Inhaled Anesthetic Enhancement of Amyloid-β Oligomerization and Cytotoxicity
Abstract
BACKGROUND: The majority of surgical patients receive inhaled anesthetics, principally small haloalkanes and haloethers. Long-term cognitive problems occur in the elderly subsequent to anesthesia and surgery, and previous surgery might also be a risk factor for neurodegenerative disorders like Alzheimer and Parkinson disease. The authors hypothesize that inhaled anesthetics contribute to these effects through a durable enhancement of peptide oligomerization. METHODS: Light scattering, filtration assays, electron microscopy, fluorescence spectroscopy and size-exclusion chromatography was used to characterize the concentration-dependent effects of halothane, isoflurane, propofol, and ethanol on amyloid beta peptide oligomerization. Pheochromocytoma cells were used to characterize cytotoxicity of amyloid oligomers with and without the above anesthetics. RESULTS: Halothane and isoflurane enhanced amyloid beta oligomerization rates and pheochromocytoma cytotoxicity in vitro through a preference for binding small oligomeric species. Ethanol and propofol inhibited oligomerization at low concentration but enhanced modestly at very high concentration. Neither ethanol nor propofol enhanced amyloid beta toxicity in pheochromocytoma cells. CONCLUSIONS: Inhaled anesthetics enhance oligomerization and cytotoxicity of Alzheimer disease-associated peptides. In addition to the possibility of a general mechanism for anesthetic neurotoxicity, these results call for further evaluation of the interaction between neurodegenerative disorders, dementia, and inhalational anesthesia.
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Acutely elevated Aβ oligomer levels have been noted after exposure to general anesthetics.
“Somewhat surprisingly, acutely elevated oligomer levels have been noted after exposure to general anesthetics (Eckenhoff et al., 2004).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Eckenhoff et al., 2004
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Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study
Møller, J. T., Cluitmans, P. P., Rasmussen, L., Houx, P. J., Rasmussen, H., Canet, J., Rabbitt, P., Jolles, J., Larsen, K., Hanning, C. D., et al. (1998) · The Lancet · doi:10.1016/s0140-6736(97)07382-0 · Cited by 2,407 · see citing works
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Hablitz, L. M., Vinitsky, H. S., Sun, Q., Stæger, F. F., Sigurdsson, B., Mortensen, K. N., Lilius, T. O., & Nedergaard, M. (2019) · Science Advances · doi:10.1126/sciadv.aav5447 · Cited by 629 · see citing works
The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease
Ferreira, S. T., & Klein, W. L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.08.003 · Cited by 442 · see citing works
Craddock, T. J. A., Kurian, P., Preto, J., Sahu, K., Hameroff, S. R., Klobukowski, M., & Tuszynski, J. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-09992-7 · Cited by 109 · see citing works
- Authors
- Eckenhoff, R. G., Johansson, J. S., Wei, H., Carnini, A., Kang, B., Wei, W., Pidikiti, R., Keller, J. M., & Eckenhoff, M. F.
- Affiliations
- University of Pennsylvania (US)
- Assistant Professor.
- Research Fellow.
- Research Specialist.
- Research Technician.
- Research Associate.
- Research Scientist, Department of Anesthesia.
- Venue
- Anesthesiology
- Published
- 2004-09-01
- Volume
- 101
- Issue
- 3
- Pages
- 703-709
- ISSN
- 0003-3022 (ISSN-L)
- OpenAlex
- W2016928060
- Cited by
- 376
- References
- 1
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 16 · 2023: 15 · 2022: 10 · 2021: 16 · 2020: 17 · 2019: 14 · 2018: 18 · 2017: 20 · 2016: 23 · 2015: 16 · 2014: 23 · 2013: 25 · 2012: 26
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 55876, P01GM055876)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Keywords
- inhalational anesthetics, amyloid-beta oligomerization, halothane, isoflurane, propofol, ethanol, anesthetic neurotoxicity, Alzheimer's disease, postoperative cognitive dysfunction, pheochromocytoma cells, neurodegenerative diseases
- MeSH terms
- Adrenal Gland Neoplasms, Ethanol, Animals, Central Nervous System Depressants, Chromatography, Gel, Fluorescent Dyes, Halothane, Image Processing, Computer-Assisted, Isoflurane, Kinetics, L-Lactate Dehydrogenase, Microscopy, Electron, Oligopeptides, Pheochromocytoma, Tumor Cells, Cultured, Propofol, Amyloid beta-Peptides, Anesthetics, Inhalation, Rats
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