Collagen VI: Role in synaptic transmission and seizure-related excitability.

Autor: Ramos-Moreno T; Epilepsy Centre, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden., Cifra A; Epilepsy Centre, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden., Litsa NL; Epilepsy Centre, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden., Melin E; Epilepsy Centre, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden., Ahl M; Epilepsy Centre, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden., Christiansen SH; Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, 1165 Copenhagen, Denmark., Gøtzsche CR; Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, 1165 Copenhagen, Denmark., Cescon M; Department of Molecular Medicine, University of Padova, I-35131 Padova, Italy., Bonaldo P; Department of Molecular Medicine, University of Padova, I-35131 Padova, Italy., van Loo K; Institut für Neuropathologie, Universitätsklinikum Bonn, Bonn, Germany., Borger V; Institut für Neuropathologie, Universitätsklinikum Bonn, Bonn, Germany., Jasper JA; Amsterdam UMC, Location University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands., Becker A; Institut für Neuropathologie, Universitätsklinikum Bonn, Bonn, Germany., van Vliet EA; Amsterdam UMC, Location University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands; Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, the Netherlands., Aronica E; Amsterdam UMC, Location University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands; Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, the Netherlands., Woldbye DP; Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, 1165 Copenhagen, Denmark., Kokaia M; Epilepsy Centre, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden. Electronic address: Merab.Kokaia@med.lu.se.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2024 Oct; Vol. 380, pp. 114911. Date of Electronic Publication: 2024 Jul 31.
DOI: 10.1016/j.expneurol.2024.114911
Abstrakt: Collagen VI (Col-VI) is an extracellular matrix protein primarily known for its bridging role in connective tissues that has been suggested to play a neuroprotective role. In the present study we report increased mRNA and protein expression of Col-VI in the hippocampus and cortex at a late stage of epileptogenesis in a post-status epilepticus (SE) model of epilepsy and in brain tissue from patients with epilepsy. We further present a novel finding that exposure of mouse hippocampal slices to Col-VI augments paired-pulse facilitation in Schaffer collateral-CA1 excitatory synapses indicating decreased release probability of glutamate. In line with this finding, lack of Col-VI expression in the knock-out mice show paired-pulse depression in these synapses, suggesting increased release probability of glutamate. In addition, we observed dynamic changes in Col-VI blood plasma levels in rats after Kainate-induced SE, and increased levels of Col-VI mRNA and protein in autopsy or postmortem brain of humans suffering from epilepsy. Thus, our data indicate that elevated levels of ColVI following seizures leads to attenuated glutamatergic transmission, ultimately resulting in less overall network excitability. Presumably, increased Col-VI may act as part of endogenous compensatory mechanism against enhanced excitability during epileptogenic processes in the hippocampus, and could be further investigated as a potential functional biomarker of epileptogenesis, and/or a novel target for therapeutic intervention.
Competing Interests: Declaration of competing interest The authors declare no competing financial interests.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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