ESR 13 - Armand Blondiaux

Hosted at LIN

ESR7 round

Armand studied neurosciences and biostatistics at the University of Montpellier, France. During hisstudies he worked in different laboratories on various topics. he mainly focused on neurosciences working on pharmacology of attention deficit - hyperactivity disorder drugs in De Monfort University (UK), molecular biology of the auditory cells in the Institute for Neuroscience of Montpellier (France) and genetics of autism in Trinity College Dublin (Ireland).

He joined ECMED to work at the Leibniz Institute for Neurobiolgy on the role of the lectican protein-family in epilepsy and epileptogenesis."




Integrity of the lectican-based ECM and epilepsy

Background

Epileptic seizures are strong, pathogenic discharges of neuronal networks. The extracellular matrix (ECM) of the brain stabilizes neuronal networks and is an important extracellular factor controlling various forms of synaptic plasticity such as long-term potentiation (LTP), short-term plasticity and structural plasticity. On the systemic level, local ECM removal leads to altered learning performance in rodents. Thus, an intact ECM is a prerequisite for normal brain function. Interestingly, strong neuronal activity as observed during epileptiform discharges leads to altered ECM composition and the release and activation of ECM processing proteases. 

Objectives

  • To evaluate the role of ECM components in epileptogenesis and maintenance of status epilepticus. 
  • To evaluate the role of ECM-modifying proteases in epilepsy. 
  • Study morphological and molecular parameters after seizures in mice lacking components of the ECM or MMPs. 
  • Interfering with ECM and protease activity alterations to suppress seizure phenotypes and develop potential treatment strategies.

Approach

We will study the threshold, onset and frequency of seizures using a post-SE (induced by dentate gyrus stimulation) mouse model in wild types and knockouts of the ECM molecules brevican, neurocan, tenascin-R and aggrecan as well as of ADAMTS-4, the major ECM degrading enzyme. In order to analyse morphological hallmarks after SE, knockout mice will be crossed with mice expressing EGFP in a small subset of neurons and hippocampal slices will be subjected to confocal and/or two-photon imaging to analyse dendritic complexity, spine morphology and density 10-20 days after SE. In addition the appearance of identifiable proteolytic fragments of selected components of the ECM will be quantified by western blotting in order to investigate the role of proteolysis during epileptogenesis and in SE. In dissociated hippocampal cultures from wild type and knockout animals we will further measure changes in the abundance of synaptic proteins after different time points of network disinhibition, which induces epileptiform discharges, in presence and absence of MMP inhibitors. Gained knowledge will be applied to develop rescue strategies to counteract morphological and pathological phenotypes in knockout animals. 

Collaborations

The post-holder will have the opportunity to visit other laboratories within the consortium in order to acquire additional skills. These collaborations/secondments will be arranged in response to developments and new challenges faced during the project.

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