Vitamin E exists in eight different forms, four tocopherols and four tocotrienols. It forms an important component of our antioxidant system. The structure of Vitamin E makes it unique and indispensable in protecting cell membranes. α-tocopherol, one of the forms of Vitamin E, is also known to regulate signal transduction pathways by mechanisms that are independent of its antioxidant properties. Vitamin E compounds reduce the production of inflammatory compounds such as prostaglandins. Swollen, dystrophic axons are considered as the hallmark of Vitamin E deficiency in the brains of rats, monkeys, and humans. The present work aimed to study the Vitamin E- (α-tochopherol acetate-) induced alterations of enzymes involved in metabolism of Glutamate and GABA during developmental neurogenesis of cerebrum. Therefore, cytosolic and crude mitochondrial enzyme activities of glutamine synthetase, aspartate transaminase, alanine transaminase, GABA transaminase, succinic Semialdehyde dehydrogenase, glutamic dehydrogenase, and α-Ketoglutarate dehydrogenase were analysed. Vitamin E induced significant changes in these enzymes thus altering the normal levels of glutamate and GABA during developmental neurogenesis. Such changes are surely to disturb the expression and/or intensity of neurotransmitter signaling during critical periods of brain development. 1. Introduction Vitamin E activity was first identified in the year 1936 from a dietary fertility factor in rats. Tocopherols (or TCPs) constitute a class of chemical compounds which possess Vitamin E activity. They are series of organic compounds consisting of various methylated phenols. Vitamin E exists in eight different forms, four tocopherols and four tocotrienols. Each form has a chromanol ring, with a hydroxyl group that can donate a hydrogen atom to reduce free radicals and a hydrophobic side chain which allows for penetration into biological membranes. Both the tocopherols and tocotrienols occur in alpha, beta, gamma, and delta forms, designated by the number of methyl groups on the chromanol ring. The alpha is most highly methylated having maximum of three methyl groups on the chromanol ring in comparison with beta, gamma, and delta forms having two, one, and no methyl groups on the chromanol ring, respectively. Synthetic Vitamin E derived from petroleum products is manufactured as all-racemic alpha tocopheryl acetate with a mixture of eight stereoisomers. In this mixture, one alpha-tocopherol molecule in eight molecules is in the form of RRR-alpha-tocopherol. The eight stereoisomers of alpha-tocopherol
References
[1]
M. G. Traber, “Vitamin E,” in Present Knowledge in Nutrition, B. A. Bowman and R. M. Russel, Eds., vol. 1, pp. 211–219, International Life Sciences Institute, Washington, DC, USA, 2006.
[2]
S. Roy, B. H. Lado, S. Khanna, and C. K. Sen, “Vitamin E sensitive genes in the developing rat fetal brain: a high-density oligonucleotide microarray analysis,” FEBS Letters, vol. 530, no. 1–3, pp. 17–23, 2002.
[3]
D. P. R. Muller and M. A. Goss-Sampson, “Role of vitamin E in neural tissue,” Annals of the New York Academy of Sciences, vol. 570, pp. 146–155, 1989.
[4]
D. P. R. Muller and M. A. Goss-Sampson, “Neurochemical, neurophysiological, and neuropathological studies in vitamin E deficiency,” Critical Reviews in Neurobiology, vol. 5, no. 3, pp. 239–263, 1990.
[5]
K. C. Hayes, “Retinal degeneration in monkeys induced by deficiencies of vitamin E or A,” Investigative Ophthalmology, vol. 13, no. 7, pp. 499–510, 1974.
[6]
W. G. Robison Jr., T. Kuwabara, and J. G. Bieri, “Deficiencies of vitamins E and A in the rat. Retinal damage and lipofuscin accumulation,” Investigative Ophthalmology and Visual Science, vol. 19, no. 9, pp. 1030–1037, 1980.
[7]
A. Pentschew and K. Schwarz, “Systemic axonal dystrophy in vitamin E deficient adult rats—with implication in human neuropathology,” Acta Neuropathologica, vol. 1, no. 4, pp. 313–334, 1962.
[8]
J. S. Nelson, C. D. Fitch, and V. W. Fischer, “Progressive neuropathologic lesions in vitamin E-deficient rhesus monkeys,” Journal of Neuropathology and Experimental Neurology, vol. 40, no. 2, pp. 166–186, 1981.
[9]
M. L. Thakur and U. S. Srivastava, “Vitamin-E metabolism and its application,” Nutrition Research, vol. 16, no. 10, pp. 1767–1809, 1996.
[10]
K. Beeker, C. Smith, and S. Pennington, “Effect of cocaine, ethanol or nicotine on ornithine decarboxylase activity in early chick embryo brain,” Developmental Brain Research, vol. 69, no. 1, pp. 51–57, 1992.
[11]
A. Meluzzi, F. Sirri, G. Manfreda, N. Tallarico, and A. Franchini, “Effects of dietary vitamin E on the quality of table eggs enriched with n-3 long-chain fatty acids,” Poultry Science, vol. 79, no. 4, pp. 539–545, 2000.
[12]
J. Galobart, A. C. Barroeta, M. D. Baucells, L. Cortinas, and F. Guardiola, “α-tocopherol transfer efficiency and lipid oxidation in fresh and spray-dried eggs enriched with ω3-polyunsaturated fatty acids,” Poultry Science, vol. 80, no. 10, pp. 1496–1505, 2001.
[13]
H. A. Shahriar, K. N. Adl, Y. E. Nezhad, R. S. Nobar, and A. Ahmadzadeh, “Effect of dietary fat type and different levels of vitamin E on broiler breeder performance and vitamin E levels of egg,” Asian Journal of Animal and Veterinary Advances, vol. 3, no. 3, pp. 147–154, 2008.
[14]
K. Kuriyama, B. Sisken, J. Ito, D. G. Simonsen, B. Haber, and E. Roberts, “The γ-aminobutyric acid system in the developing chick embryo cerebellum,” Brain Research, vol. 11, no. 2, pp. 412–430, 1968.
[15]
W. B. Rowe, “Glutamine synthetase from muscle,” in Methods in Enzymology, A. Meister, Ed., vol. 113, pp. 119–212, Academic Press, New York, NY, USA, 1985.
[16]
F. Sherif, L. Eriksson, and L. Oreland, “Gamma-aminobutyrate aminotransferase activity in brains of schizophrenic patients,” Journal of Neural Transmission, vol. 90, no. 3, pp. 231–240, 1992.
[17]
M. T. Ryzlak and R. Pietruszko, “Human brain “high Km” aldehyde dehydrogenase: purification, characterization, and identification as NAD+-dependent succinic semialdehyde dehydrogenase,” Archives of Biochemistry and Biophysics, vol. 266, no. 2, pp. 386–396, 1988.
[18]
H. F. Fisher, “L-Glutamate dehydrogenase from bovine liver, in Glutamate, Glutamine, Glutathione, and Related Compounds,” in Methods in Enzymology, A. Meister, Ed., vol. 113, pp. 16–27, Academic Press, New York, NY, USA, 1985.
[19]
O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall, “Protein measurement with the Folin phenol reagent,” The Journal of biological chemistry, vol. 193, no. 1, pp. 265–275, 1951.
[20]
K. Hilscherova, A. L. Blankenship, M. Nie et al., “Oxidative stress in liver and brain of the hatchling chicken (Gallus domesticus) following in ovo injection with TCDD,” Comparative Biochemistry and Physiology C, vol. 136, no. 1, pp. 29–45, 2003.
[21]
D. Chatterjee and P. K. Sarkar, “Ontogeny of glutamine synthetase in rat brain,” International Journal of Developmental Neuroscience, vol. 2, no. 1, pp. 55–60, 1984.
[22]
M. Caldani, B. Rolland, C. Fages, and M. Tardy, “Glutamine synthetase activity during mouse brain development,” Experientia, vol. 38, no. 10, pp. 1199–1202, 1982.
[23]
K. M. Mearow, J. F. Mill, and L. Vitkovic, “The ontogeny and localization of glutamine synthetase gene expression in rat brain,” Molecular Brain Research, vol. 6, no. 4, pp. 223–232, 1989.
[24]
I. Suárez, G. Bodega, and B. Fernández, “Glutamine synthetase in brain: effect of ammonia,” Neurochemistry International, vol. 41, no. 2-3, pp. 123–142, 2002.
[25]
F. Rothe, W. Schmidt, and G. Wolf, “Postnatal changes in the activity of glutamate dehydrogenase and aspartate aminotransferase in the rat nervous system with special reference to the glutamate transmitter metabolism,” Brain Research, vol. 313, no. 1, pp. 67–74, 1983.
[26]
R. Luján, R. Shigemoto, and G. López-Bendito, “Glutamate and GABA receptor signalling in the developing brain,” Neuroscience, vol. 130, no. 3, pp. 567–580, 2005.
[27]
C. J. Carter, “Increased alanine aminotransferase activity in the Huntington's disease putamen,” Journal of the Neurological Sciences, vol. 66, no. 1, pp. 27–32, 1984.
[28]
M. Erecinska, S. Cherian, and I. A. Silver, “Energy metabolism in mammalian brain during development,” Progress in Neurobiology, vol. 73, no. 6, pp. 397–445, 2004.
[29]
M. Jelitai and E. Madarasz, “The role of GABA in the early neuronal development,” International Review of Neurobiology, vol. 71, pp. 27–62, 2005.
[30]
M. Maitre, “The γ-hydroxybutyrate signalling system in brain: organization and functional implications,” Progress in Neurobiology, vol. 51, no. 3, pp. 337–361, 1997.
[31]
G. S. Burbaeva, M. S. Turishcheva, E. A. Vorobyeva, O. K. Savushkina, E. B. B. Tereshkina, and I. S. Boksha, “Diversity of glutamate dehydrogenase in human brain,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 26, no. 3, pp. 427–435, 2002.
[32]
E. S. Schmidt and F. W. Schmidt, “Glutamate dehydrogenase: biochemical and clinical aspects of an interesting enzyme,” Clinica Chimica Acta, vol. 173, no. 1, pp. 43–55, 1988.
[33]
G. Wolf and G. Schunzel, “Glutamate dehydrogenase in aminoacidergic structures of the postnatally developing rat cerebellum,” Neuroscience Letters, vol. 78, no. 1, pp. 7–11, 1987.
[34]
F. Rothe, M. Brosz, and J. Storm-Mathisen, “Quantitative ultrastructural localization of glutamate dehydrogenase in the rat cerebellar cortex,” Neuroscience, vol. 62, no. 4, pp. 1133–1146, 1994.
[35]
G. A. Zündorf, S. Kahlert, V. I. Bunik, and G. Reiser, “α-Ketoglutarate dehydrogenase contributes to production of reactive oxygen species in glutamate-stimulated hippocampal neurons in situ,” Neuroscience, vol. 158, no. 2, pp. 610–616, 2009.
[36]
G. E. Gibson, V. Haroutunian, H. Zhang et al., “Mitochondrial damage in Alzheimer’s disease varies with apolipoprotein E genotype,” Annals of Neurology, vol. 48, no. 3, pp. 297–303, 2000.
