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Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala

Myeloid differentiation primary response protein (MyD88) is a critical neuroimmune adaptor protein in TLR (Toll-like receptor) and IL-1R (Interleukin-1 receptor) signaling complexes. These two pro-inflammatory families play an important role in the neurobiology of alcohol use disorder, specifically...

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Autores principales: Bajo, Michal, Patel, Reesha R., Hedges, David M., Varodayan, Florence P., Vlkolinsky, Roman, Davis, Tony D., Burkart, Michael D., Blednov, Yuri A., Roberto, Marisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956324/
https://www.ncbi.nlm.nih.gov/pubmed/31817854
http://dx.doi.org/10.3390/brainsci9120361
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author Bajo, Michal
Patel, Reesha R.
Hedges, David M.
Varodayan, Florence P.
Vlkolinsky, Roman
Davis, Tony D.
Burkart, Michael D.
Blednov, Yuri A.
Roberto, Marisa
author_facet Bajo, Michal
Patel, Reesha R.
Hedges, David M.
Varodayan, Florence P.
Vlkolinsky, Roman
Davis, Tony D.
Burkart, Michael D.
Blednov, Yuri A.
Roberto, Marisa
author_sort Bajo, Michal
collection PubMed
description Myeloid differentiation primary response protein (MyD88) is a critical neuroimmune adaptor protein in TLR (Toll-like receptor) and IL-1R (Interleukin-1 receptor) signaling complexes. These two pro-inflammatory families play an important role in the neurobiology of alcohol use disorder, specifically MyD88 regulates ethanol drinking, ethanol-induced sedation, and ethanol-induced deficits in motor coordination. In this study, we examined the role of MyD88 in mediating the effects of IL-1β and ethanol on GABAergic transmission in the central amygdala (CeA) of male mice using whole-cell patch-clamp recordings in combination with pharmacological (AS-1, a mimetic that prevents MyD88 recruitment by IL-1R) and genetic (Myd88 knockout mice) approaches. We demonstrate through both approaches that IL-1β and ethanol’s modulatory effects at CeA GABA synapses are not dependent on MyD88. Myd88 knockout potentiated IL-1β’s actions in reducing postsynaptic GABA(A) receptor function. Pharmacological inhibition of MyD88 modulates IL-1β’s action at CeA GABA synapses similar to Myd88 knockout mice. Additionally, ethanol-induced CeA GABA release was greater in Myd88 knockout mice compared to wildtype controls. Thus, MyD88 is not essential to IL-1β or ethanol regulation of CeA GABA synapses but plays a role in modulating the magnitude of their effects, which may be a potential mechanism by which it regulates ethanol-related behaviors.
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spelling pubmed-69563242020-01-23 Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala Bajo, Michal Patel, Reesha R. Hedges, David M. Varodayan, Florence P. Vlkolinsky, Roman Davis, Tony D. Burkart, Michael D. Blednov, Yuri A. Roberto, Marisa Brain Sci Article Myeloid differentiation primary response protein (MyD88) is a critical neuroimmune adaptor protein in TLR (Toll-like receptor) and IL-1R (Interleukin-1 receptor) signaling complexes. These two pro-inflammatory families play an important role in the neurobiology of alcohol use disorder, specifically MyD88 regulates ethanol drinking, ethanol-induced sedation, and ethanol-induced deficits in motor coordination. In this study, we examined the role of MyD88 in mediating the effects of IL-1β and ethanol on GABAergic transmission in the central amygdala (CeA) of male mice using whole-cell patch-clamp recordings in combination with pharmacological (AS-1, a mimetic that prevents MyD88 recruitment by IL-1R) and genetic (Myd88 knockout mice) approaches. We demonstrate through both approaches that IL-1β and ethanol’s modulatory effects at CeA GABA synapses are not dependent on MyD88. Myd88 knockout potentiated IL-1β’s actions in reducing postsynaptic GABA(A) receptor function. Pharmacological inhibition of MyD88 modulates IL-1β’s action at CeA GABA synapses similar to Myd88 knockout mice. Additionally, ethanol-induced CeA GABA release was greater in Myd88 knockout mice compared to wildtype controls. Thus, MyD88 is not essential to IL-1β or ethanol regulation of CeA GABA synapses but plays a role in modulating the magnitude of their effects, which may be a potential mechanism by which it regulates ethanol-related behaviors. MDPI 2019-12-07 /pmc/articles/PMC6956324/ /pubmed/31817854 http://dx.doi.org/10.3390/brainsci9120361 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bajo, Michal
Patel, Reesha R.
Hedges, David M.
Varodayan, Florence P.
Vlkolinsky, Roman
Davis, Tony D.
Burkart, Michael D.
Blednov, Yuri A.
Roberto, Marisa
Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala
title Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala
title_full Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala
title_fullStr Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala
title_full_unstemmed Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala
title_short Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala
title_sort role of myd88 in il-1β and ethanol modulation of gabaergic transmission in the central amygdala
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956324/
https://www.ncbi.nlm.nih.gov/pubmed/31817854
http://dx.doi.org/10.3390/brainsci9120361
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