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NMDA receptor function is enhanced in the hippocampus of aged rats

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Abstract

The density and functional activity of theN-methyl-D-aspartate (NMDA)-sensitive glutamate receptor was examined in various brain areas of 3-, 18- and 24-month-old rats. The total numbers of binding sites for the NMDA receptor antagonists [3H]CGP 39653 and [3H]MK 801 binding sites were decreased in the hippocampus, cerebral cortex and striatum of 18- and 24-month-old rats, relative to 3-month-old animals. In the hippocampus of 18-month-old rats, the reduced number of NMDA receptors was associated with an increased sensitivity of [3H]MK 801 binding to the stimulatory action of glycine and glutamate. Thus, 10 μM glycine and 10 μM glutamate increased [3H]MK 801 binding in the hippocampus of 18-month-old rats by 75 and 160%, respectively; in 3-month-old animals, the same concentration of these amino acids increased binding by 37 and 95%, respectively. The sensitivity of [3H]MK 801 binding to glycine and glutamate was not increased in the cerebral cortex and striatum of aged rats. Moreover, an increased efficacy of glycine and glutamate in stimulating the binding of [3H]MK 801 in the hippocampus was no longer apparent in the 24-month-old rats. The increased sensitivity of [3H]MK 801 binding to glycine and glutamate in the hippocampus of 18-month-old rats may reflect an increase in NMDA receptor activity to compensate for the decrease in receptor number.

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References

  1. Bondareff W. 1979. Synaptic atrophy in the senescent hippocampus. Mech. Ageing Dev. 9:163–171.

    PubMed  Google Scholar 

  2. Bonhaus D. W., Perry W. B., and McNamara J. O. 1990. Decreased density, but not number, of N-methyl-D-aspartate, glycine and phencyclidine binding sites in hippocampus of senescent rats. Brain Res. 532:82–86.

    PubMed  Google Scholar 

  3. Brizee K. R., and Ordy J. M. 1979. Age pigments, cell loss and hippocampal function. Mech. Ageing Dev. 9:143–162.

    PubMed  Google Scholar 

  4. Collingridge G. L., and Bliss T. V. P. 1987. NMDA receptors—their role in long term potentiation. Trends Neurosci. 10:288–293.

    Google Scholar 

  5. Concas A., Pepitoni S. Atsoggiu T., Toffano G., and Biggio G. 1988. Aging reduces the GABA-dependent36Cl flux in rat brain membrane vesicles. Life Sci. 43:1761–1771.

    PubMed  Google Scholar 

  6. Danysz W., Wroblewski J. T., and Costa E. 1988. Learning impairment in rats by N-methyl-D-aspartate receptor antagonists. Neuropharmacology 27:653–657.

    PubMed  Google Scholar 

  7. Geinisman Y., Bondareff W., and Dodge J. T. 1978. Dendritic atrophy in the dentate gyrus of the senescent rat. Am. J. Anat. 153:537–543.

    PubMed  Google Scholar 

  8. Giorgi O., Calderini G., Toffano G., and Biggio G. 1987. D1-Dopamine receptors labelled with [3H]SCH 23390: decrease in the striatum of aged rats. Neurobiol. Aging 8:51–54.

    PubMed  Google Scholar 

  9. Huettner J. E., and Bean B. P. 1988. Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc. Natl. Acad. Sci. USA 85:1307–1311.

    PubMed  Google Scholar 

  10. Landfield P. W., McGaugh J. L., and Lynch G. 1978. Impaired synaptic potentiation processes in the hippocampus of aged, memory-deficient rats. Brain Res. 150:85–101.

    PubMed  Google Scholar 

  11. Lippa A. S., Critchett D. J., Ehlert F., Yamamura H. I., Enna S. J., and Bartus R. T. 1981. Age related alteration in neurotransmitter receptors: an electrophysiological and biochemical analysis. Neurobiol. Aging 2:3–8.

    PubMed  Google Scholar 

  12. Loo P., Braunwalder A., Lehmann J., and Williams M. 1986. Radioligand binding to central phencyclidine recognition sites is dependent on excitatory amino acid receptor agonists. Eur. J. Pharmacol. 123:467–468.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  14. Morris R. G. M., Anderson E., Lynch G. S., and Baudry M. 1986. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-d-aspartate receptor antagonist AP5. Nature 319:774–776.

    PubMed  Google Scholar 

  15. Munson P. J., and Rodbard D. 1980. Ligand: a versatile computerized approach for characterization of ligand binding systems. Anal. Biochem. 107:220–239.

    PubMed  Google Scholar 

  16. Peterson C., and Cotman C. W. 1989. Strain-dependent decrease in glutamate binding to the N-methyl-D-aspartic acid receptor during aging. Neurosci. Lett. 104:309–313.

    PubMed  Google Scholar 

  17. Piva F., Maggi R., Limonta P., Dondi D., and Martini L. 1987. Decrease of mu opioid receptors in the brain and in the hypothalamus of the aged male rat. Life Sci. 40:391–398.

    PubMed  Google Scholar 

  18. Reynolds I. J., Murphy S. N., and Miller R. J. 1987. [3H]-labeled MK-801 binding to the excitatory amino acid receptor complex from rat brain is enhanced by glycine. Proc. Natl. Acad. Sci. USA 84:7744–7748.

    PubMed  Google Scholar 

  19. Reynolds I. J., and Miller R. J. 1988. [3H]MK 801 binding to the NMDA receptor ionophore complex is regulated by divalent cations: evidence for multiple regulatory sites. Eur. J. Pharmacol. 151:103–112.

    PubMed  Google Scholar 

  20. Sills M. A., Fagg G. Pozza M., Angst C. Brundish D. E., Hurt S. D., Wilusz E. J., and Williams M. 1991. [3H]CGP 39653: a new N-methyl-D-aspartate antagonist radioligand with low nanomolar affinity in rat brain. Eur. J. Pharmacol. 192:19–24.

    PubMed  Google Scholar 

  21. Tamaru M., Yoneda Y., Ogita K., Shimiru 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.

    PubMed  Google Scholar 

  22. Waddington J. L., and Cross A. J. 1978. Denervation supersensitivity in the striatonigral GABA pathway. Nature 276:618–620.

    PubMed  Google Scholar 

  23. Williams K., Romano C., and Molinoff P. B. 1989. Effects of polyamines on the binding of [3H]MK-801 to the N-methyl-D-aspartate receptor: pharmacological evidence for the existence of a polyamine recognition site. Mol. Pharmacol. 36:575–581.

    PubMed  Google Scholar 

  24. Wong E. H. F., Kemp J. A., Priestley T., Knight A. R., Woodruff G. N., and Iversen L. L. 1986. The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc. Natl. Acad. Sci. USA 83:7104–7108.

    PubMed  Google Scholar 

  25. Wong E. H. F., Knight A. R., and Woodruff G. N. 1988. [3H]MK-801 labels a site on the N-methyl-D-aspartate receptor channel complex in rat brain membranes. J. Neurochem. 50:274–281.

    PubMed  Google Scholar 

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Serra, M., Ghiani, C.A., Foddi, M.C. et al. NMDA receptor function is enhanced in the hippocampus of aged rats. Neurochem Res 19, 483–487 (1994). https://doi.org/10.1007/BF00967328

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