NMDA Receptors, Aging and Alzheimer’s Disease

  • Kevin J. Anderson
  • Daniel T. Monaghan
  • James W. Geddes
Part of the Advances in Behavioral Biology book series (ABBI, volume 36)


Much research on the aging of the brain has been devoted in recent years to the possible alterations in specific neurotransmitter systems and the receptors which subserve neural transmission. This emphasis on transmitter systems is the result of the availability of new and specific ligands to probe receptor numbers and function as well as highly sensitive assays to directly measure transmitter content. The possibility that breakdowns in individual transmitter systems may correlate with specific clinical symptoms in aging-related disease has received much support, and indeed is well demonstrated in the dopaminergic dysfunction of Parkinson’s disease, and, to a lesser extent, the cholinergic deficits seen in Alzheimer’s disease (AD). However, it is not well understood how changes in transmitter systems during the course of “normal” aging affect brain function.


NMDA Receptor Entorhinal Cortex Excitatory Amino Acid Aged Brain Excitatory Amino Acid Receptor 
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  1. 1.
    Rothman, S.M. and J.W. Olney (1986) Glutamate and the pathology of hypoxic/ischemic brain damage. Ann. Neurol. 19: 105–111.Google Scholar
  2. 2.
    Rothman, S.M. and J.W. Olney (1987) Excitotoxicity and the NMDA receptor. TINS 10: 299–302.Google Scholar
  3. 3.
    Wieloch, T. (1986) Endogenous excitotoxins as possible mediators of ischemic and hypoglycemic brain damage. Prog. Brain Res. 63: 69–85.Google Scholar
  4. 4.
    Monaghan, D.T., Bridges, R.J. and Cotman, C.W. (1989) The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Ann. Rev. Pharmacol. Toxicol. 29: 365–402.Google Scholar
  5. 5.
    Cotman, C.W. and Iversen, L.L. (1987) Excitatory amino acids in the brain-focus on NMDA receptors. TINS 10: 263–264.Google Scholar
  6. 6.
    Ascher, P., and Nowak, L. (1987) Electrophysiological studies of NMDA receptors. TINS 10: 284–287.Google Scholar
  7. 7.
    Cline, H.T., Debski, E. and Constantine-Paton, M. (1987) NMDA receptor antagonist desegregates eye specific stripes. Proc. Natl. Acad. Sci. (USA) 84: 4342–4345.Google Scholar
  8. 8.
    Kleinschmidt, A., Bear, M.F. and Singer, W. (1987) Blockade of “NMDA” receptors disrupts experience-dependent plasticity of kitten striate cortex. Science 238: 355–358.CrossRefGoogle Scholar
  9. 9.
    Collingridge, G.L. and Bliss, T.V.P. (1987) NMDA receptors-their role in long-term potentiation. TINS 10: 288–293.Google Scholar
  10. 10.
    Chang, F. and Greenough, W.T. (1984) Transient and enduring morphological correlates of synaptic activity and efficacy change in the rat hippocampal slice. Brain Res. 309: 35–46.CrossRefGoogle Scholar
  11. 11.
    Lee, K., Schottler, F., Oliver, M., and Lynch, G. (1980) Brief bursts of high frequency stimulation produce two types of structural change in rat hippocampus. J. Neurophysiol. 44: 247–258.Google Scholar
  12. 12.
    Wieloch, T. (1985) Neurochemical correlates to selective neuronal vulnerability Prog. Brain Res. 63: 69–85.Google Scholar
  13. 13.
    Wieloch, T. (1985) Hypoglycemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonist. Science 230: 681–682CrossRefGoogle Scholar
  14. 14.
    Meldrum, B. (1985) Possible applications of antagonists of excitatory amino acid neurotransmitters. Clin. Sci. 68: 113–122.Google Scholar
  15. 15.
    Beneviste, H., Drejer, J., Schousboe, A., Diemer, N.H. (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J. Neurochem. 43: 1369–74.Google Scholar
  16. 16.
    Rothman, S.M., Olney, J.W. (1986) Glutamate and the pathology of hypoxic/ischemic brain damage. Annal. Neurol. 19: 105–110.Google Scholar
  17. 17.
    Sloviter, R.S. (1983) “Epileptic” brain damage in rats induced by sustained electrical stimulation of the perforant path. I. Acute electrophysiological and light microscopic studies. Brain Res. Bull. 10: 675–697.Google Scholar
  18. 18.
    Rothman, S.R., and Olney, J.W. (1987) Excitotoxicity and the NMDA receptor. TINS 10: 299–301.Google Scholar
  19. 19.
    Monaghan, D.T., Cotman, C.W. (1985) Distribution of NMDA-sensitive L[3H]-glutamate binding sites in rat brain as determined by quantitative autoradiography. J Neurosci 5: 2909–2919.Google Scholar
  20. 20.
    Geddes, J.W., Chang-Chui, H., Cooper, S.M., Lott, I.T., and Cotman, C.W. (1986) Density and distribution of NMDA receptors in the human hippocampus in Alzheimer’s disease Brain Res. 399: 156–161.Google Scholar
  21. 21.
    Greenamyre, J.T., Penney, J.B., D’Amato, C.J., and Young, A.B. (1987) Dementia of the Alzheimer type: changes in hippocampal L[3H]glutamate binding. J. Neurochem 48: 543–551.Google Scholar
  22. 22.
    Greenamyre, J.T., Penney, J.B., Young, A.B., D’Amato, C.J., Hicks, C.J., Shoulson, I. (1985) Alterations in L-glutamate binding in Alzheimer’s and Huntington’s disease. Science 227: 1496–1497.CrossRefGoogle Scholar
  23. 23.
    Monaghan, D.T., Geddes, J.W., Yao, D., Chung, C., and Cotman, C.W. (1987) [3H]TCP binding sites in Alzheimer’s disease. Neurosci Lett. 73: 197–200Google Scholar
  24. 24.
    Monaghan, D.T., McMillis, M.C., Chamberlin, A.R., and Cotman, C.W. (1983) Synthesis of [3H]-2-amino-4-phosphonobutyric acid and characterization of its binding to rat brain membranes: A selective ligand for the chloride/calcium dependent class of L-glutamate binding sites. Brain Res. 278: 137–144.CrossRefGoogle Scholar
  25. 25.
    Monaghan, D.T., Cotman, C.W. (1986) Identification and properties of NMDA receptors in rat brain synaptic plasma membranes. Proc. Natl. Acad. Sci. U.S.A. 83: 7532–36.Google Scholar
  26. 26.
    Bridges, R.J., M. Nieto-Sampedro, M. Kadri and C.W. Cotman (1987) A novel chloride-dependent L-[3H] glutamate binding site in astrocyte membranes, J. Neurochem. 48: 1709–1715.Google Scholar
  27. 27.
    Kessler, M., M. Baudry and G. Lynch (1987) Use of cystine to distinguish glutamate binding from glutamate sequestration. Neurosci. Left. 81: 221226.Google Scholar
  28. 28.
    Geddes, J.W., Monaghan, D.T., Bridges, R.J., and Cotman, C.W. (1987) Stability of L-glutamate receptors and decrease in a CaCI-dependent [3H]L-glutamate binding site in Alzheimer’s disease. Soc Neurosci Abstr 13: 436.Google Scholar
  29. 29.
    Palmer, A.M., A.W. Proctor, G.C. Stratmann and D.M. Bowen (1986) Excitatory amino acid-releasing and cholinergic neurones in Alzheimer’s disease. Neurosci. Lett. 66: 199–203.Google Scholar
  30. 30.
    Currie, D.N., and J.S. Kelly (1981) Glial versus neuronal uptake of glutamate J Exp. Biol. 95: 181–193.Google Scholar
  31. 31.
    Waniewski, R.A. and D.L. Martin. (1984) Characterization of L-Glutamic acid transport by glioma cells in culture: Evidence for sodium-independent, chloride-dependent high affinity influx. J Neurosci. 4: 2237–2246.Google Scholar
  32. 32.
    Morgan, D.G. (1987) The dopamine and serotonin systems during aging in human and rodent brain. A brief review. Prog. NeuroPsychopharmacol. Biol. Psychiat. 11: 153–157.Google Scholar
  33. 33.
    Giorgi, O., Calderini, G., Toffano, G. and Biggio, G. (1987) D-1 dopamine receptors labelled with 3H-SCH 23390: decrease in the striatum of aged rats. Neurobiol. Aging 8: 51–54.Google Scholar
  34. 34.
    Scarpace, P.J. and Abrass, I.B. (1988) Alpha-and beta-adrenergic receptor function in the brain during senescence. Neurobiol. Aging 9: 53–58.Google Scholar
  35. 35.
    Biegon, A., Duvdevani, R., Greenberger, V. and Segal, M. (1988) Aging and brain cholinergic muscarinic receptors: an autoradiographic study in the rat. J. Neurochem. 51: 1381–1385.Google Scholar
  36. 36.
    Gurwitz, D., Egozi, Y., Henis, Y.I., Kloog, Y., and Sokolovsky, M. (1987) Agonist and antagonist binding to rat brain muscarinic receptors: influence of aging. Neurobiol. Aging 8: 115–122.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Kevin J. Anderson
    • 1
  • Daniel T. Monaghan
    • 2
  • James W. Geddes
    • 2
  1. 1.Departments of Physiological Sciences and NeuroscienceUniversity of FloridaGainesvilleUSA
  2. 2.Department of SurgeryUniversity of CaliforniaIrvineUSA

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