c-fos mRNA expression in rat cortical neurons during glutamate-mediated excitotoxicity

Toxicological Sciences : an Official Journal of the Society of Toxicology
Annamarie RogersD Clive Williams

Abstract

We have previously reported that exposure of mouse cerebellar granule cells (mCGCs) to excitotoxic concentrations of glutamate (Glu) induced a delayed, elevated, and sustained expression of c-fos mRNA, which was N-methyl-D-aspartic acid (NMDA) receptor mediated. In this study, the overstimulation of Glu receptors in primary rat cortical neurons by excitotoxins was used to study the cellular events triggering excitotoxic neuronal cell death, as the rat is the preferred species in regulatory and nonregulatory toxicological investigations. Exposure of rat cortical neurons to excitotoxins at high, toxic concentrations showed a change in the c-fos mRNA expression profile from a transient expression to one of sustained elevated levels. The excitotoxins induced much higher levels of c-fos mRNA in rat cortical neurons than in the mouse CGC system. Glu-induced c-fos mRNA expression, under excitotoxic conditions, was inhibited by D-2-amino-5-phosphonopentanoate (AP5) but not 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), indicating an event mediated by the NMDA subtype of Glu receptors. Using 12 compounds, which covered a range of nontoxic, toxic, and excitotoxic effects on rat cortical neurons, excitotoxicity was paralleled by a sustaine...Continue Reading

Citations

Sep 26, 2008·Archives of Toxicology·Gabriele Schmuck, Regine Kahl
Nov 6, 2013·Journal of Molecular Neuroscience : MN·Daniel Ortuño-SahagúnC Beas Zárate
Aug 17, 2006·Antioxidants & Redox Signaling·Michal Aharoni-SimonOren Tirosh
Jan 16, 2016·Journal of Molecular Neuroscience : MN·Yuki Kambe, Atsuro Miyata
Feb 27, 2010·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Germán L PerenoCarlos A Beltramino
Jun 11, 2010·Journal of Neurochemistry·Luisa de LemosAntoni Camins
Dec 19, 2013·Behavioral and Brain Functions : BBF·Jia LuoFeng Jin

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