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Endoplasmic reticulum stress pathway mediates isoflurane-induced neuroapoptosis and cognitive impairments in aged rats.
- Source :
-
Physiology & behavior [Physiol Behav] 2015 Nov 01; Vol. 151, pp. 16-23. Date of Electronic Publication: 2015 Jul 08. - Publication Year :
- 2015
-
Abstract
- Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important clinical syndrome. Although it has been documented that volatile anesthetics induce neuronal apoptosis and cognitive deficits in several aged animal models, the underlying mechanisms are not well understood. Endoplasmic reticulum stress (ERS) is considered as an initial or early response of cells under stress and linked to neuronal death in various neurodegenerative diseases. The study was designed to explore the possible role of ERS pathway in isoflurane-induced neuroapoptosis and cognitive impairments. In the present study, twenty-month-old rats were exposed to 1.3% isoflurane for 4h. Two weeks later, the rats were subjected to behavioral study. Protein and mRNA expressions of ERS markers were evaluated. Meanwhile, hippocampal neuronal apoptosis was also detected. We found that isoflurane triggered ERS as evidenced by increased phosphorylation of eukaryotic initiation factor (EIF) 2α, and increased expression of 78-kDa glucose-regulated protein (GRP78), activating transcription factor (ATF) 4 and C/EBP homologous protein (CHOP). Furthermore, the level of apoptosis in the hippocampus was significantly up-regulated after isoflurane exposure, and salubrinal (ERS inhibitor) treatment attenuated the increase. More importantly, cognitive impairments caused by isoflurane were also effectively alleviated by salubrinal pretreatment. These results indicate that ERS-mediated apoptotic pathway is involved in isoflurane neurotoxicity in aged rats. Inhibition of ERS overactivation contributes to the relief of isoflurane-induced neurohistopathologic changes.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Activating Transcription Factors metabolism
Aging drug effects
Aging physiology
Aging psychology
Animals
Apoptosis physiology
Cognition Disorders physiopathology
Disease Models, Animal
Endoplasmic Reticulum Stress physiology
Heat-Shock Proteins metabolism
Hippocampus physiopathology
Male
Phosphorylation
Random Allocation
Rats, Sprague-Dawley
Transcription Factor CHOP metabolism
ran GTP-Binding Protein metabolism
Anesthetics, Inhalation toxicity
Apoptosis drug effects
Cognition Disorders chemically induced
Endoplasmic Reticulum Stress drug effects
Hippocampus drug effects
Isoflurane toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1873-507X
- Volume :
- 151
- Database :
- MEDLINE
- Journal :
- Physiology & behavior
- Publication Type :
- Academic Journal
- Accession number :
- 26162760
- Full Text :
- https://doi.org/10.1016/j.physbeh.2015.07.008