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

Year: 2019

Type: article

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.

Source: Brain Sciences

DOI: 10.3390/brainsci9120361

Authors: Michal Bajo, Reesha R. Patel, David M. Hedges, Florence P. Varodayan, Roman Vlkolinsky, Tony D. Davis, Michael D. Burkart, Yuri A. Blednov, Marisa Roberto

Institutions: Scripps Research Institute, University of California San Diego, The University of Texas at Austin

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,418

Funders: Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute of General Medical Sciences

OpenAlex ID: W2993905113