Thiamine deficiency perturbed energy metabolism enzymes in brain mitochondrial fraction of Swiss mice

Abstract

BACKGROUND: Thiamine is an essential cofactor associated with several enzymes in energy metabolism and its deficiency may lead to neurological deficits. Current research evaluated the biochemical and molecular changes in TCA cycle enzymes using the mitochondrial fraction of the brain following thiamine deficiency (TD) in mice.

METHODS: The investigation was carried out on Swiss mice (6-8 week old) allocated into three groups. First group was control; second and third group were made thiamine deficient for 8 and 10 days.

RESULTS: Current study showed that alpha-ketoglutarate dehydrogenase (KGDHC) (thiamine-dependent enzyme) level found to be significantly reduced in experimental groups as compared to control group. In comparison to control group, a significant decrease in the succinate dehydrogenase (SDH) activity was calculated in group II and group III (p<0.0001) mice. Diminished enzymatic activity of fumarase and MDH enzyme in thiamine deficient groups exposed for 8 and 10 days was calculated as compared to control group. The expression analysis of different genes governing TCA cycle enzymes in different experimental groups showed that there was a negotiable change in the expression of fumarase and DLD (dihydrolipoyl dehydrogenase- E3 subunit of KGDHC) whereas a declined in the expression of SDH and two subunits of KGDHC i.e. OGDH (2-oxoglutarate dehydrogenase- E1 subunit of KGDHC) and DLST (dihydrolipoyllysine-residue succinyltransferase- E2 subunit of KGDHC) was observed as compared to control group.

CONCLUSIONS: Hence, current findings strongly entail that TD promotes alteration in energy metabolism in brain mitochondria which will decline the neuronal progression which may lead to neurodegenerative diseases such as Alzheimer’s diseases.

Keywords

thiamine / brain / TCA cycle enzymes / mitochondrial dysfunction

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Acknowledgments

Authors acknowledge Prof. Aditya Shastri, Vice- Chancellor, Banasthali University Rajasthan for providing the suitable facilities to carry out the present investigation in Department of Bioscience and Biotechnology. Authors are thankful to Indian Council of Medical Research (ICMR), New Delhi for financial support.

Compliance with ethics guidelines

Anupama Sharma received a research grant from ICMR, New Delhi. Anupama Sharma, Renu Bist and Surender Singh declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed in the current study.

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