{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:07:11Z","timestamp":1777396031064,"version":"3.51.4"},"reference-count":87,"publisher":"SAGE Publications","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,11,23]]},"abstract":"<jats:p>Background: Studies suggest that general anesthetics like isoflurane and sevoflurane may aggravate Alzheimer\u2019s disease (AD) neuropathogenesis, e.g., increased amyloid-\u03b2 (A\u03b2) protein aggregation resulting in synaptotoxicity and cognitive dysfunction. Other studies showed neuroprotective effects, e.g., with xenon. Objective: In the present study, we want to detail the interactions of inhalational anesthetics with A\u03b2-derived pathology. We hypothesize xenon-mediated beneficial mechanisms regarding A\u03b2 oligomerization and A\u03b2-mediated neurotoxicity on processes related to cognition. Methods: Oligomerization of A\u03b21\u201342 in the presence of anesthetics has been analyzed by means of TR-FRET and silver staining. For monitoring changes in neuronal plasticity due to anesthetics and A\u03b21\u201342, A\u03b21\u201340, pyroglutamate-modified amyloid-(A\u03b2pE3), and nitrated A\u03b2 (3NTyrA\u03b2), we quantified long-term potentiation (LTP) and spine density. We analyzed network activity in the hippocampus via voltage-sensitive dye imaging (VSDI) and cognitive performance and A\u03b2 plaque burden in transgenic AD mice (ArcA\u03b2) after anesthesia. Results: Whereas isoflurane and sevoflurane did not affect A\u03b21\u201342 aggregation, xenon alleviated the propensity for aggregation and partially reversed A\u03b2pE3 induced synaptotoxic effects on LTP. Xenon and sevoflurane reversed A\u03b21\u201342-induced spine density attenuation. In the presence of A\u03b21\u201340 and A\u03b2pE3, anesthetic-induced depression of VSDI-monitored signaling recovered after xenon, but not isoflurane and sevoflurane removal. In slices pretreated with A\u03b21\u201342 or 3NTyrA\u03b2, activity did not recover after washout. Cognitive performance and plaque burden were unaffected after anesthetizing WT and ArcA\u03b2 mice. Conclusion: None of the anesthetics aggravated A\u03b2-derived AD pathology in vivo. However, A\u03b2 and anesthetics affected neuronal activity in vitro, whereby xenon showed beneficial effects on A\u03b21\u201342 aggregation, LTP, and spine density.<\/jats:p>","DOI":"10.3233\/jad-201185","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T18:33:23Z","timestamp":1634322803000},"page":"1193-1218","source":"Crossref","is-referenced-by-count":7,"title":["Inhalational Anesthetics Do Not Deteriorate Amyloid-\u03b2-Derived Pathophysiology in Alzheimer\u2019s Disease: Investigations on the Molecular, Neuronal, and Behavioral Level"],"prefix":"10.1177","volume":"84","author":[{"given":"Carolin","family":"Hofmann","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika","family":"Sander","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing Xing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Buerge","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Jungwirth","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany"},{"name":"Department of Anesthesiology, University Hospital Ulm, Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Borgstedt","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Kreuzer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Kopp","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Schorpp","sequence":"additional","affiliation":[{"name":"Assay Development and Screening Platform, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum M\u00fcnchen, Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamyar","family":"Hadian","sequence":"additional","affiliation":[{"name":"Assay Development and Screening Platform, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum M\u00fcnchen, Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten T.","family":"Wotjak","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Psychiatry, Neuronal Plasticity, Munich, Germany"},{"name":"Central Nervous System Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. 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