Focal Thalamic Degeneration from Ethanol and Thiamine Deficiency is Associated with Neuroimmune Gene Induction, Microglial Activation, and Lack of Monocarboxylic Acid Transporters.

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 (Et OH- 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 Et OH- 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 (AcCo AS) to generate cellular energy from acetate. MCT and AcCo AS expression in THAL is lower than ENT prompting the hypothesis that focal THAL degeneration is related to insufficient MCT and AcCo AS 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 Et OH 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. [ABSTRACT FROM AUTHOR]