The intracerebral injection of Aβ 1-42 oligomers does not invariably alter seizure susceptibility in mice.

Autor:	Vande Vyver M; Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.; Department of Neurology and Bru-BRAIN, Universitair Ziekenhuis Brussel, Brussels, Belgium.; NEUR Research Group, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.; Department of Biomedical Sciences, Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium., Daeninck L; Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium., De Smet G; Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium., Aourz N; Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium., Sahu S; Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium., Engelborghs S; Department of Neurology and Bru-BRAIN, Universitair Ziekenhuis Brussel, Brussels, Belgium.; NEUR Research Group, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.; Department of Biomedical Sciences, Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium., Pauwels K; RESEARCH Department, Vrije Universiteit Brussel, Brussels, Belgium., De Bundel D; Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium., Smolders I; Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.
Jazyk:	angličtina
Zdroj:	Frontiers in aging neuroscience [Front Aging Neurosci] 2023 Sep 07; Vol. 15, pp. 1239140. Date of Electronic Publication: 2023 Sep 07 (Print Publication: 2023).
DOI:	10.3389/fnagi.2023.1239140
Abstrakt:	Objectives: Epileptiform activity and seizures are present in patients with Alzheimer's disease (AD) and genetic animal models of AD. Amyloid beta 1-42 (Aβ 1-42 ) oligomers are thought to be crucial in AD and can cause neuronal hyperexcitability in vitro . However, it is unclear whether these Aβ 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 Aβ 1-42 oligomers intracerebrally in mice and assessed its impact on seizure susceptibility. Materials and Methods: We performed a single intracerebral injection of synthetic Aβ 1-42 oligomers or scrambled Aβ 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, 1 week, or 3 weeks after the intracerebral injection of Aβ 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 Aβ 1-42 monomers spontaneously aggregated to oligomers. We did not find an effect of Aβ 1-42 oligomers on susceptibility to seizures - evoked 1.5 h, 1 week or 3 weeks - after their intracerebral injection. Significance: The lack of effect of Aβ 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 Aβ 1-42 and they are often attributed to subtle differences in the various aggregation forms of the Aβ 1-42 used in different experiments. We confirmed the presence of Aβ 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 Aβ 1-42 oligomers on seizures in AD remains unclear. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Vande Vyver, Daeninck, De Smet, Aourz, Sahu, Engelborghs, Pauwels, De Bundel and Smolders.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu