Neurochemical Research

, Volume 20, Issue 7, pp 859–862 | Cite as

Glutamine synthetase (GS) expression is reduced in senile dementia of the Alzheimer type

  • Ghislaine Le Prince
  • Pia Delaere
  • Christiane Fages
  • Thierry Lefrançois
  • Monique Touret
  • Marcelle Salanon
  • Marcienne Tardy
Original Articles


Glutamine synthetase (GS), a metabolic marker of the mature astrocyte, was investigated in the temporal neocortex of postmortem brain samples of 8 cases, either not demented or affected by senile dementia of the Alzheimer type. A negative correlation between the GS protein level and the density of both classical βA4 deposits and senile plaques was evidenced. Such a correlation for GS underlies a dysfunction of the astroglial metabolism and particularly of the glutamate and ammonia neutralization. Since GS is sensitive to oxidative lesioning, the changes in GS level that were observed, occurring at the posttranslational stage, might reflect oxidative damage and have severe consequences on the pathological cascade of events.

Key Words

Blessed test score astrocyte classical senile plaque βA4 classical deposits 


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  1. 1.
    Khelil, M., Rolland, B., Fages, C., and Tardy, M., 1990. Glutamine synthetase modulation in astrocyte cultures of different mouse brain areas. Glia. 3:75–80.PubMedGoogle Scholar
  2. 2.
    Patel, A. J., Hunt, A., Tabourdin, C. S., 1983. Regional development of glutamine synthetase activity in the rat brain and its association with the differentiation of astrocytes. Dev. Brain Res. 8:31–37.Google Scholar
  3. 3.
    Le Prince, G., Delaere, P., Fages, C., Duyckaerts, C., Hauw, J. J., and Tardy, M., 1993. Alterations of glial fibrillary acidic protein m RNA level in the aging brain and in senile dementia of the Alzheimer type, Neurosci. Lett. 151:71–73.PubMedGoogle Scholar
  4. 4.
    Blessed, G., Tomlinson, B. E., and Roth, M., 1968. The association between quantitative measures of dementia and of senile changes in the cerebral grey matter of elderly subjects, Br. J. Psychiat. 114–797.Google Scholar
  5. 5.
    Delaere, P., Duyckaerts, C., He, Y., Piette, F., and Hauw, J-J, 1991. Subtypes and differential laminar distributions of βA4 deposits in Alzheimer's disease: relationship with the intellectual status of 26 cases, Acta Neuropathol. 81:328–335.PubMedGoogle Scholar
  6. 6.
    Charriere-Bertrand, C., Le Prince, G., Fages, C., Tardy, M., and Nunez, J., 1989. Expression of Tubulin, GFAP and of their encoding mRNAs during the proliferation and differentiation of cultured astrocytes, Neurochemistry Int. 15:215–222.Google Scholar
  7. 7.
    Sallanon, M., Touret, M., Didier-Bazes, M., Belin, M. F., Tardy, M., Jouvet, M., 1992. Paradoxical sleep deprivation increases glutamine synthetase in rat brain. C. R. Acad. Sci. Paris. 315:109–114.PubMedGoogle Scholar
  8. 8.
    Fages, C., Rolland, B., Dias Costa, M. F., Khelil, M., Dupré, G., Campagnoni, A. T., and Tardy, M., 1988. Messenger RNA coding for glutamine synthetase in cerebral hemispheres and astroglial cultures from mouse brain: a developmental study, Neurochem. Int. 12:307–313.Google Scholar
  9. 9.
    Mearow, K. M., Mill, J. F., Freese, E., 1990. Neuron-glia interactions involved in the regulation of glutamine synthetase, Glia 3:385–392.PubMedGoogle Scholar
  10. 10.
    Condorelli, D. F., Avola, R., Belluardo, N., Insirello, L., Nicoletti, V. G., Carpano, P., Bindoni, M., Giufrida Stella, A. M., 1988. Astroglial response to injury of hippocampal neurons. Senile dementia. II international Symposium. Agnoli A., Cahn J., Lassen N., Mayeux R., eds J Libbey Eurotext, Paris. 27–39.Google Scholar
  11. 11.
    Fages, C., Le Prince, G., Didier-Bazes, M., Rolland, B., Hardin, H., and Tardy, M., 1994. Long term astroglial reaction to serotoninergic fiber degeneration, Brain Res. 639:161–166.PubMedGoogle Scholar
  12. 12.
    Condorelli, D. F., Dell'Albani, P., Kaczmarek, L., Messina, L., Spampinato, G., Avola, R., Messina, A., Giufrida Stella, A. M., 1990. Glial fibrillary acidic protein messenger RNA and glutamine synthetase activity after nervous system injury, J. Neurosci. Res. 26: 251–257.PubMedGoogle Scholar
  13. 13.
    Jacque, C., Rolland, B., Caldani, M., Fages, C., and Tardy, M., 1986. Absence of correlations between glutamine synthetase activity and dysmyelination-associated modifications of astroglia in the brain of murine mutants. Neurochem. Res. 11:527–533.PubMedGoogle Scholar
  14. 14.
    Norenberg, M. D., 1994. Astrocyte responses to CNS injury, J. Neuropathol. Exp. Neurol. 53:213–220.PubMedGoogle Scholar
  15. 15.
    Oliver, C. N., Starke-Reed, P. E., Stadtman, E. R., Liu, G. J., Carney, J. M., and Floyd, R. A., 1990. Oxydative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc. Natl. Acad. Sci. USA. 87:5144–5147.PubMedGoogle Scholar
  16. 16.
    Carney, J. M., and Floyd, R. A., 1991. Protection against oxidative damage to CNS by a-phenyl-tert-butyl nitrone (PBN) and other spintrapping agents: a novel series of nonlipid free radical scavengers, J. Mol. Neurosci. 3:47–57.PubMedGoogle Scholar
  17. 17.
    Lazarini, F., Boussin, F., Desly, J. P., Tardy, M., and Dormont D., 1994. Astrocyte gene expression in experimental mouse scrapie, J. Comp. Path. 111:87–98.PubMedGoogle Scholar
  18. 18.
    Lefrançois, T., Fages, C., Brugère-Picoux, J., and Tardy, M., 1994. Astroglial reactivity in natural scrapie of sheep. Microb. Pathogenesis. 17:283–289.Google Scholar
  19. 19.
    Liaw, S. H., Villafranca, J. J., and Eisenberg, D., 1993. A model for Oxydative Modification of Glutamine synthetase based on cristal structures of mutant H269N and the Oxidized enzyme, Biochemistry. 32:7999–8003.PubMedGoogle Scholar
  20. 20.
    Hensley, K., Carney, J. M., Mattson, M. P., Aksenova, M., Harris, M., Wu, J. F., Floyd, R. A., and Butterfield, D. A., 1994. A model for β amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease, Proc. Natl. Acad. Sci. USA. 91:3270–3274.PubMedGoogle Scholar
  21. 21.
    Mattson, M. P., and Scheff, S. W., 1994. Endogenous neuroprotection factors and traumatic brain injury: mechanisms of action and implications for therapy, J. Neurotrauma 11:3–33.PubMedGoogle Scholar
  22. 22.
    Carl, G. F., Blackwell, L. K., Barnett, F. C., Thompson, L. A., Rissinger, C. G., Olin, K. L., Critchfield, J. W., Keen, C. L., and Gallagher, B. B., 1993. Manganese and epilepsy: Brain glutamine synthetase and liver arginase activities in genetically epilepsy prone and chronically seizured rats, Epilepsia 34:441–446.PubMedGoogle Scholar
  23. 23.
    Volterra, A., Trotti, D., Cassutti, P., Tromba, C., Salvaggio, A., Melcangi, R. G., Racagni, G., 1992. High sensitivity of glutamate uptake to extracellular free arachodonic acid levels in rat cortical synaptosomes and astrocytes, J. Neurochem. 59:600–606.PubMedGoogle Scholar
  24. 24.
    Noble, L. J., Hall, J. J., Chen, S., and Chan, P. H., 1992. Morphologic changes in cultured astrocytes after exposure to glutamate, J. of Neurotrauma 9:255–267.Google Scholar
  25. 25.
    Cornell-Bell, A. H., Finkbeiner, S. M., Cooper, M. S., and Smith, S. J., 1990. Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling, Science 247:470–473.PubMedGoogle Scholar
  26. 26.
    Staub, F., Peters, J., Kempski, O., Schneider, G. H., Schürer, L., and Baethmann, A., 1993. Swelling of glial cells in lactacidosis and by glutamate: significance of Cl transport, Brain Res. 610:69–74.PubMedGoogle Scholar
  27. 27.
    Benjamin, A. M., 1983. Ammonia in metabolic reactions between neurons and Hertz L., Kwamme E., Mc Geer E. G., Schousboe A. (eds.) Glutamin, Glutamate and GABA in the Central Nervous System. NY Alan R. Liss Inc. 399–414.Google Scholar

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Ghislaine Le Prince
    • 1
  • Pia Delaere
    • 2
  • Christiane Fages
    • 1
  • Thierry Lefrançois
    • 1
  • Monique Touret
    • 3
  • Marcelle Salanon
    • 3
  • Marcienne Tardy
    • 1
  1. 1.Inserm U 421, Faculté de MédecineHôpital Henri MondorCreteil cedexFrance
  2. 2.Laboratoire de Neuropathologie Raymond Escourolle, INSERM U 360, Association Claude BernardHôpital de la SalpêtrièreParis cedex 13France
  3. 3.Department de Médecine ExpérimentaleUniversité Claude BernardLyon cedex 08France

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