A multinuclear NMR study of glucose metabolismin thiamine-deficient cerebellar granule cells: new mechanistic insights

Introduction. Wernicke’s encephalopathy (WE) is a serious neurological disorder which is characterized by ataxia, nystagmus, ophtalmoplegia, disturbances in consciousness and region-selecticve brain lesions [1]. In most cases, brain damage in WE is associated with chronic alcoholism as a result of a deficiency in thiamine which is essential in the metabolic turnover of carbohydrates. Thiamine-deficiency (TD) leads to region-selective neuronal death and irreversible structural damages in advanced stages, which is suggested to be the result of impaired pyruvate oxidation and focal lactate accumulation. Furthermore, it is known that hyperglycemic conditions aggravate developing secondary brain damage in TD in vivo. In the present study, multinuclear NMR spectroscopy combined with the administration of [UC]glucose was used to assess in more detail changes in carbon fluxes and cellular energy state of thiamine-deficient cultured rat cerebellar granule neurons previously shown to manifest reduced α-KGDH activities, lactate accumulation and cell death.