System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish 9 citations

PubMed: 36337694 DOI: 10.3389/fnagi.2022.990679

Sevoflurane exposure causes neuronal apoptosis and cognitive dysfunction by inducing ER stress activation of the inositol 1, 4, 5-trisphosphate receptor.

Front Aging Neurosci 14:990679

Authors: Qi Zhang, Yanan Li, Xupeng Wang, Chunping Yin, Qi Zhou, Junfei Guo, Juan Zhao, Xiaohui Xian, Zhiyong Hou, Qiujun Wang

Affiliations

  • Department of Anesthesiology, Children's Hospital of Hebei Province Affiliated to Hebei Medical University, Shijiazhuang, China.
  • Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
  • Department of Orthopaedics, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
  • Experimental Centre for Teaching, Hebei Medical University, Shijiazhuang, China.
  • Department of Pathophysiology, Hebei Medical University, Shijiazhuang, China.

Abstract

The role of the inositol 1, 4, 5-trisphosphate receptor (IP3R) in hippocampal neuronal apoptosis and cognitive dysfunction induced by sevoflurane is currently unclear. Therefore, in this study, we investigated the role of the IP3R in endoplasmic reticulum (ER) stress and hippocampal neuronal apoptosis induced by sevoflurane in aged rats and isolated hippocampal neurons using both and experiments, including bioinformatics, functional enrichment analysis, gene set enrichment analysis, hematoxylin, and eosin staining, TUNEL assay, flow cytometry, western blot analysis and transmission electron microscopy. Furthermore, behavioral assessment was performed with the Morris water maze test. We identified 232 differentially expressed genes induced by sevoflurane exposure, including 126 upregulated genes and 106 downregulated genes. Sevoflurane exposure caused cognitive impairment and neuronal injury, and increased p-IP3R levels and ER stress. An IP3R inhibitor, 2-APB, suppressed these changes, while an IP3R agonist, FK-506, aggravated these changes. Together, these findings suggest that sevoflurane exposure causes marked cognitive dysfunction in aged rats and neuronal injury in isolated hippocampal neurons by activating the IP3R and inducing cytoplasmic calcium overload, thereby resulting in ER stress and hippocampal neuronal apoptosis. GRAPHICAL ABSTRACT.

MeSH

Aged, Neurons, Apoptosis, Stress, Physiological, Calcium, Genes, Inositol, Cognitive Dysfunction, Sevoflurane, Morris Water Maze Test

Cited by