Indian Journal of Clinical Biochemistry

, Volume 18, Issue 1, pp 111–116 | Cite as

Effect of latent iron deficiency on GABA and glutamate neuroreceptors in rat brain

  • Rama Devi Mittal
  • Amita Pandey
  • Balraj Mittal
  • Kailash Nath Agarwal


Eight weeks of latent iron deficiency in weaned female rats of Sprague Dawley strain maintained on experimental low-iron diet (18–20 mg/kg) did not significantly change the gross body, weight and tissue weights of brain and liver. Packed cell volume (PCV) and hemoglobin concentration remained unaltered. However, non-heme iron content in liver and brain decreased significantly (p<0.001). The activities of glutamate dehydrogenase, glutamic acid decarboxylase, and GABA-transaminase (GABA-T) in brain decreased by 15%, 11.4% and 25.7% respectively. However, this decrease was not statistically significant. Binding of3H Muscimol at pH 7.5 and 1 mg protein/assay increased by 143% (p<0.001) in synaptic vesicular membranes from iron-deficient rats as compared to the controls.3H glutamate binding to the synaptic vesicles was also carried out under similar condition. However, the L-glutamate binding was reduced by 63% in the vesicular membranes of iron deficient animals. These studies indicate that iron plays important functional role in both excitatory and inhibitory neurotransmitter receptors.

Key words

Neurotransmitters Neurotransmitter receptors 3H glutamate [3H] Muscimol GABA/glutamate metabolism brain synaptic vesicles 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Baynes, R.D. and Bothwell,T.H. (1990) Iron deficiency. Annu. Rev. Nutr 10, 133–148PubMedCrossRefGoogle Scholar
  2. 2.
    American Medical Association Council of foods and Nutrition Committee on Iron deficiency (1968) Iron deficiency in the United States. J. Am. Med. Assoc. 203, 497Google Scholar
  3. 3.
    Shukla, A., Agarwal, K.N., Chansuria, J.P.N., and Taneja, V. (1989a) Effect of latent iron deficiency on 5-hydroxytryptamine metabolism in rat brain. J. Neurochem. 52, 730–735PubMedCrossRefGoogle Scholar
  4. 4.
    Shukla, A., Agarwal, K.N. and Shukla, G.S. (1989b) Effect of latent iron deficiency on metal levels of rat brain region. Biol. Trace. Ele. Res. 22, 141–152CrossRefGoogle Scholar
  5. 5.
    Pollit, E., Soemantri, A.G., Yonis F., and Scrimshaw, N.S. (1985) Cognitive effects of iron deficiency anemia. Lancet. 19, 158CrossRefGoogle Scholar
  6. 6.
    Pollit, E., and Kim, I (1988) Learning and achievement among iron deficient Brain Iron: Neuro-chemical and behavioral aspects (Youdim, M.B.H., ed.) pp 115–144, Taylor and Francis, New YorkGoogle Scholar
  7. 7.
    Agarwal, K.N. (1990) Effect of malnutrition and iron deficiency on mental function and study of possible mechanisms in animal model. Proc. Ind. Natl. Sci Acad B56(1) 43–50Google Scholar
  8. 8.
    Taneja, V; Mishra, K.P., and Agarwal, K.N. (1986) Effect of early iron deficiency in rat brain on the gamma-amino-butyric acid shunt in brain. J. Neurochem. 46, 1670–1674.PubMedCrossRefGoogle Scholar
  9. 9.
    Li, D. (1998) Effect of iron-deficiency on iron deficiency on iron distribution and gamma-amino-butyric acid (GABA)metabolism in young brain tissues. Hokkaido Igaku Zasshi, 73, 215–225.PubMedGoogle Scholar
  10. 10.
    Prasad C, Devi R, and Agarwal K.N. (1979) Effect of dietary protein on fetal brain protein and glutamic acid metabolism in rat. J Neurochem. 32, 1309–1314.PubMedCrossRefGoogle Scholar
  11. 11.
    Prasad, C., and Agarwal, K.N. (1980) Intrauterine malnutrition and brain: Effects on enzymes and free amino acids related to glutamate metabolism. J Neurochem. 34, 1270–1273.PubMedCrossRefGoogle Scholar
  12. 12.
    Lodge, D., and Johnson, K.N. (1990) Non-competitive excitatory amino acid receptor antagonists. Trends Pharmacol. Sci. 11, 81–86.PubMedCrossRefGoogle Scholar
  13. 13.
    Watkins, J.C., Krogsaardlarsen, P., and Honore, T. (1990) Structure activity relationships in development of receptor agonists and competitive antagonists. Trends Pharmacol Sci. 11, 25–33.PubMedCrossRefGoogle Scholar
  14. 14.
    Ito, M. (1989) Long-term depression. Annu. Rev. Neurosci. 12, 85–102.PubMedCrossRefGoogle Scholar
  15. 15.
    Rauschecker, J.P. (1991) Mechanism of visual plasticity-Hebb synapses, NMDA receptors and beyond. Physiol. Rev., 71, 210–214.Google Scholar
  16. 16.
    Bowery, N.G., Hill, D.R., and Hudson, A.L. (1983) Characteristics of GABA-B receptor binding sites on rat whole brain synaptic membrane. Br. J. Pharmacol. 78, 191–206.PubMedGoogle Scholar
  17. 17.
    Leinekugel, X., Khalilov, I., McLean, H., Callard, O., Gararsa, J.L., Ben-Ari, Y., and Khazipov, R. (1999) GABA is the fast-acting excitatory transmitter in neonatal brain. Adv. Neurol., 79, 189–201.PubMedGoogle Scholar
  18. 18.
    Newberry, N.R., and Nicoll, R.A. (1984) Direct hyper-polarizing action of baclofen on hippocampal pyramidal cells. Nature 308, 450–452.PubMedCrossRefGoogle Scholar
  19. 19.
    Nakanishi, S., Nakajima, Y., Masu, M., Ueda, Y., Nakahara, K., Watanabe, D., Yamaguchi, S., Kawabata, S., and Okada, M. (1998) Glutamate receptors: brain function and signal transduction. Brain Res. Rev. 2–3, 230–235.CrossRefGoogle Scholar
  20. 20.
    Ozawa, S., Kamiya, H., and Tsuzuki, K. (1998) Glutamate receptors in mammalian central nervous system. Prog. Neurobiol. 54, 581–618.PubMedCrossRefGoogle Scholar
  21. 21.
    Palmada, M., and Centelles, J.J. (1998) Excitatory amino-acid neurotransmission. Pathways for metabolism, storage and re-uptake of glutamate in brain. Front. Biosci 3, D701–718.Google Scholar
  22. 22.
    Hallgreen, B (1953) Hemoglobin formation and storage iron in protein deficiency. Acta Soc. Med. (Uppasala) 59, 79–200Google Scholar
  23. 23.
    Taneja, V., Mishra, K.P., and Agarwal, K.N. (1990) Effect of maternal iron deficiency on GABA shunt pathway of developing rat brain. Ind. J. Exp. Biol. 28, 466–469Google Scholar
  24. 24.
    Hell, J.W., Maycox, P.R., and John, R. (1990) Energy dependence and functional re-constitution of gamma-amino-butyric acid carrier from synaptic vesicles. J. Biol. Chem., 265, 2111–2117.PubMedGoogle Scholar
  25. 25.
    Seth, P.K., Agarwal, K.N., and Bondy, S.C. (1981) Biochemical changes in the brain consequently to dietary exposure to developing and mature rats to clorodecone. Toxicol. Appl. Pharmacol. 59, 262–267.PubMedCrossRefGoogle Scholar
  26. 26.
    Cross, A., Skan, W., and Slater, P. (1986) Binding sites for3H glutamate and3H aspartate in human cerebellum. J. Neurochem. 47, 1463–1468.PubMedCrossRefGoogle Scholar
  27. 27.
    Hall, H., and Thor, L. (1979) Evaluation of semiautomated filteration technique for receptor binding studies. Life. Sci. 24, 2293–2300.PubMedCrossRefGoogle Scholar
  28. 28.
    Siilmes, M.A., Refine, C., and Dallman, P.R. (1980) Manifestation of iron deficiency at various levels of dietary intake. Am. J. Clin. Nut. 3, 570–574.Google Scholar
  29. 29.
    Scheuer, K., Maras, A., Gattaz, W.F., Cairns, N., Forstl, H. and Muller, W.E. (1996) Cortical NMDA receptor properties and membrane fluidity are altered in Alzheimer's disease. Dementia 7, 210–214.PubMedCrossRefGoogle Scholar
  30. 30.
    Agarwal, K.N. (2001) Iron and the brain: neurotransmitter receptors and magnetic resonance spectroscopy. Br J Nutr. 2001 85 Suppl 2: S147–50.Google Scholar
  31. 31.
    Bordi, F. and Ugolini, A. (1999) Group I metabotropic glutamate receptors: implications for brain disease. Prog. Neurobiol. 59, 55–79.PubMedCrossRefGoogle Scholar
  32. 32.
    Albin, R.L., Young A.B. Pandey, J.B., Handelin, B., and Balfour, R., et al. (1990) Abnormalities of striatal projection neurons and N-methyl-D-aspartate receptors in presynaptic Huntington's disease. N. Engl. J. Med., 322, 1293–1298.PubMedCrossRefGoogle Scholar
  33. 33.
    Calabresi, P., Centonze, D., Pisani, A., and Bernardi, G. (1999) Metabotropic glutamate receptors and cell-type-specific vulnerability in the striatum: implications for ischemia and Huntington's disease. Expt. Neurol., 158, 97–108.CrossRefGoogle Scholar
  34. 34.
    Chalmers, D.T., Dewar, D., Graham, D.L., Brooks, D.N., and McCulloch, J. (1990) Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type. Proc. Natl. Acad. Sci. (USA) 87, 1352–1356.CrossRefGoogle Scholar
  35. 35.
    Sherwin, A.L. (1999) Neuro-active aminoacids in focally epileptic human brain: a review. Neurochem. Res., 24, 1387–1395.PubMedCrossRefGoogle Scholar
  36. 36.
    Kowel, N.W., Ferrante, R.J., and Martin, J.B. (1987) Pattern of cell loss in Huntington's disease. Trends Neurosci. 10, 24–29.CrossRefGoogle Scholar

Copyright information

© Association of Clinical Biochemists of India 2003

Authors and Affiliations

  • Rama Devi Mittal
    • 1
  • Amita Pandey
  • Balraj Mittal
    • 2
  • Kailash Nath Agarwal
  1. 1.Department of BiochemistrySanjay Gandhi Post Graduate Institute of Medical SciencesLucknowIndia
  2. 2.Department of GeneticsSanjay Gandhi Post Graduate Institute of Medical SciencesLucknowIndia

Personalised recommendations