Collagen VI: Role in synaptic transmission and seizure-related excitability
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Collagen VI : Role in synaptic transmission and seizure-related excitability. / Ramos-Moreno, Tania; Cifra, Alexandra; Litsa, Nikitidou Ledri; Melin, Esbjörn; Ahl, Matilda; Christiansen, Sören H.; Gøtzsche, Casper R.; Cescon, Matilde; Bonaldo, Paolo; van Loo, Karen; Borger, Valeri; Jasper, J. Anink; Becker, Albert; van Vliet, Erwin A.; Aronica, Eleonora; Woldbye, David P.; Kokaia, Merab.
I: Experimental Neurology, Bind 380, 114911, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Collagen VI
T2 - Role in synaptic transmission and seizure-related excitability
AU - Ramos-Moreno, Tania
AU - Cifra, Alexandra
AU - Litsa, Nikitidou Ledri
AU - Melin, Esbjörn
AU - Ahl, Matilda
AU - Christiansen, Sören H.
AU - Gøtzsche, Casper R.
AU - Cescon, Matilde
AU - Bonaldo, Paolo
AU - van Loo, Karen
AU - Borger, Valeri
AU - Jasper, J. Anink
AU - Becker, Albert
AU - van Vliet, Erwin A.
AU - Aronica, Eleonora
AU - Woldbye, David P.
AU - Kokaia, Merab
N1 - Publisher Copyright: © 2024
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Collagen VI
KW - Extracellular matrix
KW - Glutamate release
KW - hippocampus
KW - Status epilepticus
KW - Synaptic plasticity
U2 - 10.1016/j.expneurol.2024.114911
DO - 10.1016/j.expneurol.2024.114911
M3 - Journal article
C2 - 39094767
AN - SCOPUS:85200806111
VL - 380
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
M1 - 114911
ER -
ID: 402284019