Skip to main content
Log in

Age-Associated Hypothalamic Glutamate Receptor Density: Effect of Dietary Protein

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

An age-associated (3–18 months) increase in hypothalamic glutamate receptor (HgluR) binding due to increase in receptor density (Bmax) was observed in rats maintained with normal (20%) protein diet. Short-term supplementation of low (5%) protein diet (LPD) and high (40%) protein diet (HPD) produced no significant change in the HgluR binding and Bmax in young as well as aged rats. Consumption of LPD for long-term period (LTP) increased the HgluR binding by increasing Bmax in young rats; whereas, intake of the same diet by the aged rats under similar condition reduced the HgluR binding by reducing Bmax. Unlike LPD, HPD intake by the young rats for LTP decreased the HgluR binding by decreasing affinity (1/KD) without altering Bmax. However, the aged rats when supplemented with HPD for LTP, the HgluR binding was increased due to increase in Bmax. Further, no age-induced increase in HgluR binding and Bmax was observed following short-term supplementation of LPD; whereas, long-term intake of LPD decreased the HgluR binding and Bmax in 18 months old rats compared to 3 months old rats under similar condition. On the other hand, HPD under LTP potentiated the age-induced increase in HgluR binding and Bmax. These results, thus, suggest that dietary protein affects the hypothalamic glutamatergic activity by modulating its receptor population depending on the age of the subject, quantity of dietary protein and its duration of supplementation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Shock, N. W. 1962. The physiology of aging. Sci. Am. 206:100–110.

    Google Scholar 

  2. Levin, P., Janda, J. K., Joseph, J. A., Ingram, D. K., and Roth G. S. 1981. Dietary restriction retards the age-associated loss of rat striatal dopaminergic receptors. Science 214:561–562.

    Google Scholar 

  3. Roth, G. S., Ingram, D. K., and Joseph, J. A. 1984. Delayed loss of striatal dopamine receptors during aging of dietarily restricted rats. Brain Res. 300:27–32.

    Google Scholar 

  4. Granger, R., Deadwylar, S., Davis, M., Moskovitz, B., Kessler, M., Rogers, G., and Lynch, G. 1996. Facilitation of glutamate receptors reverses an age-associated memory impairment in rats. Synapse 22:332–337.

    Google Scholar 

  5. Fonnum, F. 1984. Glutamate: A neurotransmitter in the mammalian brain. J. Neurochem. 42:1–11.

    Google Scholar 

  6. Watkins, J. C. and Evans, R. H. 1981. Excitatory aminoacid transmitters. Annu. Rev. Pharmacol. Toxicol. 21:165–204.

    Google Scholar 

  7. Oeriu, A. 1964. B. L. Strehler (Ed) In: Advances in Gerontological Research Vol. 1, Academic Press, New York, pp. 23–24.

    Google Scholar 

  8. Saransaari, P. and Oja, S. S. 1995. Age-related changes in the uptake and release of glutamate and aspartate in the mouse brain. Mech. Ageing Dev. 81:61–71.

    Google Scholar 

  9. Serra, M., Ghiani, C. A., Foddi, M. C., Motzo, C., and Biggio, G. 1994. NMDA receptor function is enhanced in the hippocampus of aged rats. Neurochem. Res. 19:483–487.

    Google Scholar 

  10. Ingram, D. K., Spangler, E. L., Iijima, S., Ikari, H., Kuo, H., Greig, N. H., and London, E. D. 1994. Rodent models of memory dysfunction in Alzheimer's disease and normal aging: moving beyond the cholinergic hypothesis. Life Sci. 55:2037–2049.

    Google Scholar 

  11. Pagliusi, S. R., Gerrard, P., Abdallah, M., Talabot, D. and Catsicas, S. 1994. Age-related changes in expression of AMPAselective glutamate receptor subunits: is calcium-permeability altered in hippocampal neurons? Neuroscience 61:429–433.

    Google Scholar 

  12. Pokras, R. S. 1994. A possible role of glutamate in the aging process. Med. Hypotheses 42:253–256.

    Google Scholar 

  13. Holehan, A. M. and Merry, B. J. 1986. The experimental manipulation of aging by diet. Biol. Rev. 61:329–368.

    Google Scholar 

  14. Armeni, T., Tomasetti, M., Svegliati Baroni, S., Saccucci, F., Marra, M., Pieri, C., Littarru, G. P., Principato, G., and Battino, M. 1997. Dietary restriction affects antioxidant levels in rat liver mitochondria during aging. Mol. Aspects Med. 18(suppl):S247–250.

    Google Scholar 

  15. Aksenova, M. V., Aksenov, M. Y., Carney, J. M., and Butterfield, D. A. 1998. Protein oxidation and enzyme activity decline in old brown Norway rats are reduced by dietary restriction. Mech. Aging Dev. 100:157–168.

    Google Scholar 

  16. Masoro, E. J. 1985. Nutrition and aging-A current assessment. J. Nutr. 115:842–848.

    Google Scholar 

  17. Masoro, E. J. 1993. Dietary restriction and aging. J. Am. Geriatr. Soc. 41:994–999.

    Google Scholar 

  18. Magnusson, K. R. 1997. Influence of dietary restriction on ionotropic glutamate receptors during aging in C57BI mice. Mech. Ageing Dev. 95:187–202.

    Google Scholar 

  19. Magnusson, K. R. 1997. The effects of age and dietary restriction on metabotropic glutamate receptors in C57BI mice, J. Gerontol. A. Biol. Sci. Med. Sci. 52:B291–299.

    Google Scholar 

  20. Kambara, T., McFarlane, R. G., Abell, T. J., McAnulty, R. W., and Sykes, A. R. 1993. The effect of age and dietary protein on immunity and resistance in lambs vaccinated with Trichostrongylus colubriformis. Int. J. Parasitol. 23:471–476.

    Google Scholar 

  21. Sonaka, I., Futami, Y., Kobayashi, T., Umezawa, T., and Maki, T. 1993. Effects of dietary protein restriction on nitrogen balance and cardiovascular functions in aged rats. J. Gerontol. 48:B145–150.

    Google Scholar 

  22. Bandyopadhyay, B. C., and Poddar, M. K. 1997. Is hypothalamic GABA involved in immune function in relation to dietary protein during aging? Neurochem. Res. 22:1135–1144.

    Google Scholar 

  23. Bandyopadhyay, B. C., and Poddar, M. K. 1998. Hypothalamic GABAergic activity and T-cell proliferation in aged mammal: effect of dietary protein. Neurochem. Int. 32:191–196.

    Google Scholar 

  24. Poddar, M. K., and Dewey, W. L. 1980. Effect of cannabinoids on catecholamine uptake and release in hypothalamus and striatal synaptosomes. J. Pharmac. Exp. Ther. 214:63–67.

    Google Scholar 

  25. Zukin, S. R., Young, A. B., and Snyder, S. H. 1974. GABA receptor binding to receptor sites in rat central nervous system. Proc. Natn. Acad. Sci. USA. 71:4802–4807.

    Google Scholar 

  26. Foster, A. C. and Roberts, P. J. 1978. High affinity L-[3H]glutamate binding to postsynaptic receptor sites on rat cerebellar membranes. J. Neurochem. 31:1467–1477.

    Google Scholar 

  27. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with Folin-phenol reagent. J. Biol. Chem. 193:265–275.

    Google Scholar 

  28. Goff, D. C. and Wine, L. 1997. Glutamate in schizophrenia: clinical and research implication. Schizophr. Res. 27:157–168.

    Google Scholar 

  29. Telang, S., Fuller, G., Wiggins, R., and Enna, S. J. 1984. Early undernutrition and [3H]-γ-aminobutyric acid binding in rat brain. J. Neurochem. 43:640–645.

    Google Scholar 

  30. Brann, D. W. and Mahesh, V. B. 1994. Excitatory aminoacids: function and significance in reproduction and endocrine regulation. Front Neuroendocrinol. 15:3–49.

    Google Scholar 

  31. Roberts, P. J. 1974. Glutamate receptors in the rat central nervous system. Nature 252:399–401.

    Google Scholar 

  32. Michaelis, E. K., Michaelis, M. L., and Boyarsk, L. L. 1974. High-affinity glutamate binding to brain synaptic membranes. Biochim. Biophys. Acta. 367:338–348.

    Google Scholar 

  33. Baudry, M. and Lynch, G. 1981. Characterisation of two [3H] glutamate binding sites in rat hippocampal membranes. J. Neurochem. 36:811–820.

    Google Scholar 

  34. Michaelis, E. K., Michaelis, M. L., Chang, H. H., Grubbs, R. D., and Kuonen, D. R. 1981. Molecular characteristics of glutamate receptors in the mammalian brain. Mol. Cell. Biochem. 38:163–179.

    Google Scholar 

  35. Yoneda, Y., Ogita, K., Ohgaki, T., Uchida, S., and Meguri, H. 1989. N-methyl-D-aspartate-sensitive [3H]glutamate binding sites in brain synaptic membranes treated with Triton X-100. Biochimica et Biophysica Acta 1012:74–80.

    Google Scholar 

  36. Tamaru, M., Yoneda, Y., Ogita, K., Shimizu, J., and Nagata, Y. 1991. Age-related decreases of the N-methyl-D-aspartate receptor complex in the rat cerebral cortex and hippocampus. Brain Res. 542:83–90.

    Google Scholar 

  37. Michaelis, E. K., Michaelis, M. L., Stormann, T. M., Chittenden, W. L., and Grubbs, R. D. 1983. Purification and molecular characterization of the brain synaptic membrane glutamatebinding protein. J. Neurochem. 40:1742–1753.

    Google Scholar 

  38. Fagg, G. E., Mena, E. E., Monaghan, D. T., and Cotman, C. W. 1983. Freezing eliminates a specific population of L-glutamate receptors in synaptic membranes. Neurosci. Lett. 38:157–162.

    Google Scholar 

  39. Wardas, J., Pietraszek, M., Schulze, G., Ossowska, K., and Wolfarth, S. 1997. Age-related changes in glutamate receptors: an autoradiographic analysis. Pol. J. Pharmacol. 49:401–410.

    Google Scholar 

  40. Mitchell, J. J. and Anderson, K. J. 1998. Age-related changes in [3H]MK-801 binding in the Fischer 344 rat brain. Neurobiol. Aging 19:259–265.

    Google Scholar 

  41. Miyoshi, R., Kito, S., Doudou, N., and Nomoto, T. 1991. Effect of age on α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding sites in the rat brain studied by in vitro autoradiography. Neurochem. Res. 16:849–854.

    Google Scholar 

  42. Hollander, J. and Barrows, C. H. 1968. Enzymatic studies in senescent rodent brain. J. Geront. 23:174–179.

    Google Scholar 

  43. Young, V. R. 1990. Amino acids and proteins in relation to the nutrition of elderly people. Age Ageing 19:S10–24.

    Google Scholar 

  44. Beckman, K. B. and Ames, B. N. 1998. The free radical theory of aging matures. Physiol. Rev. 78:547–581.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chakrabarti, L., Bandyopadhyay, B.C. & Poddar, M.K. Age-Associated Hypothalamic Glutamate Receptor Density: Effect of Dietary Protein. Neurochem Res 26, 145–151 (2001). https://doi.org/10.1023/A:1011046812540

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011046812540

Navigation