The Regulatory Role of miRNAs in Ethanol-induced TLR4 Activation and Neuroinflammation
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THE PATHOBIOLOGY OF ALCOHOL CONSUMPTION (P MOLINA AND M RONIS, SECTION EDITORS)
The Regulatory Role of miRNAs in Ethanol-induced TLR4 Activation and Neuroinflammation María Pascual 1,2 & Juan R. Ureña-Peralta 1 & Consuelo Guerri 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Alcohol is a neurotoxic compound and its abuse can induce brain damage and neurodegeneration. Evidence from the last decade demonstrates the critical role of the innate immune system in neuroinflammation associated with alcohol abuse. In this review, we discuss the role of miRNAs as regulators of immune Toll-like receptors (TLR4), the neuroimmune response associated with alcohol abuse, and the importance of glial extracellular vesicles in amplifying neuroinflammation. Recent Findings Current studies demonstrate the role of glial extracellular vesicles/exosomes in extending neuroinflammation, and the importance of miRNAs as key regulators of different biological functions. However, dysregulation of miRNAs also participates in neurological and neurodegenerative diseases associated with neuroinflammation. Recent findings indicate the possibility of circulating miRNAs being used as biomarkers to screen neurological and neuroinflammatory disorders as early diagnosis and therapy. Summary This article highlights the role of miRNAs in regulating neuroinflammation associated with alcohol abuse and the importance of glial extracellular vesicles/exosomes in extending neuroinflammation. Keywords Alcohol abuse . Neuroinflammation . Toll-like receptors . miRNAs . Extracellular vesicles/exosomes
Introduction It is well-established that alcohol is a neurotoxic compound and alcohol abuse can induce important morphological, structural, and molecular changes in the brain [1]. Excessive chronic alcohol consumption impairs white matter fibers and disrupts the transmission of neuronal signals in both human and experimental animals [2, 3]. Postmortem studies of patients with chronic alcohol abuse have confirmed demyelination in callosal, supratentorial, and infratentorial white matter fibers (e.g., [4]) and microtubule disruption [5–7]. It is noteworthy This article is part of the Topical Collection on The Pathobiology of Alcohol Consumption * Consuelo Guerri [email protected] 1
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that transcallosal white matter alterations have been associated with cognitive and motor impairments [2]. Findings from the last decade have also shown that binge drinkinginadolescence,astageofbrainmaturation,cancausefunctional andstructuralchangesinthehippocampusandinthepre-prefrontal cortex that persist into adulthood (see rev., [8]). This pattern of drinking alters synaptic plasticity and impairs myelin fibers and the proportion of immature synaptic connections in the prefrontal cortex,whichcontributestocognitiveandmemorydeficitsinadulthood [9]. Preclinical and clinical studies have also indicated that ethanol exposure in early adolescence leads to heightened anxiety and higher alcohol intake in adulthood [10–12]. The mechanism of e
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