The Indian Journal of Nutrition and Dietetics

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Effect of Thiamine Nutritional Deficiency on the Energy Metabolism and Neurotransmission in Mice Brain


Affiliations
1 Department of Bio Science and Bio Technology, Banasthali University, Banasthali, Distt-Tonk, Rajasthan, India
2 Biochemistry Discipline, School of Sciences, IGNOU, Maidan Garhi, New Delhi - 110 068, India
     

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Thiamine or vitamin B1 has an antioxidant property. It plays a vital role in energy metabolism as it is directly or indirectly involved in the metabolism of lipids, glucose, amino acids and neuro transmitters. Present study emphasizes the role of thiamine deficiency (TD) on the mitochondrial enzymes involved in energy metabolism and neurotransmission. The study was carried out on Mus musculus in three groups, namely control and thiamine-deficient group for 8 (TD 8, group II) and 10 (TD 10, group III) days. Activity of TCA cycle enzymes such as succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and fumarase were measured along with the activity of enzyme acetylcholine esterase (Ach E) involved in the release of neurotransmitter. These biochemical changes were further correlated with histopathological changes in TD. A significant decrease in the enzymatic activity of SDH was found in group II (p<.05) and group III (p<.001) in comparison to the control group. Similarly a significant reduction in the enzymatic activity of MDH (p<0.0001) in the TCA cycle was also found in group III (TD 10). Fumarase levels were also found to be low in both the treated groups in comparison to the control. ACh E activity was also found to be decreased in group II (p<.05) and group III (p<.001) in comparison to the control group. Histopathological analysis via transmission electron microscopy (TEM) showed neurodegenerative features in the brain of thiamine deficient mice. Diminished activity of mitochondrial enzymes and ACh E suggests impairment in energy metabolism and disturbances in the release of neurotransmitter during TD. Pathological changes were also in conformity with the fact that TD impedes metabolism and its prolong impairments would further diminish brain functions. The present results suggest nutritional corrections with thiamine might lead to the improvement from neurological disorders or neurodegenerative conditions.

Keywords

Thiamine Deficiency, Energy Metabolism, Neurotransmitter, Neurological Disorders.
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  • Makini Chisolm-Straker and David Cherkas. Altered and unstable: wet beriberi, a clinical review. J. Emerg. Med., 2013, 45, 341-44.

  • Kraut, J. and Reed, H.J. The crystal structure of thiamine hydrochloride (vitamin B1). Acta. Crystallogr., 1962, 15, 747-57.

  • Scheffler, I.E. Biogenesis of mitochondria and mitochondrial electron transfer and oxidative phosphorylation. In: Mitochondria, Edn., 2008, 2, 60-297.

  • Lyubarev, A.E. and Kurganov, B.I. Supramolecular organization of tricarboxylic acid cycle enzymes. Biosystems, 1989, 22, 91-102.

  • Zielke, H.R., Carol L. Zielke and Peter J. Baab. Direct measurement of oxidative metabolism in the living brain by microdialysis: a review. J. Neurochem., 2009, 109 (Suppl 1), 24-29.

  • Witte, K.K., Clark, A.L. and Cleland, J.G. Chronic heart failure and micronutrients. J. Am. Coll. Cardiol., 2001, 37, 1765-1774.

  • Aikawa, H., Watanabe, I.S., Furuse, T., Iwasaki, Y., Satoyoshi, E., Takahiko Sumi and Takashi Moroji. Low energy levels in thiamine-defi- cient encephalopathy. J. Neuropathol. Exp. Neurol., 1984, 43, 276-287.

  • Hazell, A.S., Rao, K.V., Danbolt, N.C., David V. Pow and Roger F. Butterworth. Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental Wernicke’s encephalopathy. J. Neurochem., 2001, 78, 560-568.

  • Beal, M.F. Mitochondria, free radicals and neurodegeneration. Curr. Opin. Neurobiol., 1996, 6, 661-666.

  • Sheu, K.F., Calingasan, N.Y., Lindsay, J.G. and Gary E. Gibson. Immunochemical characterization of the deficiency of the alphaketoglutarate dehydrogenase complex in thiamine-deficient rat brain. J. Neurochem., 1998, 70 (3), 1143-1150.

  • Gibson, G.E., Haroutunian, V., Zhang, H., Park, L.C., Shi, Q., Lesser, M., Mohs, R.C., Sheu, R.K.F. and Blass, J.P. Mitochondrial damage in Alzheimer’s disease varies with apolipoprotein E genotype. Ann. Neurol., 2000, 48 (3), 297-303.

  • Gibson, G.E., Kingsbury, A.E., Xu, H., Lindsay, J.G., Daniel, S., Foster, O.J.F., Lees, A.J. and Blass, J.P. Deficits in tricarboxylic acid cycle in brains from patients with Parkinson’s disease. Neurochem. Int., 2003, 43, 129-135.

  • Butterworth, R.F., Jillian J. Kril and Clive G. Harper. Thiamine-dependent enzyme changes in the brains of alcoholics: relationship to the Wernicke–Korsakoff syndrome. Alcohol Clin. Exp. Res., 1993, 17 (5), 1084-1088.

  • Das, A., Dikshit, M. and Nath, C. Profile of acetylcholinesterase in brain areas of male and female rats of adult and old age. Life Sci., 2001, 68, 1545-1555.

  • Veeger, C., DerVartanian, D.V. and Zeylemaker, W.P. Succinate dehydrogenase. In: Lowenstein, J.M. (Ed.). Methods in Enzymol., 1969, 13, 106-116.

  • Kitto, G.B. Intra and extra mitochondrial malate dehydrogenases from chicken and tuna heart. In: Lowenstein, J.M. (Ed.). Methods in Enzymol., 1969, 13, 106-116.

  • Hill, R.L. and Bradshaw, R.A. Fumarase. In: Lowenstein, J.M. (Ed.). Methods in Enzymol., 1969, 13, 91-92.

  • Ellman, G.L., Courtney, K.D., Andres, V.J. and Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 1961, 7, 788-95.

  • Lowry, O.H., Rosenberg, N.J., Lewis Farr, A. and Rose J. Randal. Protein measurement with the Folin-Phenol reagent. J. Biochem., 1951, 193, 265-275.

  • Greenwood, J., Love, E.R. and Pratt, O.E. Kinetics of thiamine transport across the bloodbrain barrier in the rat. J. Physiol., 1982, 327, 95-103.

  • Bubber, P., Zun-Ji, Ke and Gary E. Gibson. Tricarboxylic acid cycle enzymes following thiamine deficiency. Neurochem. Int., 2004, 45, 1021-1028.

  • Bogdan, A.S. Effect of small amounts of 2, 4-dichlorophenoxyacetic acid derivatives on thiamine and riboflavin metabolism in the animal body. Neurol., 1983, 2, 59-62.

  • Shaikh, A., Tamloorkar, H.L. and Rafia Yasmeen. Malate dehydrogenase activity post exposure recovery from lead intoxicated freshwater fish anabas testudineus. Int. J. Biomed. Adv. Res., 2012, 3(2), 118-121.

  • Bubber, P., Hartounian, V., Gary E. Gibson and Blass, J.P. Abnormalities in the tricarboxylic acid (tca) cycle in brain of schizophrenia patients abnormalities in the tricarboxylic acid (tca) cycle in brain of schizophrenia patients. Eur. Neuropsychopharmacol., 2011, 21(3), 254-260.

  • Hakim, A.M. Effect of thiamine deficiency and its reversal on cerebral blood flow in the rat. Observations on the phenomena of hyperperfusion, ‘‘no reflow,’’ and delayed hypoperfusion. J. Cereb. Blood Flow Metab., 1986, 6, 79-85.

  • Roger F. Butterworth. Neurotransmitter function in thiaminedeficiency encephalopathy. Neurochem. Int., 1982, 4, 449-464.

  • Martin, P.R., Singleton, C.K. and Hiller-Sturmho, Fel, S. The role of thiamine deficiency in alcoholic brain disease. Alcohol Res. Health. 2003, 27, 134-142.

  • Jhala, S.S. and Hazell, A.S. Modeling neurodegenerative disease pathophysiology in thiamine deficiency: consequences of impaired oxidative metabolism. Neurochem. Int., 2011, 58, 248-260.

  • Matsushima, K., MacManus, J.P. and Hakim, A.M. Apoptosis is restricted to the thalamus in thiamine deficient rats. Neuro. Report, 1997, 8, 867-870.

  • Abdou, E. and Hazell, A.S. Thiamine Deficiency: An Update of pathophysiologic mechanisms and future therapeutic considerations, Neurochem Res., 2015, 40, 353-361.

  • Langlais, P.J. and Mair, R.G. Protective effects of the glutamate antagonist MK-801 on pyrithiamine-induced lesions and amino acid changes in rat brain. J. Neurosci., 1990, 10 (5), 1664-1674.

  • Nulton-Persson, A.C. and Szweda, L.I. Modulation of mitochondrial function by hydrogen peroxide. J. Biol. Chem., 2001, 276 (26), 23357-23361.

  • Navarro, A., Sanchez, Del Pino, Gomez, C., Peralta, J.L. and Boveris, A. Behavioral dysfunction, brain oxidative stress and impaired mitochondrial electron transfer in aging mice. Am. J. Physiol. Regulatory Integrative Comp. Physiol., 2002, 282, 985-992.

  • Bist, R., Misra, S. and Bhatt, D.K. Inhibition of lindane-induced toxicity using alpha-lipoic acid and vitamin E in the brain of Mus musculus. Protoplasma, 2010, 243, 49-53.

  • McCandless, D.W. Energy metabolism in the lateral vestibular nucleus in pyrithiamin-induced thiamin deficiency. In: Sable HZ, Gubler CJ, (eds). Thiamin: Twenty Years of Progress. Ann NY Acad Sci., 1982, 378, 355-364.

  • Plaitakis, A., Hwang, E.C., Van Woert, M.H., Peter I.A. Szilagyi and Soll Berl. Effect of thiamin deficiency on brain neurotransmitter systems. In: Sable HZ, Gubler CJ, (eds). Thiamin: Twenty Years of Progress. Ann. NY Acad Sci., 1982, 378, 367-381.

  • Gibson, G., Barclay, L. and. Blass, J.P. The role of the cholinergic system in thiamin deficiency. In: Sable HZ, Gubler CJ, (eds). Thiamin: Twenty Years of Progress. Ann. NY Acad Sci., 1982, 378, 382-403.

  • Baker, K.G., Harding, A.J., Halliday, G.M., Jillian J. Kril and Clive G. Harper. Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke’s encephalopathy. Neurosci., 1999, 91, 429-438.

  • Ke, Z.J., DeGiorgio, L.A., Volpe, B.T. and Gary, E. Gibson. Reversal of thiamine deficiency-induced neuro degeneration. J. Neuropathol. Exp. Neurol., 2003, 62, 195-207.

  • Wang, X., Wang, B., Fan, Z., Shi, X., Zun-ji Ke and Luo, J. Thiamine deficiency sinduces endoplasmic reticulum stress in neurons. Neurosci., 2007, 144(3), 1045-1056.

  • Beal, M.F. Aging, energy, and oxidative stress in neurodegenerative diseases. Ann. Neurol., 1995, 38 (3), 357-366.


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  • Effect of Thiamine Nutritional Deficiency on the Energy Metabolism and Neurotransmission in Mice Brain

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Authors

Anisha Chauhan
Department of Bio Science and Bio Technology, Banasthali University, Banasthali, Distt-Tonk, Rajasthan, India
Nidhi Srivastva
Department of Bio Science and Bio Technology, Banasthali University, Banasthali, Distt-Tonk, Rajasthan, India
Parvesh Bubber
Biochemistry Discipline, School of Sciences, IGNOU, Maidan Garhi, New Delhi - 110 068, India

Abstract


Thiamine or vitamin B1 has an antioxidant property. It plays a vital role in energy metabolism as it is directly or indirectly involved in the metabolism of lipids, glucose, amino acids and neuro transmitters. Present study emphasizes the role of thiamine deficiency (TD) on the mitochondrial enzymes involved in energy metabolism and neurotransmission. The study was carried out on Mus musculus in three groups, namely control and thiamine-deficient group for 8 (TD 8, group II) and 10 (TD 10, group III) days. Activity of TCA cycle enzymes such as succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and fumarase were measured along with the activity of enzyme acetylcholine esterase (Ach E) involved in the release of neurotransmitter. These biochemical changes were further correlated with histopathological changes in TD. A significant decrease in the enzymatic activity of SDH was found in group II (p<.05) and group III (p<.001) in comparison to the control group. Similarly a significant reduction in the enzymatic activity of MDH (p<0.0001) in the TCA cycle was also found in group III (TD 10). Fumarase levels were also found to be low in both the treated groups in comparison to the control. ACh E activity was also found to be decreased in group II (p<.05) and group III (p<.001) in comparison to the control group. Histopathological analysis via transmission electron microscopy (TEM) showed neurodegenerative features in the brain of thiamine deficient mice. Diminished activity of mitochondrial enzymes and ACh E suggests impairment in energy metabolism and disturbances in the release of neurotransmitter during TD. Pathological changes were also in conformity with the fact that TD impedes metabolism and its prolong impairments would further diminish brain functions. The present results suggest nutritional corrections with thiamine might lead to the improvement from neurological disorders or neurodegenerative conditions.

Keywords


Thiamine Deficiency, Energy Metabolism, Neurotransmitter, Neurological Disorders.

References