Evidence map›Paper›PMID 33270674›Full record

ArticlePloS one2020

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

Abstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Laura BorgstedtDepartment of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.ORCID 0000-0002-9729-0723
Manfred BlobnerDepartment of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.ORCID 0000-0002-0370-5247
Maximilian MusiolDepartment of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.ORCID 0000-0003-3241-8148
Sebastian BratkeDepartment of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Finn SyrycaDepartment of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Gerhard RammesDepartment of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Bettina JungwirthDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Ulm, Ulm University, Ulm, Germany.ORCID 0000-0001-9749-7460
Sebastian SchmidDepartment of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.ORCID 0000-0002-1232-5350

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe aim of this study was to assess different amyloid beta subspecies' effects on behaviour and cognition in mice and their interaction with isoflurane anaesthesia.

methodsAfter governmental approval, cannulas were implanted in the lateral cerebral ventricle. After 14 days the mice were randomly intracerebroventricularly injected with Aβ 1-40 (Aβ40), Aβ 1-42 (Aβ42), 3NTyr10-Aβ (Aβ nitro), AβpE3-42 (Aβ 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.

resultsAβ 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 Aβ42 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.

conclusionsTesting cognitive performance after intracerebroventricular injection of different amyloid beta subspecies revealed that Aβ pyro might be less harmful, which was reversed by isoflurane anaesthesia. There is minor evidence for Aβ42-mediated neurotoxicity. Preliminary molecular analysis of biomarkers did not clarify pathophysiological mechanisms.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnesthetics, InhalationAnimalsBehavior, AnimalBrainCaspase 3CognitionExploratory BehaviorInjections, IntraventricularIsofluraneMaleMice, Inbred C57BLNeurotoxicity SyndromesPeptide FragmentsReceptor, Metabotropic Glutamate 5Amyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Anesthetics, InhalationCasp3 protein, mouseCaspase 3IsofluraneNR2B protein (1292-1308)Peptide FragmentsReceptor, Metabotropic Glutamate 5Receptors, N-Methyl-D-AspartateTumor Necrosis Factor-alpha

Identifiers

PMID33270674
PMCPMC7714346

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.