Glutamine synthetase (GS) expression is reduced in senile dementia of the Alzheimer type
- 80 Downloads
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 WordsBlessed test score astrocyte classical senile plaque βA4 classical deposits
Unable to display preview. Download preview PDF.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.Google Scholar