Acute neurotoxicity ofl-glutamate induced by impairment of the glutamate uptake system
We examined the effect of the glutamate uptake inhibitorl-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) on the neurotoxicity ofl-glutamate in organotypic cultures of rat spinal cord. Eighteen-day-old cultures were incubated with 500 μMl-glutamate, 1 mM PDC, or both. After 72 hours, the tissues were stained for acetylcholinesterase (AChE), and the ventral horn AChE-positive neurons (VHANs) analyzed using morphometry. Neitherl-glutamate nor PDC affected AChE staining, but in combination they produced markedly reduced AChE staining in the dorsal horn and a significant decrease in the number of VHANs (especially the smaller VHANs) as compared with the control. Moreover, treatment with 200 μM PDC for 2 weeks preferentially affected the smaller VHANs. The neurotoxicity ofl-glutamate plus PDC was blocked by the N-methyl-d-aspartate (NMDA) antagonist 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP).
Results suggest that glutamate uptake system has an important protective function in the aggravation of acute neuronal damage.
Key Wordsl-Glutamate glutamate transport neurotoxicity acetylcholinesterase organotypic explant culture spinal cord
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- 9.Garthwaite, J. 1985. Cellular uptake disguises action ofl-glutamate on N-methyl-d-aspartate receptors. With an appendix: diffusion of transported amino acids into brain slices. Br. J. Pharmac. 85:297–307.Google Scholar
- 20.Delfs, J., Friend, J., and Saroff, D. 1990. N-methyl-d-aspartic acid (NMDA) effects on spinal cord in organotypic roller tube culture.in F. C. Rose and F. H. Norris (eds.), ALS. New Advances in Toxicology and Epidemiology, pp. 273–281. Smith-Gordon, London.Google Scholar
- 25.Nishida, Y., Delfs, J., Saroff, D., Okazaki, S., and Saito, S. 1993. The neurotoxicity of glutamate agonists on ventral horn neurons in organotypic explant cultures of spinal cord. Can. J. Neurol. Sci. 20(S4): S82.Google Scholar