May 7, 2020

Gelatinase Biosensor Reports Cellular Remodeling During Epileptogenesis

Frontiers in Synaptic Neuroscience
Nathalie BouquierJulie Perroy

Abstract

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 ...Continue Reading

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Mentioned in this Paper

Matrix Metalloproteinase 9
Matrix Metalloproteinase 2
CA1 Field
MMP9
Brain Injuries
Epilepsy, Temporal Lobe
Cell-Penetrating Peptides
5-carboxytetramethylrhodamine succinimidyl ester
Acpp protein, mouse
Neoplasms

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