Toll‐like receptor 4 participates in the myelin disruptions associated with chronic alcohol abuse

Alfonso-Loeches, Silvia; Pascual, Marı́a; Gómez‐Pinedo, Ulises; Pascual-Lucas, Maya; Renau‐Piqueras, Jaime

doi:10.1002/glia.22327

Cited by 96 publications

(98 citation statements)

References 54 publications

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“…Dysregulated ubiquitination contributes to the development of Alzheimer's disease and other neurodegenerative disorders [for review, see (8)], and is associated with demyelination and white matter degeneration (123). Myelin degradation has been associated with ethanol abuse (2,28,68), but to our knowledge males and females have not been examined separately. Though complex, TNF production has been associated with enhanced demyelination (66), while Tgfb1 expression reduces demyelination (33).…”

Section: Discussionmentioning

confidence: 99%

Astrocyte Dysfunction Induced by Alcohol in Females but Not Males

et al. 2015

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Chronic alcohol abuse is associated with brain damage in a sex-specific fashion, but the mechanisms involved are poorly described and remain controversial. Previous results have suggested that astrocyte gene expression is influenced by ethanol intoxication and during abstinence in vivo. Here, bioinformatic analysis of astrocyte-enriched ethanol-regulated genes in vivo revealed ubiquitin pathways as an ethanol target, but with sexually dimorphic cytokine signaling and changes associated with brain aging in females and not males. Consistent with this result, astrocyte activation was observed after exposure in female but not male animals, with reduced S100β levels in the anterior cingulate cortex and increased GFAP(+) cells in the hippocampus. In primary culture, the direct effects of chronic ethanol exposure followed by recovery on sex-specific astrocyte function were examined. Male astrocyte responses were consistent with astrocyte deactivation with reduced GFAP expression during ethanol exposure. In contrast, female astrocytes exhibited increased expression of Tnf, reduced expression of the neuroprotective cytokine Tgfb1, disrupted bioenergetics and reduced excitatory amino acid uptake following exposure or recovery. These results indicate widespread astrocyte dysfunction in ethanol-exposed females and suggest a mechanism that may underlie increased vulnerability to ethanol-induced neurotoxicity in females.

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Section: Discussionmentioning

confidence: 99%

Astrocyte Dysfunction Induced by Alcohol in Females but Not Males

et al. 2015

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“…TLR4 receptors are constitutively expressed on microglia, making microglia a key component of drug-induced neuroimmune activation (Alfonso-Loeches & Guerri, 2011; Schwarz & Bilbo, 2013). More recent studies by Guerri’s laboratory have found that TLR4 receptors are integral to ethanol-induced dopamine release (Alfonso-Loeches & Guerri, 2011), damage to white matter (Alfonso-Loeches et al, 2012), and other pathologies associated with chronic ethanol-induced changes in brain (Pascual et al, 2011). In culture, ethanol treatment increases innate immune gene expression in a time-dependent fashion mimicking responses to LPS or IL-1β administration, although ethanol induces a much smaller response (Crews et al, 2013).…”

Section: Alcohol Neuroimmune Signaling and Neurodegenerationmentioning

confidence: 99%

Neuroimmune Basis of Alcoholic Brain Damage

Crews

Vetreno

2014

International Review of Neurobiology

133

111

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Alcohol-induced brain damage likely contributes to the dysfunctional poor decisions associated with alcohol dependence. Human alcoholics have a global loss of brain volume that is most severe in the frontal cortex. Neuroimmune gene induction by binge drinking increases neurodegeneration through increased oxidative stress, particularly NADPH oxidase-induced oxidative stress. In addition, HMGB1-TLR4 and innate immune NF-κB target genes are increased leading to persistent and sensitized neuroimmune responses to ethanol and other agents that release HMGB1 or directly stimulate TLR receptors and/or NMDA receptors. Neuroimmune signaling and glutamate excitotoxicity are linked to alcoholic neurodegeneration. Models of adolescent alcohol abuse lead to significant frontal cortical degeneration and show the most severe loss of hippocampal neurogenesis. Adolescence is a period of high risk for ethanol-induced neurodegeneration and alterations in brain structure, gene expression, and maturation of adult phenotypes. Together, these findings support the hypothesis that adolescence is a period of risk for persistent and long-lasting increases in brain neuroimmune gene expression that promote persistent and long-term increases in alcohol consumption, neuroimmune gene induction, and neurodegeneration that we find associated with alcohol use disorders.

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“…Alcohol also has a genotoxic effect [16]. In the case of chronic alcohol abuse, white matter decreases as a result of inhibition of the remyelination and apoptosis of glial cells proportional to the quantity of alcohol consumed [17]. In comparative studies of alcohol addicted patients with and without thiamine deficiency, atrophy was more pronounced both regionally and globally in vitamin-deficient patients.…”

Section: Atrophymentioning

confidence: 99%

The Whole Spectrum of Alcohol-Related Changes in the CNS: Practical MR and CT Imaging Guidelines for Daily Clinical Use

Keil

Greschus

Schneider

et al. 2015

Fortschr Röntgenstr

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Alcohol addiction is the most common drug addiction. Alcohol passes both the placenta as well as the blood-brain barrier and is in multiple ways neurotoxic. Liver diseases and other systemic alcohol-related diseases cause secondary damage to the CNS.?Especially in adolescents, even a single episode of severe alcohol intoxication (?binge drinking?) may result in life-threatening neurological consequences. Alcohol-related brain and spinal cord diseases derive from multiple causes including impairment of the cellular metabolism, often aggravated by hypovitaminosis, altered neurotransmission, myelination and synaptogenesis as well as alterations in gene expression. Modern radiological diagnostics, MRI in particular, can detect the resulting alterations in the CNS with a high sensitivity. Morphological aspects often strongly correlate with clinical symptoms of the patient. It is less commonly known that many diseases considered as ?typically alcohol-related?, such as Wernicke?s encephalopathy, are to a large extent not alcohol-induced. Visible CNS alterations are thus non-pathognomonic and demand careful evaluation of differential diagnoses. This review article elucidates the pathogenesis, clinical aspects and radiological image features of the most common alcohol-related CNS diseases and their differential diagnoses. Key Points: ??Alcohol-associated changes in the CNS are common and radiologically assessable. ??They are often subtle and allow multiple differential diagnoses besides alcohol consumption. ??Knowledge of clinical exams and lab results is crucial for diagnostic accuracy. Citation Format: ??Keil VC, Greschus S, Schneider C et?al. The Whole Spectrum of Alcohol-Related Changes in the CNS: Practical MR and CT Imaging Guidelines for Daily Clinical Use. Fortschr R?ntgenstr 2015; 187: 1073???1083

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Toll‐like receptor 4 participates in the myelin disruptions associated with chronic alcohol abuse

Cited by 96 publications

References 54 publications

Astrocyte Dysfunction Induced by Alcohol in Females but Not Males

Astrocyte Dysfunction Induced by Alcohol in Females but Not Males

Neuroimmune Basis of Alcoholic Brain Damage

The Whole Spectrum of Alcohol-Related Changes in the CNS: Practical MR and CT Imaging Guidelines for Daily Clinical Use

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