Retigabine, a potassium channel opener, restores thalamocortical neuron functionality in a murine model of autoimmune encephalomyelitis.

Cytokines Inflammation KCNQ Multiple sclerosis Retigabine Thalamus

Journal

Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478

Informations de publication

Date de publication:
12 Aug 2024
Historique:
received: 30 10 2023
revised: 07 08 2024
accepted: 10 08 2024
medline: 15 8 2024
pubmed: 15 8 2024
entrez: 14 8 2024
Statut: aheadofprint

Résumé

Multiple Sclerosis (MS) is an autoimmune neurodegenerative disease, whose primary hallmark is the occurrence of inflammatory lesions in white and grey matter structures. Increasing evidence in MS patients and respective murine models reported an impaired ionic homeostasis driven by inflammatory-demyelination, thereby profoundly affecting signal propagation. However, the impact of a focal inflammatory lesion on single-cell and network functionality has hitherto not been fully elucidated. In this study, we sought to determine the consequences of a localized cortical inflammatory lesion on the excitability and firing pattern of thalamic neurons in the auditory system. Moreover, we tested the neuroprotective effect of Retigabine (RTG), a specific K To resemble the human disease, we focally administered pro-inflammatory cytokines, TNF-α and IFN-γ, in the primary auditory cortex (A1) of MOG Our results revealed that a cortical inflammatory lesion profoundly affected the excitability and firing pattern of neighboring TC neurons. Noteworthy, RTG restored control-like values and TC tonotopic mapping. Our results suggest that RTG treatment might robustly mitigate inflammation-induced altered excitability and preserve ascending information processing.

Sections du résumé

BACKGROUND BACKGROUND
Multiple Sclerosis (MS) is an autoimmune neurodegenerative disease, whose primary hallmark is the occurrence of inflammatory lesions in white and grey matter structures. Increasing evidence in MS patients and respective murine models reported an impaired ionic homeostasis driven by inflammatory-demyelination, thereby profoundly affecting signal propagation. However, the impact of a focal inflammatory lesion on single-cell and network functionality has hitherto not been fully elucidated.
OBJECTIVES OBJECTIVE
In this study, we sought to determine the consequences of a localized cortical inflammatory lesion on the excitability and firing pattern of thalamic neurons in the auditory system. Moreover, we tested the neuroprotective effect of Retigabine (RTG), a specific K
METHODS METHODS
To resemble the human disease, we focally administered pro-inflammatory cytokines, TNF-α and IFN-γ, in the primary auditory cortex (A1) of MOG
RESULTS RESULTS
Our results revealed that a cortical inflammatory lesion profoundly affected the excitability and firing pattern of neighboring TC neurons. Noteworthy, RTG restored control-like values and TC tonotopic mapping.
CONCLUSION CONCLUSIONS
Our results suggest that RTG treatment might robustly mitigate inflammation-induced altered excitability and preserve ascending information processing.

Identifiants

pubmed: 39142423
pii: S0889-1591(24)00546-4
doi: 10.1016/j.bbi.2024.08.023
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Luca Fazio (L)

Department of Neurology, University of Düsseldorf, Düsseldorf, Germany. Electronic address: Luca.Fazio@med.uni-duesseldorf.de.

Venu Narayanan Naik (VN)

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany. Electronic address: Venu.Narayanannaik@ukmuenster.de.

Rajeevan Narayanan Therpurakal (RN)

Department of Neurology, University of Düsseldorf, Düsseldorf, Germany. Electronic address: Rajeevan.TherpurakalNarayanan@med.uni-duesseldorf.de.

Fiorella M Gomez Osorio (FM)

Department of Neurology, University of Düsseldorf, Düsseldorf, Germany. Electronic address: FiorellaMaria.GomezOsorio@med.uni-duesseldorf.de.

Nicole Rychlik (N)

Institute of Physiology I, University of Münster, Münster, Germany. Electronic address: Nicole.Rychlik@ukmuenster.de.

Julia Ladewig (J)

Department of Translational Brain Research, Central Institute of Mental Health (ZI), University of Heidelberg/Medical Faculty Mannheim, Germany; HITBR Hector Institute for Translational Brain Research gGmbH, Mannheim, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: Julia.Ladewig@zi-mannheim.de.

Michael Strüber (M)

Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, Goethe University, Frankfurt, Germany. Electronic address: strueber@med.uni-frankfurt.de.

Manuela Cerina (M)

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.

Sven G Meuth (SG)

Department of Neurology, University of Düsseldorf, Düsseldorf, Germany. Electronic address: SvenGuenther.Meuth@med.uni-duesseldorf.de.

Thomas Budde (T)

Institute of Physiology I, University of Münster, Münster, Germany. Electronic address: tbudde@uni-muenster.de.

Classifications MeSH