Differential mechanisms of glutamate-stimulated perturbations in the kinetics of c-fos mRNA induction are associated with maturation of cerebellar granule cells in primary culture
article
In further exploring proposals for the measurement of early gene (c-fos mRNA) levels as a predictive index for in vitro excitotoxicity, this study, using immature (2 days in vitro) cultures of mouse cerebellar granule cells as an experimental model system, was undertaken to determine the effect of glutamate (Glu) i) in stimulating increases in intracellular free-calcium ([Ca<sup>2+</sup>]<sub>i</sub>), ii) on cell viability and iii) on induction of steady-state c-fos mRNA levels. In parallel experiments the action of agents (viz. 55 mM KCl and the calcium ionophore, A23187) that mediate Ca<sup>2+</sup> entry into cells via different routes was also evaluated. Glu was unable to induce excitotoxicity in granule cells at this stage of development in culture, but did stimulate a concentration-dependent and marked increase in [Ca<sup>2+</sup>]<sub>i</sub> levels while also mediating a dramatic concentration-dependent perturbation in the kinetics of c-fos mRNA induction that appeared to arise solely from NMDA receptor-mediated Ca<sup>2+</sup> influx. The results are presented in comparison to the actions of KCl and A23187 and considered in relation to earlier studies undertaken using mature (7 days in vitro) cultures of cerebellar granule cells.
Topics
C-fos mRNACalciumCerebellar granule cellsExcitatory amino acidExcitotoxicityL-type calcium channelsCalcimycinCalcium ionophoreGlutamic acidN methyl dextro aspartic acid receptorNifedipinePotassium chlorideAnimal cellBrain cellBrain depth stimulationCalcium cell levelCell cultureCell maturationCell transportCell viabilityConcentration responseControlled studyCytotoxicityGene inductionMouseNonhumanOncogene c fosPriority journalProtein analysisSteady stateTransport kineticsAnimalsCalciumCell AgingCell SurvivalCells, CulturedCerebellumGlutamic AcidIntracellular MembranesKineticsMiceMice, Inbred StrainsNeuronsOsmolar ConcentrationProto-Oncogene Proteins c-fosRNA, MessengerTime FactorsAnimalia
TNO Identifier
87835
Source
Neurochemical Research, 27(1/2), pp. 67-77.
Pages
67-77
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