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

doi:10.1016/j.neuroscience.2010.01.007

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 journal › Article › peer-review

82 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 language	English (US)
Pages (from-to)	852-863
Number of pages	12
Journal	Neuroscience
Volume	166
Issue number	3
DOIs	https://doi.org/10.1016/j.neuroscience.2010.01.007
State	Published - Mar 31 2010

Keywords

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

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuroscience.2010.01.007

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title = "Gene expression profiling in the developing rat brain exposed to ketamine",

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.",

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

note = "Funding Information: This work was supported in part by an Interagency Agreement ( IAG 224-07-007 ) between NCTR/FDA and the National Institute for Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP), the Center for Drug Evaluation and Research (CDER)/FDA , and the National Institute of Child Health and Human Development (NICHD) . ",

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AU - Shi, Q.

AU - Guo, L.

AU - Patterson, T. A.

AU - Dial, S.

AU - Li, Q.

AU - Sadovova, N.

AU - Zhang, X.

AU - Hanig, J. P.

AU - Paule, M. G.

AU - Slikker, W.

AU - Wang, C.

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PY - 2010/3/31

Y1 - 2010/3/31

N2 - 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.

AB - 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.

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Gene expression profiling in the developing rat brain exposed to ketamine

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