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© 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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 GABAA 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.

Details

Title
Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala
Author
Bajo, Michal 1 ; Patel, Reesha R 1 ; Hedges, David M 1 ; Varodayan, Florence P 1 ; Vlkolinsky, Roman 1 ; Davis, Tony D 2   VIAFID ORCID Logo  ; Burkart, Michael D 2 ; Blednov, Yuri A 3 ; Roberto, Marisa 1 

 Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA[email protected] (D.M.H.); [email protected] (F.P.V.); [email protected] (R.V.); [email protected] (M.R.) 
 Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA; [email protected] (T.D.D.); [email protected] (M.D.B.) 
 Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA; [email protected] 
First page
361
Publication year
2019
Publication date
2019
Publisher
MDPI AG
e-ISSN
20763425
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2535176076
Copyright
© 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.