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Title
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The intracerebral injection of Aβ1-42 oligomers does not invariably alter seizure susceptibility in mice
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Author
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Abstract
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| Objectives: Epileptiform activity and seizures are present in patients with Alzheimer's disease (AD) and genetic animal models of AD. Amyloid beta 1-42 (A beta(1-42)) oligomers are thought to be crucial in AD and can cause neuronal hyperexcitability in vitro. However, it is unclear whether these A beta(1-42) oligomers cause the increased seizure susceptibility in vivo in people with AD and in AD animal models, nor via which mechanisms it would do so. We investigated this question by injecting A beta(1-42) oligomers intracerebrally in mice and assessed its impact on seizure susceptibility. Materials and methods: We performed a single intracerebral injection of synthetic A beta(1-42) oligomers or scrambled A beta(1-42) in NMRI mice in three different cohorts and subjected them to an i.v. infusion of a chemoconvulsant. We evoked the seizures 1.5 h, 1week, or 3weeks after the intracerebral injection of A beta(1-42) oligomers, covering also the timepoints and injection locations that were used by others in similar experimental set-ups. Results: With a thioflavine T assay and transmission electron microscopy we confirmed that A beta(1-42) monomers spontaneously aggregated to oligomers. We did not find an effect of A beta(1-42) oligomers on susceptibility to seizures - evoked 1.5 h, 1week or 3weeks - after their intracerebral injection. Significance: The lack of effect of A beta(1-42) oligomers on seizure susceptibility in our experiments contrasts with recent findings in similar experimental set-ups. Contradicting conclusions are frequent in experiments with A beta(1-42) and they are often attributed to subtle differences in the various aggregation forms of the A beta(1-42) used in different experiments. We confirmed the presence of A beta(1-42) oligomers with state-of-the-art methods but cannot ascertain that the protein aggregates we used are identical to those used by others. Whether our findings or those previously published best represent the role of A beta(1-42) oligomers on seizures in AD remains unclear. |
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Language
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English
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Source (journal)
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Frontiers in aging neuroscience. - Lausanne, 2009, currens
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Publication
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Lausanne
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Frontiers Research Foundation
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2023
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ISSN
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1663-4365
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DOI
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10.3389/FNAGI.2023.1239140
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Volume/pages
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15
(2023)
, p. 1-10
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Article Reference
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1239140
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ISI
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001070075400001
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Pubmed ID
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37744393
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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