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

29 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

Fingerprint

Endoplasmic Reticulum Stress
Spinal Cord
Ischemia
Motor Neurons
Interneurons
Activating Transcription Factor 4
Spinal Cord Ischemia
Reperfusion
Eukaryotic Initiation Factor-2
Paraplegia
Inositol
Thoracic Aorta
Endoplasmic Reticulum
Protein Isoforms
Cell Death
Catheters
Western Blotting
Rabbits
Neurons

Keywords

  • Endoplasmic reticulum stress
  • Ischemia/Reperfusion
  • Spinal cord

ASJC Scopus subject areas

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

Cite this

Impact of the endoplasmic reticulum stress response in spinal cord after transient ischemia. / Yamauchi, Takashi; Sakurai, Masahiro; Abe, Koji; Matsumiya, Goro; Sawa, Yoshiki.

In: Brain Research, Vol. 1169, No. 1, 12.09.2007, p. 24-33.

Research output: Contribution to journalArticle

Yamauchi, Takashi ; Sakurai, Masahiro ; Abe, Koji ; Matsumiya, Goro ; Sawa, Yoshiki. / Impact of the endoplasmic reticulum stress response in spinal cord after transient ischemia. In: Brain Research. 2007 ; Vol. 1169, No. 1. pp. 24-33.
@article{164ed3d78d7c4fca82d6cb9247b45e44,
title = "Impact of the endoplasmic reticulum stress response in spinal cord after transient ischemia",
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.",
keywords = "Endoplasmic reticulum stress, Ischemia/Reperfusion, Spinal cord",
author = "Takashi Yamauchi and Masahiro Sakurai and Koji Abe and Goro Matsumiya and Yoshiki Sawa",
year = "2007",
month = "9",
day = "12",
doi = "10.1016/j.brainres.2007.06.093",
language = "English",
volume = "1169",
pages = "24--33",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Impact of the endoplasmic reticulum stress response in spinal cord after transient ischemia

AU - Yamauchi, Takashi

AU - Sakurai, Masahiro

AU - Abe, Koji

AU - Matsumiya, Goro

AU - Sawa, Yoshiki

PY - 2007/9/12

Y1 - 2007/9/12

N2 - 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.

AB - 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.

KW - Endoplasmic reticulum stress

KW - Ischemia/Reperfusion

KW - Spinal cord

UR - http://www.scopus.com/inward/record.url?scp=34548513249&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548513249&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2007.06.093

DO - 10.1016/j.brainres.2007.06.093

M3 - Article

C2 - 17707355

AN - SCOPUS:34548513249

VL - 1169

SP - 24

EP - 33

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -