Gene expression profiling in the developing rat brain exposed to ketamine

Q. Shi, L. Guo, T. A. Patterson, S. Dial, Q. Li, N. Sadovova, X. Zhang, J. P. Hanig, M. G. Paule, W. Slikker, C. Wang

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Ketamine, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with accelerated neuronal apoptosis in the developing rodent brain. In this study, postnatal day (PND) 7 rats were treated with 20 mg/kg ketamine or saline in six successive doses (s.c.) at 2-h intervals. Brain frontal cortical areas were collected 6 h after the last dose and RNA isolated and hybridized to Illumina Rat Ref-12 Expression BeadChips containing 22,226 probes. Many of the differentially expressed genes were associated with cell death or differentiation and receptor activity. Ingenuity Pathway Analysis software identified perturbations in NMDA-type glutamate, GABA and dopamine receptor signaling. Quantitative polymerase chain reaction (Q-PCR) confirmed that NMDA receptor subunits were significantly up-regulated. Up-regulation of NMDA receptor mRNA signaling was further confirmed by in situ hybridization. These observations support our working hypothesis that prolonged ketamine exposure produces up-regulation of NMDA receptors and subsequent over-stimulation of the glutamatergic system by endogenous glutamate, triggering enhanced apoptosis in developing neurons.

Original languageEnglish (US)
Pages (from-to)852-863
Number of pages12
JournalNeuroscience
Volume166
Issue number3
DOIs
StatePublished - Mar 31 2010

Keywords

  • N-methyl-d-aspartate (NMDA) receptor
  • TaqMan
  • gene expression
  • ketamine
  • microarray

ASJC Scopus subject areas

  • Neuroscience(all)

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    Shi, Q., Guo, L., Patterson, T. A., Dial, S., Li, Q., Sadovova, N., Zhang, X., Hanig, J. P., Paule, M. G., Slikker, W., & Wang, C. (2010). Gene expression profiling in the developing rat brain exposed to ketamine. Neuroscience, 166(3), 852-863. https://doi.org/10.1016/j.neuroscience.2010.01.007