Microarray analysis of rat hippocampus exposed to excitotoxicity: reversal Na(+)/Ca(2+) exchanger NCX3 is overexpressed in glial cells

Hippocampus. 2012 Feb;22(2):128-40. doi: 10.1002/hipo.20869. Epub 2010 Oct 6.

Abstract

Multiple factors are involved in the glutamate-induced excitotoxicity phenomenon, such as overload of ionotropic and metabotropic receptors, excess Ca(2+) influx, nitric oxide synthase activation, oxidative damage due to increase in free radicals, and release of endogenous polyamine, among others. In order to attempt a more integrated approach to address this issue, we established, by microarray analysis, the hippocampus gene expression profiles under glutamate-induced excitotoxicity conditions. Increased gene expression is mainly related to excitotoxicity (CaMKII, glypican 2, GFAP, NCX3, IL-2, and Gmeb2) or with cell damage response (dynactin and Ecel1). Several genes that augmented their expression are related to glutamatergic system modulation, in particular with NMDA receptor modulation and calcium homeostasis (IL-2, CaMKII, acrosin, Gmeb2, hAChE, Slc83a, and SP1 factor). Conversely, among genes that diminished their expression, we found the Syngap 1, which is downregulated by CaMKII, and the MHC II, which is downregulated by glutamate. Changes observed in gene expression induced by monosodium glutamate (MSG) neonatal treatment in the hippocampus are consistent with the activation of the mechanisms that modulate NMDA receptor function as well as with the implementation of plastic response to cell damage and intracellular calcium homeostasis. Regarding this aspect, we report here that NCX3/Slc8a3, a Na(+)/Ca(2+) membrane exchanger, is highly expressed in astrocytes, both in vitro and in vivo, in response to glutamate-induced excitotoxicity. Hence, the results of this analysis present a broad view of the expression profile elicited by MSG neonatal treatment, and lead us to suggest the possible molecular pathways of action and reaction involved under this experimental model of excitotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Excitatory Amino Acids / pharmacology*
  • Gene Expression Profiling*
  • Glutamic Acid / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Immunohistochemistry
  • Neuroglia / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Rats
  • Rats, Wistar
  • Sodium-Calcium Exchanger / biosynthesis*

Substances

  • Excitatory Amino Acids
  • Slc8a3 protein, rat
  • Sodium-Calcium Exchanger
  • Glutamic Acid