BACKGROUND: 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). Although TD alone can cause WE, the high 
incidence in alcoholism suggests that TD and ethanol (EtOH) interact.
METHODS: Mice in control, TD, or EtOH groups alone or combined were studied 
after 5 or 10 days of treatment. THAL and entorhinal cortex (ENT) histochemistry 
and mRNA were assessed.
RESULTS: 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. In 
contrast, 10 days of TD did not cause ENT degeneration. Interestingly, in ENT, 
TD10 activated microglia and astrocytes more than EtOH-TD10. In THAL, multiple 
astrocytic markers were lost consistent with glial cell loss. TD blocks glucose 
metabolism more than acetate. Acetate derived from hepatic EtOH metabolism is 
transported by monocarboxylic acid transporters (MCT) into both neurons and 
astrocytes that use acetyl-CoA synthetase (AcCoAS) to generate cellular energy 
from acetate. MCT and AcCoAS expression in THAL is lower than ENT prompting the 
hypothesis that focal THAL degeneration is related to insufficient MCT and 
AcCoAS in THAL. To test this hypothesis, we administered glycerin triacetate 
(GTA) to increase blood acetate and found it protected the THAL from TD-induced 
degeneration.
CONCLUSIONS: Our findings suggest that EtOH potentiates TD-induced THAL 
degeneration through neuroimmune gene induction. 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.