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 -