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• W2018168566 abstract "Abstract: Exposure of cultured cerebellar granule neurons to subtoxic concentrations of N-methyl-d-aspartate (NMDA) has been shown previously to result in a neuroprotective state, as measured by subsequent exposure to toxic concentrations of glutamate. In the present study, we have further characterized the excitoprotective actions of NMDA in these neurons. NMDA-induced excitoprotection was concentration dependent (EC50∼30 µM) and time dependent, with maximal protection observed following 16 h of preexposure to NMDA. NMDA-induced excitoprotection did not require continuous exposure to NMDA, as a 4-h preincubation was sufficient to induce full excitoprotection when measured 8 h later. Maximal protection was manifest as a “right shift” in the concentration-response relationship for glutamate toxicity of approximately three orders of magnitude (EC50∼30 µM in untreated neurons compared with ≥50 mM in NMDA-treated neurons). After removal of NMDA, complete reversal of the excitoprotective state was observed by 48 h (t1/2≈24 h). The ability of NMDA to induce excitoprotection was observed in neurons maintained for up to 14 days in vitro (DIV) [postnatal day (PND) 22], but was absent at 21 and 32 DIV (PND 29–40), despite little to no difference in the toxicity of glutamate at any DIV examined. Preexposure of cerebellar granule neurons to a maximally excitoprotective concentration of NMDA (50 µM) failed to alter the density of NMDA receptors measured by the specific binding of [3H]MK-801. Moreover, the immediate elevation in intracellular free calcium concentration ([Ca2+]i) induced by glutamate exposure and measured by microfluorimetry and the Ca2+-sensitive indicator fura-2 was similar in NMDA-pretreated and untreated neurons. As reported previously, NMDA-induced excitoprotection in cerebellar granule neurons was, however, reversed by coincubation with the protein synthesis inhibitor cycloheximide. Taken together, these data suggest that NMDA receptor-mediated excitoprotection in cerebellar granule neurons is mediated via both a transcriptionally directed and a developmentally regulated postreceptor mechanism(s)." @default.
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• W2018168566 date "2002-11-23" @default.
• W2018168566 modified "2023-09-26" @default.
• W2018168566 title "Characterization of the Excitoprotective Actions of N-Methyl-d-Aspartate in Cultured Cerebellar Granule Neurons" @default.
• W2018168566 doi "https://doi.org/10.1046/j.1471-4159.1995.65031069.x" @default.
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