Neurotoxicity of different amyloid beta subspecies in mice and their interaction with isoflurane anaesthesia

Laura Borgstedt, Manfred Blobner, Maximilian Musiol, Sebastian Bratke, Finn Syryca, Gerhard Rammes, Bettina Jungwirth, Sebastian Schmid

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Background The aim of this study was to assess different amyloid beta subspecies’ effects on behaviour and cognition in mice and their interaction with isoflurane anaesthesia. Methods After governmental approval, cannulas were implanted in the lateral cerebral ventricle. After 14 days the mice were randomly intracerebroventricularly injected with Aß 1–40 (Aß40), Aß 1–42 (Aß42), 3NTyr10-Aß (Aß nitro), AßpE3-42 (Aß pyro), or phosphate buffered saline. Four days after the injection, 30 mice (6 animals per subgroup) underwent general anaesthesia with isoflurane. A “sham” 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. Results Aß 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 Aß42 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. Conclusions Testing cognitive performance after intracerebroventricular injection of different amyloid beta subspecies revealed that Aß pyro might be less harmful, which was reversed by isoflurane anaesthesia. There is minor evidence for Aß42-mediated neurotoxicity. Preliminary molecular analysis of biomarkers did not clarify pathophysiological mechanisms.

Original languageEnglish
Article numbere0242989
JournalPLoS ONE
Issue number12 December
StatePublished - Dec 2020
Externally publishedYes


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