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186 Mechanisms of the cns depressing effects of organic solvents
Author(s) -
Tähti H.,
Engelke M.,
Vaalavirla L.
Publication year - 1996
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/0736-5748(96)80375-3
Subject(s) - citation , library science , psychology , information retrieval , computer science
Orally or parenterally administered L-cystine (cys) and N-acetylL-cyst&e are neurotoxic in infant animals in which they readily penetrate through the immature blood-brain barrier. We have shown earlier that cys also kills cultured neurons in a concentrationand time-dependent manner. The neurotoxicity of cys resembles that of glutamate and N-methyl-D-aspartate (NMDA) but the mechanism is open. It was now investigated with neuronal cultures, brain slices and synaptic membranes prepared from control and cys-treated 4day*Id rat pups. Cys enhanced the release of L-glutamate and D-aspartate from hippocampal slices and cultured cerehellar granule cells. It enhanced the glutamate (0.1 n&i) and NMDA (I mM) -evoked influx of %a2+ and the glutamate-evoked elevation of intracellular free Ca2’ in culhlred neurons and the NMDAinduced formation of cyclic GMP in hippocampal slices. Competitive and noncompetitive NMDA antagonists and Zn”, a blocker of the NMDA receptor-governed ionophore, prevented the potentiation of neuronal C!aZ+ influx by cys. Cys also inhibited glutamate uptake. The mechanism of cysteine neurotoxicity is thus complex, involving both preand postsynaptic interactions with glutamatergic NMDA receptormediated neurotransmission.