Tau Phosphorylation and Sevoflurane Anesthesia: An Association to Postoperative Cognitive Impairment
Open accessAbstract
BACKGROUND: There is a growing interest in the involvement of anesthetic agents in the etiology of postoperative cognitive dysfunction. Recent animal studies suggest that acute anesthesia induces transient hyperphosphorylation of tau, an effect essentially ascribed to hypothermia. The main aim of the present study was to investigate effects, in normothermic conditions, of acute or repeated exposure to sevoflurane, a halogenated anesthetic agent, on hippocampal tau phosphorylation and spatial memory in adult mice. METHODS: 5 to 6-month-old C57Bl6/J mice were submitted to acute (1 h) or repeated (five exposures of 1h every month) anesthesia using 1.5 or 2.5% sevoflurane, in normothermic conditions. In the acute protocol, animals were sacrificed 1 and 24 h after exposure. In the chronic protocol, spatial memory was evaluated using the Morris water maze following the fourth exposure, and tau phosphorylation evaluated 1 month following the last exposure using bi- and mono-dimensional electrophoresis. RESULTS: Acute sevoflurane anesthesia in normothermic conditions led to a significant dose-dependent and reversible hippocampal tau phosphorylation, 1 h following the end of exposure (P < 0.001). Conversely, repeated anesthesia led to persistent tau hyperphosphorylation and significant memory impairments, as seen in the retention phase of the Morris water maze in sevoflurane-anesthesized animals. These pathologic features may be related to the activation of both Akt and Erk pathways. CONCLUSIONS: The present study demonstrates, in mice, that sevoflurane exposure is associated with increased tau phosphorylation through specific kinases activation and spatial memory deficits. These data support a correlation between exposures to this anesthetic agent and cognitive decline.
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Sevoflurane anaesthesia-induced postoperative cognitive deficits are associated with hyperphosphorylation of tau.
“sevoflurane anaesthesia-induced postoperative cognitive deficits are associated with the hyperphosphorylation of tau [152].”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [152]
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“In addition, sevoflurane anaesthesia-induced postoperative cognitive deficits are associated with the hyperphosphorylation of tau [152].”
Background
- Authors
- Le Freche, H., Brouillette, J., Fernandez-Gomez, F.-J., Patin, P., Caillierez, R., Zommer, N., Sergeant, N., Buée-Scherrer, V., Lebuffe, G., Blum, D., & Buée, L.
- Affiliations
- Chief Resident, Institut National de la Santé et de la Recherche Médicale, UMR837, Alzheimer & Tauopathies, Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France, and University of Lille, Faculté de Médecine, Jean-Pierre Aubert Research Centre, Lille, France, and Pôle d'Anesthésie-Réanimation, Hôpital Huriez, CHRU, Lille, France.
- Post-doctoral Fellow.
- Graduate Student.
- Engineer.
- Inserm (FR)
- Associate Professor.
- Université de Lille (FR)
- Centre National de la Recherche Scientifique (FR)
- Venue
- Anesthesiology
- Published
- 2012-04-01
- Volume
- 116
- Issue
- 4
- Pages
- 779-787
- ISSN
- 0003-3022 (ISSN-L)
- OpenAlex
- W2004541006
- Cited by
- 212
- References
- 59
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 11 · 2022: 17 · 2021: 15 · 2020: 10 · 2019: 18 · 2018: 20 · 2017: 12 · 2016: 16 · 2015: 21 · 2014: 26 · 2013: 16 · 2012: 8
- FWCI
- 7.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-08-MNPS-0002, ANR-07-JCJC-0107)
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- sevoflurane, tau phosphorylation, postoperative cognitive dysfunction, hippocampus, spatial memory, anesthetic neurotoxicity, normothermia, AKT pathway, ERK signaling, repeated anesthesia, cognitive decline
- MeSH terms
- Sevoflurane, Acute Disease, Anesthesia, General, Animals, Chronic Disease, Cognition Disorders, Female, Methyl Ethers, Mice, Inbred C57BL, Phosphorylation, Postoperative Complications, tau Proteins, Mice
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