{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T08:42:17Z","timestamp":1769848937890,"version":"3.49.0"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009394","name":"Fakult\u00e4t f\u00fcr Medizin, Technische Universit\u00e4t M\u00fcnchen","doi-asserted-by":"publisher","award":["Institutional Support"],"award-info":[{"award-number":["Institutional Support"]}],"id":[{"id":"10.13039\/501100009394","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>The aim of this study was to assess different amyloid beta subspecies\u2019 effects on behaviour and cognition in mice and their interaction with isoflurane anaesthesia.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>After governmental approval, cannulas were implanted in the lateral cerebral ventricle. After 14 days the mice were randomly intracerebroventricularly injected with A\u03b2 1\u201340 (A\u03b240), A\u03b2 1\u201342 (A\u03b242), 3NTyr10-A\u03b2 (A\u03b2 nitro), A\u03b2pE3-42 (A\u03b2 pyro), or phosphate buffered saline. Four days after the injection, 30 mice (6 animals per subgroup) underwent general anaesthesia with isoflurane. A \u201csham\u201d anaesthetic procedure was performed in another 30 mice (6 animals per subgroup, 10 subgroups in total). During the next eight consecutive days a blinded assessor evaluated behavioural and cognitive performance using the modified hole-board test. Following the testing we investigated 2 brains per subgroup for insoluble amyloid deposits using methoxy staining. We used western blotting in 4 brains per subgroup for analysis of tumour-necrosis factor alpha, caspase 3, glutamate receptors NR2B, and mGlu5. Data were analysed using general linear modelling and analysis of variance.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>A\u03b2 pyro improved overall cognitive performance (p = 0.038). This cognitive improvement was reversed by isoflurane anaesthesia (p = 0.007), presumably mediated by decreased exploratory behaviour (p = 0.022 and p = 0.037). Injection of A\u03b242 was associated with increased anxiety (p = 0.079). Explorative analysis on a limited number of brains did not reveal insoluble amyloid deposits or differences in the expression of tumour-necrosis factor alpha, NR2B, mGlu5, or caspase 3.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>Testing cognitive performance after intracerebroventricular injection of different amyloid beta subspecies revealed that A\u03b2 pyro might be less harmful, which was reversed by isoflurane anaesthesia. There is minor evidence for A\u03b242-mediated neurotoxicity. Preliminary molecular analysis of biomarkers did not clarify pathophysiological mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0242989","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T19:24:43Z","timestamp":1607023483000},"page":"e0242989","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Neurotoxicity of different amyloid beta subspecies in mice and their interaction with isoflurane anaesthesia"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9729-0723","authenticated-orcid":true,"given":"Laura","family":"Borgstedt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0370-5247","authenticated-orcid":true,"given":"Manfred","family":"Blobner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3241-8148","authenticated-orcid":true,"given":"Maximilian","family":"Musiol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Bratke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Finn","family":"Syryca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Rammes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-7460","authenticated-orcid":true,"given":"Bettina","family":"Jungwirth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1232-5350","authenticated-orcid":true,"given":"Sebastian","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"issue":"4","key":"pone.0242989.ref001","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1056\/NEJMra0909142","article-title":"Alzheimer's disease.","volume":"362","author":"HW Querfurth","year":"2010","journal-title":"N Engl J Med"},{"issue":"3","key":"pone.0242989.ref002","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/alzrt258","article-title":"Truncated and modified amyloid-beta species.","volume":"6","author":"MP Kummer","year":"2014","journal-title":"Alzheimer's research & therapy."},{"issue":"10","key":"pone.0242989.ref003","doi-asserted-by":"crossref","first-page":"5147","DOI":"10.1021\/cr3000994","article-title":"The amyloid beta peptide: a chemist's perspective. 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