期刊
NEUROSCIENCE
卷 166, 期 3, 页码 852-863出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2010.01.007
关键词
ketamine; gene expression; microarray; Taq Man; N-methyl-D-aspartate (NMDA) receptor
资金
- NCTR/FDA [IAG 224-07-007]
- National Institute for Environmental Health Sciences (NIEHS) [IAG 224-07-007]
- Center for Drug Evaluation and Research (CDER)IFDA
- National Institute of Child Health and Human Development (NICHD)
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 Bead Chips 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 upregulated. 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. Published by Elsevier Ltd on behalf of IBRO.
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