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

Roger Griffiths, A Grieve, L Ritchie, M Scott, C Meredith

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 ([Ca2+](i)), 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 Ca2+ 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 [Ca2+](i) 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 Ca2+ 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.

Original languageEnglish
Pages (from-to)67-77
Number of pages11
JournalNeurochemical Research
Volume27
Issue number1-2
DOIs
Publication statusPublished - Feb 2002

Keywords

  • excitatory amino acids
  • excitotoxicity
  • c-fos mRNA
  • calcium
  • L-type calcium channels
  • cerebeller granule cells
  • HETEROMERIC NMDA RECEPTORS
  • ACID-INDUCED CYTOTOXICITY
  • MESSENGER-RNA EXPRESSION
  • D-ASPARTATE RECEPTOR
  • GENE-EXPRESSION
  • CALCIUM REGULATION
  • TRANSCRIPTION FACTORS
  • SIGNALING PATHWAYS
  • NEURONS
  • EXCITOTOXICITY

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this