Metabolic Brain Disease

, Volume 6, Issue 3, pp 125–132 | Cite as

Pyrithiamine-induced thiamine deficiency results in decreased Ca2+-dependent release of glutamate from rat hippocampal slices

  • Oanh Lê
  • Maryse Héroux
  • Roger F. Butterworth
Original Contributions


Alterations of excitatory amino acids in brain may be of pathophysiological significance in thiamine-deficiency encephalopathy. The present study was undertaken to evaluate the effects of thiamine deficiency induced by the central thiamine antagonist, pyrithiamine, on the glutamate content of glutamatergic nerve terminals. Electrically-stimulated, Ca2+-dependent release of glutamate from hippocampal slices obtained from symptomatic pyrithiamine-treated rats was significantly decreased compared to pair-fed controls. Possible explanations for the decreased “neurotransmitter pool” of glutamate in thiamine-deficient rat brain include decreased synthesis of glutamate as a result of decreased activities of the thiamine-dependent enzyme α-ketoglutarate dehydrogenase or increased release of glutamateper se. There is evidence to suggest that the latter mechanism with ensuing excitotoxic neuronal damage could be involved in the pathogenesis of selective neuronal death in thiamine deficiency. Similar mechanisms could be implicated in Wemicke's encephalopathy in humans.

Key words

thiamine deficiency pyrithiamine glutamate release glutamate hippocampal slice Wemicke's encephalopathy Wemicke-Korsakoff syndrome 


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Copyright information

© Plenum Publishing Corporation 1991

Authors and Affiliations

  • Oanh Lê
    • 1
  • Maryse Héroux
    • 1
  • Roger F. Butterworth
    • 1
  1. 1.Laboratory of Neurochemistry, André-Viallet Clinical Research Center, Hopital Saint-LucUniversity of MontrealMontrealCanada

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