Protective effect of a novel sigma‐1 receptor agonist is associated with reduced endoplasmic reticulum stress in stroke male mice

Ryuta Morihara; Toru Yamashita; Xia Liu; Yumiko Nakano; Yusuke Fukui; Kota Sato; Yasuyuki Ohta; Nozomi Hishikawa; Jingwei Shang

doi:10.1002/jnr.24270

journal article Aug 13, 2018

Protective effect of a novel sigma‐1 receptor agonist is associated with reduced endoplasmic reticulum stress in stroke male mice

Ryuta Morihara

Toru Yamashita Xia Liu

Yumiko Nakano Yusuke Fukui Kota Sato

Yasuyuki Ohta Nozomi Hishikawa Jingwei Shang

Journal of Neuroscience Research Vol. 96 No. 10 pp. 1707-1716 · Wiley

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Abstract

AbstractSigma‐1 receptor (Sig‐1R) is expressed at endoplasmic reticulum (ER) membranes, where it regulates a variety of specific physiological functions. However, the profile and exact roles of ER stress‐related molecules after Sig‐1R agonist treatment in an in vivo stroke model are largely unknown. The aim of this study is to investigate the effect of a novel Sig‐1R agonist, aniline derivative compound (Comp‐AD), on the ER stress response following ischemic stroke. Male C57BL/6J mice received transient middle cerebral artery occlusion for 90 min, and were then treated with vehicle saline or Comp‐AD at reperfusion. At 3 hr, 1 day, and 7 days after reperfusion, immunohis‐ tochemistry was performed for Sig‐1R and ER stress‐related proteins including phospho protein kinase RNA‐like endoplasmic reticulum kinase (p‐PERK), phospho inositol requiring enzyme 1α (p‐ IRE1α), and activating transcription factor 6 (ATF6). Neurobehavioral analysis showed improved functional recovery at 1 day and 7 days after reperfusion, and the infarct volume was significantly smaller at 7 days (p < .05), in the Comp‐AD group compared with the vehicle group. Comp‐AD treatment upregulated Sig‐1R immunoreactivity at 3 hr and 1 day (p < .05), and reduced p‐PERK and p‐IRE1α expression at 1 day (p < .05, respectively), in the peri‐ischemic region compared with the vehicle group. Treatment with the novel Sig‐1R agonist Comp‐AD was neuroprotective after transient middle cerebral artery occlusion, and was associated with upregulation of Sig‐1R and a reduction of ER stress.

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Details

Published: Aug 13, 2018
Vol/Issue: 96(10)
Pages: 1707-1716
License: View

Authors

R

Ryuta Morihara