A Multinuclear NMR Study of Glucose Metabolismin Thiamine-Deficient Cerebellar Granule Cells: New Mechanistic Insights

Abolghasem Mohammadi¹, Claudia Zwingmann¹

Wernicke's encephalopathy is a neurological disorder which is characterized by disturbances in consciousness and region-selective brain lesions. Brain damage is associated with a deficiency in thiamine, an essential vitamine in carbohydrate metabolism. Multinuclear NMR spectroscopy was used to assess carbon fluxes and cellular energy state of thiamine-deficient cultured rat cerebellar granule neurons. The data show that neuronal energy failure and death likely result from a primary impairment of neuronal a-KGDH causing impaired carbon flux from glucose/pyruvate through PDH, decreased catabolism of glutamine, and lactate accumulation. Under hyperglycemic conditions, however, alternative explanations to the lactic acidosis hypothesis have to be considered.