SpringerLink
Log in

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

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

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.

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

Access this article

Log in via an institution

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  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.

    PubMed  Google Scholar 

  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. 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.

    PubMed  Google Scholar 

  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.

  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.

    PubMed  Google Scholar 

  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. 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.

    PubMed  Google Scholar 

  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. Mearow, K. M., Mill, J. F., Freese, E., 1990. Neuron-glia interactions involved in the regulation of glutamine synthetase, Glia 3:385–392.

    PubMed  Google Scholar 

  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. 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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  14. Norenberg, M. D., 1994. Astrocyte responses to CNS injury, J. Neuropathol. Exp. Neurol. 53:213–220.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  16. Carney, J. M., and Floyd, R. A., 1991. Protection against oxidative damage to CNS by a-phenyl-tert-butyl nitrone (PBN) and other spintrap** agents: a novel series of nonlipid free radical scavengers, J. Mol. Neurosci. 3:47–57.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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. 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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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. 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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  27. Benjamin, A. M., 1983. Ammonia in metabolic reactions between neurons and glia.in 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.

Download references

Author information

Authors and Affiliations

  1. Inserm U 421, Faculté de Médecine, Hôpital Henri Mondor, 94010, Creteil cedex, France

    Ghislaine Le Prince, Christiane Fages, Thierry Lefrançois & Marcienne Tardy

  2. Laboratoire de Neuropathologie Raymond Escourolle, INSERM U 360, Association Claude Bernard, Hôpital de la Salpêtrière, bd de l'Hôpital, 75651, Paris cedex 13, France

    Pia Delaere

  3. Department de Médecine Expérimentale, Université Claude Bernard, 8, avenue Rockefeller, 69373, Lyon cedex 08, France

    Monique Touret & Marcelle Salanon

Authors
  1. Ghislaine Le Prince
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pia Delaere
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christiane Fages
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thierry Lefrançois
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Monique Touret
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marcelle Salanon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marcienne Tardy
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Le Prince, G., Delaere, P., Fages, C. et al. Glutamine synthetase (GS) expression is reduced in senile dementia of the Alzheimer type. Neurochem Res 20, 859–862 (1995). https://doi.org/10.1007/BF00969698

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00969698

Key Words

Search

Navigation