-related molecules, including phosphorylated eukaryotic initiation factor 2 alpha (p-eIF2α), activating transcription factor 4 (ATF4), glucose-regulated protein 78 (GRP78) and inositol-requiring ER transmembrane RNAse α isoform (IRE1α), were examined. Results: P-eIF2α, which inhibits protein synthesis and modulates ER stress, was induced only in interneurons after 6 h of reperfusion. ATF4, which is specifically activated by PERK-eIF2α, was induced only in interneurons between 6 h and 1 day after reperfusion. GRP78 was induced strongly both in interneurons and motor neurons at an early stage of reperfusion, but prolonged expression was observed only in interneurons. IRE1α, which is supposed to transduce an ER stress-related death signal, was expressed more strongly and over a more prolonged period in motor neurons. Conclusions: These results indicate that the vulnerability of motor neurons in the spinal cord might be partially attributed to an ER stress response to transient ischemia.

Original languageEnglish
Pages (from-to)24-33
Number of pages10
JournalBrain Research
Volume1169
Issue number1
DOIs
Publication statusPublished - Sep 12 2007

Keywords

  • Endoplasmic reticulum stress
  • Ischemia/Reperfusion
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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