BRAIN PYRUVATE OXIDATION IN EXPERIMENTAL THIAMIN-DEFICIENCY ENCEPHALOPATHY

Pyrithiamine-induced thiamin deficiency has been used in rat as an exp erimental form of Wernicke-Korsakoff encephalopathy, a disease associa ted with chronic alcoholism. Although the main etiological factor is k nown to be the lack of thiamin, the biochemical mechanisms involved in the pathogenesis remain unclear. Thiamin-dependent enzymes were studi ed in brain mitochondria: alpha-ketoglutarate dehydrogenase activity e xhibited 40% reduction, whereas pyruvate dehydrogenase did not change significantly. Polarographic recordings of mitochondrial respiration r evealed a decreased State 3, when using pyruvate/malate, alpha-ketoglu tarate or glutamine as a substrate, but the respiration rates remained unchanged with glutamate or succinate. This fall in pyruvate oxidatio n may be due to the impairment of alpha-ketoglutarate dehydrogenase, w hich follows pyruvate dehydrogenase in the metabolic pathway. A time c ourse of lactate concentration showed dramatic increases in thalamus, mid brain, hypothalamus and colliculli, consistent with the anatomopat hological findings. No increases were found before the onset of neurol ogical symptoms.