The protective role of astroglia in the early period of experimental lead toxicity in the rat

• Autorzy: Struzynska L
• Języki publikacji: EN

Abstrakty

EN

Although the clinical manifestations of lead (Pb) neurotoxicity are documented, the subcellular mechanisms of its action are still an open question. The purpose of this study was to assess the function of nerve ending particles after acute lead exposure and to investigate whether it exerts a toxic effect on astroglial functions. The studies were performed using the rodent model of acute lead toxicity. Cellular fractions were used in biochemical measurements - synaptosomes and glial plasmalemmal vesicles (GPV). Since a procedure for the isolation of the fraction of astroglial origin has been developed, it becomes possible to investigate lead-astroglia interactions after in vivo exposure. It is of importance because most of the studies concerning lead toxicity were performed using astroglial culture systems. It was found that the uptake of glutamate (Glu) to the synaptosomes was lowered and KCl-dependent release was increased, suggesting the impairment of glutamatergic transmission leading to the elevation of extracellular amino acid concentration. In contrast, glutamate uptake to the GPV fraction was significantly elevated. The activity of the marker enzyme - glutamine synthetase (GS) was also significantly increased in the GPV fraction. The activation of glial functions suggest a regulatory role for these cells in the early period of acute lead toxicity.

Słowa kluczowe

EN

cellular fraction; astrocyte; lead; glutamine synthetase; rat; glial plasmalemmal vesicle; synaptosomal fraction; astroglia; toxicity; glutamate uptake; neurotoxicity; protein measurement; gliosis

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2000
• Tom: 60
• Numer: 2
• Opis fizyczny: p.167-173,fig.

Twórcy

autor

Struzynska L

• Polish Academy of Sciences, 5 Pawinski St., 02-106 Warsaw, Poland

Bibliografia

• Aschner M., LoPachin R. M., Jr. (1993) Astrocytes: targets and mediators of chemical-induced ens injury. J. Toxicol. Environ. Health 38: 329-342.
• Bercovitz K., Laufer D. (1991) Lead release from human bones. International conference: heavy metals in the envi­ronment (Ed. J.G. Farmer). Edinbourgh, p. 123-126.
• Booth R.F., Clark J.B. (1978) A rapid method for the prepara­tion of relatively pure, metabolically competent synapto­somes from rat brain. Biochem. J. 176: 365-370.
• Cookman G.R., Hemmens S.E., Keane G.J., King W.B., Regan C.M. (1988) Chronic low level lead exposure preco­ciously induces rat glial development in vitro and in vivo. Neurosci. Lett. 86: 33-37.
• Daniels K.K., Vickroy T.W. (1998) Simultaneous isolation of glial and neuronal fractions from rat brain homogenates: comparison of high-affinity L-glutamate transport proper­ties. Neurochem. Res. 23: 103-113.
• Divac I., Fonum F., Storm-Mathisen J (1977) High affinity up­take of glutamate in terminals of corticostriatal axons. Na­ture 266: 377-378.
• Engle M.J., Volpe J.J. (1990) Glutamine synthetase activity of developing astrocytes is inhibited in vitro by very low con­centrations of lead. Dev. Brain Res. 55: 283-287.
• Flott B., Seifert W. (1991) Characterization of glutamate up­take systems in astrocyte primary cultures from rat brain. Glia 4: 293-304.
• Goyer R.A., Chisolm J.J. (1972) Lead. In: Metabolic contami­nants and human health (Ed. D.H.K. Lee). Academic Press, New York, p. 57-95.
• Heidinger V., Hicks D., Sahel J., Dreyfus H. (1999) Ability of retinal Mdller glial cells to protect neurons against excito- toxicity in vitro depends upon maturation and neuron-glial interactions. Glia 25: 229-239.
• Holtzman D., DeVries C., Nguyen H., Olson J., Bensch K. (1984) Maturation of resistance to lead encephalopathy: cellular and subcellular mechanisms. Neurotoxicology 5: 97-124.
• Holtzman D., Olson J.E., DeVries C., Bensh K. (1987) Lead toxicity on primary cultured cerebral astrocytes and cere­bellar granular neurons. Toxicol. Appl. Pharmacol. 89: 211-225.
• Lowry O.W., Rosenbrough N.J., Farr A.L., Randal R.J. (1951) Protein measurement with Folin phenol reagent. J. Biol. Chem. 193:265-275.
• Martinez-Hernandez A., Bell K.P., Norenberg M.D. (1977) Glutamine synthetase: glial localization in brain. Science 195: 1356-1358.
• Mennerick S., Benz A., Zorumski C.F. (1996) Components of glial responses to exogenous and synaptic glutamate in rat hippocampal microcultures. J. Neurosci. 16: 55-64.
• Mushak P. (1993) New directions in the toxicokinetics of human lead exposure. NeuroToxicology 14: 29-42.
• Nakamura Y., Iga K., Shibata T., Shudo M., Kataoka K. (1993) Glial plasmalemmal vesicles: a subcellular fraction from rat hippocampal homogenate distinct from synapto- somes. Glia 9: 48-56.
• Niklowitz W.J. (1977) Subcellular mechanisms in lead tox­icity: significance in childhood encephalopathy, neurologi­cal sequelae, and late dementias. In: Neurotoxicology (Eds. L. Roizin, H. Shiraki and N. Grevic). Raven Press, New- York, p. 289-298.
• Norenberg M.D. (1976) Reactive astrocytosis. In: The role of glia in neurotoxicity (Eds. M. Aschner and H.K. Kimelberg). CRC Press, New York, p. 93-107.
• Norenberg M.D. (1977) The distribution of glutamine synthe­tase in the central nervous system. J. Histochem. Cy- tochem. 27: 469-475.
• Pishak M.R., Phillips A.T. (1979) A modified radioisotopic assay for measuring glutamine synthetase activity in tissue extracts. Anal. Biochem. 94: 82-88.
• Ronnback L., Hansson E. (1992) Chronic encephalopathies induced by mercury or lead: aspects of underlying cellular and molecular mechanisms. British J. Ind. Med. 49: 233­240.
• Schousboe A., Svenneby G., Hertz L. (1977) Uptake and me­tabolism of glutamate in astrocytes cultured from dissoci­ated mouse brain hemispheres. J. Neurochem. 29: 999-1005.
• Sierra E.M., Tiffany-Castiglioni E. (1991) Reduction of glu­tamine synthetase activity in astroglia exposed in culture to low levels of inorganic lead. Toxicology 65: 295-304.
• Struzynska L., Walski M., Rafalowska U. (1999) The glial re­sponse in the acute lead-induced neurotoxicity in the rat. Acta Neurobiol. Exp. 59: 215. (Abstr. 17.8).
• Tiffany-Castiglioni E. (1993) Cell culture models for lead tox­icity in neuronal and glial cells. Neurotoxicology 14:513-536.
• Tiffany-Castiglioni E., Zmudzki J., Bratton G.R. (1986) Cel­lular targets of lead neurotoxicity: in vitro models. Toxico­logy 42: 303-305.
• Vernadakis A. (1988) Neuron-glia interactions. Int. Rev. Neurobiol. 30: 149-225.
• Veronesi B. (1992) The use of cell culture for evaluating neur­otoxicity. In: Neurotoxicology (Eds. H. Tilson and C. Mit­chell). Raven Press, New York, p. 21-49.