Linking epileptic phenotypes and neural extracellular matrix remodeling signatures in mouse models of epilepsy

Blondiaux A, Jia S, Annamneedi A, Çalışkan G, Nebel J, Montenegro-Venegas C, Wykes RC, Fejtová A, Walker MC, Stork O, Gundelfinger ED, Dityatev A, Seidenbecher CI (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Neurobiology of Disease Elsevier

Book Volume: 188

Article Number: 106324

DOI: 10.1016/j.nbd.2023.106324

Abstract

Epilepsies are multifaceted neurological disorders characterized by abnormal brain activity, e.g. caused by imbalanced synaptic excitation and inhibition. The neural extracellular matrix (ECM) is dynamically modulated by physiological and pathophysiological activity and critically involved in controlling the brain's excitability. We used different epilepsy models, i.e. mice lacking the presynaptic scaffolding protein Bassoon at excitatory, inhibitory or all synapse types as genetic models for rapidly generalizing early-onset epilepsy, and intra-hippocampal kainate injection, a model for acquired temporal lobe epilepsy, to study the relationship between epileptic seizures and ECM composition. Electroencephalogram recordings revealed Bassoon deletion at excitatory or inhibitory synapses having diverse effects on epilepsy-related phenotypes. While constitutive Bsn mutants and to a lesser extent GABAergic neuron-specific knockouts (Bsn^Dlx5/6cKO) displayed severe epilepsy with more and stronger seizures than kainate-injected animals, mutants lacking Bassoon solely in excitatory forebrain neurons (Bsn^Emx1cKO) showed only mild impairments. By semiquantitative immunoblotting and immunohistochemistry we show model-specific patterns of neural ECM remodeling, and we also demonstrate significant upregulation of the ECM receptor CD44 in null and Bsn^Dlx5/6cKO mutants. ECM-associated WFA-binding chondroitin sulfates were strongly augmented in seizure models. Strikingly, Brevican, Neurocan, Aggrecan and link proteins Hapln1 and Hapln4 levels reliably predicted seizure properties across models, suggesting a link between ECM state and epileptic phenotype.

Authors with CRIS profile

Anna Fejtová Professur für Molekulare Psychiatrie

Involved external institutions

Leibniz-Institut für Neurobiologie (LIN)

Germany (DE) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)

Germany (DE) Otto-von-Guericke-Universität Magdeburg

Germany (DE) University College London (UCL)

United Kingdom (GB)

How to cite

APA:

Blondiaux, A., Jia, S., Annamneedi, A., Çalışkan, G., Nebel, J., Montenegro-Venegas, C.,... Seidenbecher, C.I. (2023). Linking epileptic phenotypes and neural extracellular matrix remodeling signatures in mouse models of epilepsy. Neurobiology of Disease, 188. https://doi.org/10.1016/j.nbd.2023.106324

MLA:

Blondiaux, Armand, et al. "Linking epileptic phenotypes and neural extracellular matrix remodeling signatures in mouse models of epilepsy." Neurobiology of Disease 188 (2023).

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