Gene expression profiling in the developing rat brain exposed to ketamine

• Published in: Neuroscience Vol. 166; no. 3; pp. 852 - 863
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 31.03.2010; Elsevier
• Subjects: Anesthetics, General - toxicity; Animals; Animals, Newborn; Biological and medical sciences; Brain - drug effects; Brain - growth & development; Brain - metabolism; Down-Regulation; Female; Fundamental and applied biological sciences. Psychology; gene expression; Gene Expression Profiling; In Situ Hybridization; ketamine; Ketamine - toxicity; Male; microarray; N-methyl- d-aspartate (NMDA) receptor; Neurology; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Rats; Receptors, N-Methyl-D-Aspartate - biosynthesis; Signal Transduction; TaqMan; Terminology as Topic; Up-Regulation; Vertebrates: nervous system and sense organs; hierarchical cluster analysis; TdT; N-methyl- d-aspartate; PND; PTEN; Q-PCR; deoxynucleotidyl transferase; metabotropic glutamate receptors; gene ontology; NF-κB; DEGs; TUNEL; TaqMan; KA; NMDA; ingenuity pathway analysis; postnatal day; nuclear factor kappa-light-chain-enhancer of activated B cells; iGluRs; HCA; RNA integrity numbers; GO; quantitative polymerase chain reaction; differentially expressed genes; terminal dUTP nick-end labelling; PCA; phosphatase and tensing homolog deleted on chromosome 10; microarray; ionotropic glutamate receptors; ketamine; RINs; IPA; N-methyl- d-aspartate (NMDA) receptor; gene expression; kainate receptors; principal component analysis; mGluRs; Rat; Rodentia; Central nervous system; Glutamate receptor; Gene expression; Encephalon; N-methyl-D-aspartate (NMDA) receptor; Vertebrata; Mammalia; Ketamine; Animal; Development; NMDA receptor
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.01.007

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.