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

Ramos-Moreno, Tania LU orcid ; Cifra, Alexandra ; Litsa, Nikitidou Ledri LU ; Melin, Esbjörn LU orcid ; Ahl, Matilda LU ; Christiansen, Sören H. ; Gøtzsche, Casper R. ; Cescon, Matilde ; Bonaldo, Paolo and van Loo, Karen , et al. (2024) In Experimental Neurology 380.
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
Collagen VI, Extracellular matrix, Glutamate release, hippocampus, Status epilepticus, Synaptic plasticity
in
Experimental Neurology
volume
380
article number
114911
publisher
Elsevier
external identifiers
  • pmid:39094767
  • scopus:85200806111
ISSN
0014-4886
DOI
10.1016/j.expneurol.2024.114911
language
English
LU publication?
yes
id
80af1788-2256-454e-b307-19760b4b6431
date added to LUP
2024-09-06 13:12:00
date last changed
2024-09-07 02:42:00
@article{80af1788-2256-454e-b307-19760b4b6431,
  abstract     = {{<p>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.</p>}},
  author       = {{Ramos-Moreno, Tania and Cifra, Alexandra and Litsa, Nikitidou Ledri and Melin, Esbjörn and Ahl, Matilda and Christiansen, Sören H. and Gøtzsche, Casper R. and Cescon, Matilde and Bonaldo, Paolo and van Loo, Karen and Borger, Valeri and Jasper, J. Anink and Becker, Albert and van Vliet, Erwin A. and Aronica, Eleonora and Woldbye, David P. and Kokaia, Merab}},
  issn         = {{0014-4886}},
  keywords     = {{Collagen VI; Extracellular matrix; Glutamate release; hippocampus; Status epilepticus; Synaptic plasticity}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Experimental Neurology}},
  title        = {{Collagen VI : Role in synaptic transmission and seizure-related excitability}},
  url          = {{http://dx.doi.org/10.1016/j.expneurol.2024.114911}},
  doi          = {{10.1016/j.expneurol.2024.114911}},
  volume       = {{380}},
  year         = {{2024}},
}