Regional Reductions of Transketolase in Thiamine-Deficient Rat Brain |
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Authors: | Kwan-Fu Rex Sheu Noel Y Calingasan Gerald A Dienel Harriet Baker Eun-Hee Jung Kwang-Soo Kim †Francesco Paoletti Gary E Gibson |
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Institution: | Cornell University Medical College at Burke Medical Research Institute, White Plains, New York;and; Laboratory of Cerebral Metabolism, NIMH, Bethesda, Maryland, U.S.A.;and; Istituto di Patologia Generale, Universita di Firenze, Firenze, Italy |
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Abstract: | Abstract: Thiamine deficiency impairs oxidative metabolism and causes metabolic encephalopathy. An early reduction in transketolase (TK) activity may be an important pathogenic event. To assess the role of TK, we have delineated the regional/cellular distribution of TK protein and mRNA in adult rat brain in pyrithiamine-induced thiamine deficiency. TK activity declined in both vulnerable and spared regions. Immunoblots showed a parallel reduction of TK protein. With a few exceptions, immunocytochemistry indicated an overall decline of TK immunoreactivity and the decrease was not specific to vulnerable areas. In contrast to the pronounced, general decline of TK protein, in situ hybridization revealed a regional decrease of 0–25% of TK mRNA in thiamine deficiency. Northern blots indicated a similar level of TK mRNA in whole brain in thiamine deficiency. These results show that the decline of TK activity results from a proportional decrease of TK protein, and the deficiency may be due to an instability of TK protein or an inhibition of TK mRNA translation. The lack of correlation of the distribution, and the absence of specific alteration, of TK in affected regions suggest that the reduced TK may not be linked directly to selective vulnerability in thiamine deficiency. |
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Keywords: | Immunocytochemistry In situ hybridization Metabolic encephalopathy Thiamine deficiency Transketolase Thiamine pyrophosphate Wernicke-Korsakoff syndrome |
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