{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:54:07Z","timestamp":1792637647723,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,3,19]],"date-time":"2012-03-19T00:00:00Z","timestamp":1332115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alcohol abuse and alcoholism can cause brain damage, loss of white matter, myelin fiber disruption, and even neuronal injury. The underlying mechanisms of these alterations remain elusive. We have shown that chronic ethanol intake, by activating glial toll\u2010like receptor 4 (TLR4) receptors, triggers the production of inflammatory mediators and can cause brain damage. Because neuroinflammation may be associated with demyelination and neuronal damage, we evaluate whether the ethanol\u2010induced TLR4\u2010dependent proinflammatory environment in the brain could be involved in the myelin disruptions observed in alcoholics. Using brains from wild\u2010type (WT) and TLR4 knockout (KO, TLR4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice, we demonstrate that chronic ethanol treatment downregulated proteins involved in myelination [proteolipid protein (PLP), myelin basic protein (MBP), myelin\u2010oligodendrocyte glycoprotein, 2,3\u2010cyclic\u2010nucleotide\u20103\u2010phosphodiesterase, and myelin\u2010associated glycoprotein], while increased chondroitin sulfate proteoglycan NG2 (NG2)\u2010proteoglycan in several brain regions of ethanol\u2010treated WT mice. The immunohistochemistry analysis also revealed that ethanol\u2010treatment\u2010altered myelin morphology reduced the number of MBP\u2010positive fibers and caused oligodendrocyte death, as demonstrated by an increase in caspase\u20103\u2010positive oligodendrocytes. The\n                    <jats:italic>in vivo<\/jats:italic>\n                    imaging system further confirmed that chronic ethanol intake markedly reduced the PLP in WT mice. Most myelin alterations were not observed in brains from ethanol\u2010treated TLR4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Electron microscopy studies revealed that although 41\u201347% of axons showed myelin sheath disarrangements in the cerebral cortex and corpus callosum of WT ethanol\u2010treated mice, respectively, small focal fiber disruptions were noticed in these brain areas of ethanol\u2010treated TLR4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. In summary, the present results suggest that ethanol\u2010induced neuroinflammation might be involved in myelin disruptions and white matter loss observed in human alcoholics. \u00a9 2012 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/glia.22327","type":"journal-article","created":{"date-parts":[[2012,3,19]],"date-time":"2012-03-19T14:50:09Z","timestamp":1332168609000},"page":"948-964","source":"Crossref","is-referenced-by-count":113,"title":["Toll\u2010like receptor 4 participates in the myelin disruptions associated with chronic alcohol 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