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Activities of thiamine-dependent enzymes in two experimental models of thiamine-deficiency encephalopathy:

1. The pyruvate dehydrogenase complex

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Abstract

Chronic thiamine deprivation in the rat leads to selective neuropathological damage in brainstem structures whereas treatment with the central thiamine antagonist, pyrithiamine, results in more widespread damage. In order to further elucidate the neurochemical mechanisms responsible for this selective damage, the thiamine-dependent enzyme complex pyruvate dehydrogenase (PDHC) was measured in 10 brain structures in the rat during progression of thiamine deficiency produced by chronic deprivation or by pyrithiamine treatment. Feeding of a thiamine-deficient diet to adult rats resulted in 5–7 weeks in ataxia and loss of righting reflex accompanied by decreased blood transketolase activities. PDHC activities were selectively decreased by 15–30% in midbrain and pons (lateral vestibular nucleus). Thiamine treatment of symptomatic rats led to reversal of neurological signs and to concomitant reductions of the cerebral PDHC abnormalities. Daily pyrithiamine treatment led within 3 weeks to loss of righting reflex and convulsions and to decreased blood transketolase of a comparable magnitude to that observed in chronic thiamine-deprived rats. No significant regional alterations of PDHC, however, were observed in pyrithiamine-treated rats.

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Authors and Affiliations

  1. Laboratory of Neurochemistry Clinical Research Centre, Hôpital Saint-Luc (University of Montreal), 1058 St. Denis St., H2X 3J4, Montreal, Qué., Canada

    Roger F. Butterworth, Jean-François Giguere & Anne-Marie Besnard

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  1. Roger F. Butterworth
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  2. Jean-François Giguere
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  3. Anne-Marie Besnard
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Butterworth, R.F., Giguere, JF. & Besnard, AM. Activities of thiamine-dependent enzymes in two experimental models of thiamine-deficiency encephalopathy:. Neurochem Res 10, 1417–1428 (1985). https://doi.org/10.1007/BF00964982

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