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Retigabine, a potassium channel opener, restores thalamocortical neuron functionality in a murine model of autoimmune encephalomyelitis.
Fazio, Luca; Naik, Venu Narayanan; Therpurakal, Rajeevan Narayanan; Gomez Osorio, Fiorella M; Rychlik, Nicole; Ladewig, Julia; Strüber, Michael; Cerina, Manuela; Meuth, Sven G; Budde, Thomas.
Afiliación
  • Fazio L; Department of Neurology, University of Düsseldorf, Düsseldorf, Germany. Electronic address: Luca.Fazio@med.uni-duesseldorf.de.
  • Naik VN; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany. Electronic address: Venu.Narayanannaik@ukmuenster.de.
  • Therpurakal RN; Department of Neurology, University of Düsseldorf, Düsseldorf, Germany. Electronic address: Rajeevan.TherpurakalNarayanan@med.uni-duesseldorf.de.
  • Gomez Osorio FM; Department of Neurology, University of Düsseldorf, Düsseldorf, Germany. Electronic address: FiorellaMaria.GomezOsorio@med.uni-duesseldorf.de.
  • Rychlik N; Institute of Physiology I, University of Münster, Münster, Germany. Electronic address: Nicole.Rychlik@ukmuenster.de.
  • 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 add
  • Strüber M; Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, Goethe University, Frankfurt, Germany. Electronic address: strueber@med.uni-frankfurt.de.
  • Cerina M; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
  • Meuth SG; Department of Neurology, University of Düsseldorf, Düsseldorf, Germany. Electronic address: SvenGuenther.Meuth@med.uni-duesseldorf.de.
  • Budde T; Institute of Physiology I, University of Münster, Münster, Germany. Electronic address: tbudde@uni-muenster.de.
Brain Behav Immun ; 122: 202-215, 2024 Nov.
Article en En | MEDLINE | ID: mdl-39142423
ABSTRACT

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:

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 Kv7 channel opener, on disease outcome.

METHODS:

To resemble the human disease, we focally administered pro-inflammatory cytokines, TNF-α and IFN-γ, in the primary auditory cortex (A1) of MOG35-55 immunized mice. Thereafter, we investigated the impact of the induced inflammatory milieu on afferent thalamocortical (TC) neurons, by performing ex vivo recordings. Moreover, we explored the effect of Kv7 channel modulation with RTG on auditory information processing, using in vivo electrophysiological approaches.

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:

Our results suggest that RTG treatment might robustly mitigate inflammation-induced altered excitability and preserve ascending information processing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenilendiaminas / Tálamo / Carbamatos / Modelos Animales de Enfermedad / Encefalomielitis Autoinmune Experimental / Neuronas Límite: Animals Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenilendiaminas / Tálamo / Carbamatos / Modelos Animales de Enfermedad / Encefalomielitis Autoinmune Experimental / Neuronas Límite: Animals Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos