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Gelatinase Biosensor Reports Cellular Remodeling During Epileptogenesis

Epileptogenesis is the gradual process responsible for converting a healthy brain into an epileptic brain. This process can be triggered by a wide range of factors, including brain injury or tumors, infections, and status epilepticus. Epileptogenesis results in aberrant synaptic plasticity, neuroinf...

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Autores principales: Bouquier, Nathalie, Girard, Benoit, Aparicio Arias, Juri, Fagni, Laurent, Bertaso, Federica, Perroy, Julie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186352/
https://www.ncbi.nlm.nih.gov/pubmed/32372941
http://dx.doi.org/10.3389/fnsyn.2020.00015
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author Bouquier, Nathalie
Girard, Benoit
Aparicio Arias, Juri
Fagni, Laurent
Bertaso, Federica
Perroy, Julie
author_facet Bouquier, Nathalie
Girard, Benoit
Aparicio Arias, Juri
Fagni, Laurent
Bertaso, Federica
Perroy, Julie
author_sort Bouquier, Nathalie
collection PubMed
description Epileptogenesis is the gradual process responsible for converting a healthy brain into an epileptic brain. This process can be triggered by a wide range of factors, including brain injury or tumors, infections, and status epilepticus. Epileptogenesis results in aberrant synaptic plasticity, neuroinflammation and seizure-induced cell death. As Matrix Metalloproteinases (MMPs) play a crucial role in cellular plasticity by remodeling the extracellular matrix (ECM), gelatinases (MMP-2 and MMP-9) were recently highlighted as key players in epileptogenesis. In this work, we engineered a biosensor to report in situ gelatinase activity in a model of epileptogenesis. This biosensor encompasses a gelatinase-sensitive activatable cell penetrating peptide (ACPP) coupled to a TAMRA fluorophore, allowing fluorescence uptake in cells displaying endogenous gelatinase activities. In a preclinical mouse model of temporal lobe epilepsy (TLE), the intrahippocampal kainate injection, ACPPs revealed a localized distribution of gelatinase activities, refining temporal cellular changes during epileptogenesis. The activity was found particularly but not only in the ipsilateral hippocampus, starting from the CA1 area and spreading to dentate gyrus from the early stages throughout chronic epilepsy, notably in neurons and microglial cells. Thus, our work shows that ACPPs are suitable molecular imaging probes for detecting the spatiotemporal pattern of gelatinase activity during epileptogenesis, suggesting their possible use as vectors to target cellular reactive changes with treatment for epileptogenesis.
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spelling pubmed-71863522020-05-05 Gelatinase Biosensor Reports Cellular Remodeling During Epileptogenesis Bouquier, Nathalie Girard, Benoit Aparicio Arias, Juri Fagni, Laurent Bertaso, Federica Perroy, Julie Front Synaptic Neurosci Neuroscience Epileptogenesis is the gradual process responsible for converting a healthy brain into an epileptic brain. This process can be triggered by a wide range of factors, including brain injury or tumors, infections, and status epilepticus. Epileptogenesis results in aberrant synaptic plasticity, neuroinflammation and seizure-induced cell death. As Matrix Metalloproteinases (MMPs) play a crucial role in cellular plasticity by remodeling the extracellular matrix (ECM), gelatinases (MMP-2 and MMP-9) were recently highlighted as key players in epileptogenesis. In this work, we engineered a biosensor to report in situ gelatinase activity in a model of epileptogenesis. This biosensor encompasses a gelatinase-sensitive activatable cell penetrating peptide (ACPP) coupled to a TAMRA fluorophore, allowing fluorescence uptake in cells displaying endogenous gelatinase activities. In a preclinical mouse model of temporal lobe epilepsy (TLE), the intrahippocampal kainate injection, ACPPs revealed a localized distribution of gelatinase activities, refining temporal cellular changes during epileptogenesis. The activity was found particularly but not only in the ipsilateral hippocampus, starting from the CA1 area and spreading to dentate gyrus from the early stages throughout chronic epilepsy, notably in neurons and microglial cells. Thus, our work shows that ACPPs are suitable molecular imaging probes for detecting the spatiotemporal pattern of gelatinase activity during epileptogenesis, suggesting their possible use as vectors to target cellular reactive changes with treatment for epileptogenesis. Frontiers Media S.A. 2020-04-21 /pmc/articles/PMC7186352/ /pubmed/32372941 http://dx.doi.org/10.3389/fnsyn.2020.00015 Text en Copyright © 2020 Bouquier, Girard, Aparicio Arias, Fagni, Bertaso and Perroy. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Bouquier, Nathalie
Girard, Benoit
Aparicio Arias, Juri
Fagni, Laurent
Bertaso, Federica
Perroy, Julie
Gelatinase Biosensor Reports Cellular Remodeling During Epileptogenesis
title Gelatinase Biosensor Reports Cellular Remodeling During Epileptogenesis
title_full Gelatinase Biosensor Reports Cellular Remodeling During Epileptogenesis
title_fullStr Gelatinase Biosensor Reports Cellular Remodeling During Epileptogenesis
title_full_unstemmed Gelatinase Biosensor Reports Cellular Remodeling During Epileptogenesis
title_short Gelatinase Biosensor Reports Cellular Remodeling During Epileptogenesis
title_sort gelatinase biosensor reports cellular remodeling during epileptogenesis
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186352/
https://www.ncbi.nlm.nih.gov/pubmed/32372941
http://dx.doi.org/10.3389/fnsyn.2020.00015
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