Focal thalamic degeneration from ethanol and thiamine deficiency is associated with neuroimmune gene induction, microglial activation, and lack of monocarboxylic acid transporters.
Bottom Line: Wernicke's encephalopathy-Korsakoff syndrome (WE-KS) is common in alcoholics, caused by thiamine deficiency (TD; vitamin B1) and associated with lesions to the thalamus (THAL).Combined EtOH-TD treatment for 5 days (EtOH-TD5) showed activated microglia, proinflammatory gene induction and THAL neurodegeneration that was greater than that found with TD alone (TD5), whereas 10 days resulted in marked THAL degeneration and microglial-neuroimmune activation in both groups.The findings support the hypothesis that TD deficiency inhibits global glucose metabolism and that a reduced ability to process acetate for cellular energy results in THAL focal degeneration in alcoholics contributing to the high incidence of Wernicke-Korsakoff syndrome in alcoholism.
Affiliation: Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.Show MeSH
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Mentions: To investigate the response of astrocytes to TD, we compared THAL and ENT using astrocyte markers glial fibrillary acidic protein (GFAP) (Fig. 7), glutamine synthetase (GS) (Fig. 8), and the excitatory amino acid transporter (EAAT1) (Fig. 9). In general, ENT astrocyte marker protein expression, for example, GFAP+IR, GS+IR, and EAAT1 + IR appears more robust than that found in THAL. EtOH-TD10 induced a loss of THAL astrocytes markers, consistent with TD-induced focal THAL degeneration involving toxicity to both neurons and astrocytes. Interestingly, astrocyte GFAP shows darker staining in TD10, in both THAL and ENT, but not in EtOH-TD10. In THAL, EtOH-TD10 has a few dark stained cells but a general loss, whereas in ENT, EtOH-TD10 shows GAFP + IR cell morphology more like controls than TD10 (Fig. 7). Quantification of GFAP + IR cells/mm2 morphological activation finds 59 ± 6% activated in TD, 17 ± 2% activated in EtOH + TD (p < 0.01 vs. TD alone; controls 2 ± 0.4; p < 0.01 vs. TD and EtOH + TD) consistent with EtOH reducing the TD astrocyte insult in ENT that contrasts with EtOH increasing microglial activation in THAL.
Affiliation: Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.