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Rat brain DNA transcript profile of halothane and isoflurane exposure

Pan, Jonathan Z.a; Wei, Huafenga; Hecker, James G.a; Tobias, John W.b; Eckenhoff, Roderic G.a; Eckenhoff, Maryellen Fazena

Pharmacogenetics and Genomics: March 2006 - Volume 16 - Issue 3 - pp 171-182
doi: 10.1097/01.fpc.0000189795.21770.08
Original Articles

Inhaled anesthetics produce many effects and bind to a large number of brain proteins, but it is not yet clear if this is accompanied by widespread changes in gene expression of the biological targets. Such changes in expression might implicate functionally important targets from the large pool of binding targets. Both rats and isolated primary cortical neurons were exposed to anesthetics and DNA oligonucleotide microarrays were used to detect and quantify transcriptional changes in neural tissue. Using analysis of variance with multiple testing correction, multiple exposures of rats to 0.8 MAC (minimum alveolar concentration) halothane only produced significant changes in a few metabolic genes. No significant in-vivo gene transcriptional response to 0.8 MAC isoflurane was detected. The use of primary cortical neurons allowed exposure to 3 MAC anesthetics without evidence of toxicity. Isoflurane altered several genes involved with neurotransmitter transport, signaling and cellular structure, whereas halothane produced few detectable changes in these cultured cells. Selected genes were confirmed by quantitative reverse transcription-polymerase chain reaction. Although indicating only a small degree of transcriptional regulation, these data implicate several plausible targets, including synaptic vesicle handling, that might contribute to drug action. In addition, the data show different gene expression profiles for the two inhaled anesthetics, suggesting unique pharmacological targets and mechanisms in each case.

aDepartment of Anesthesiology and Critical Care

bDepartment of Bioinformatics, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA

Correspondence and requests for reprints to Maryellen Fazen Eckenhoff, Department of Anesthesiology and Critical Care, 305 John Morgan, 3620 Hamilton Walk, University of Pennsylvania Health Systems, Philadelphia, PA 19104, USA

Tel: +1 215 662 3705; fax: +1 215 349 5708;

e-mail: eckenhom@uphs.upenn.edu

Sponsorship: This study was supported by NIGMS 51595 and the Austin Lamont Endowment to the Department of Anesthesiology and Critical Care, University of Pennsylvania.

Received 8 August 2005 Accepted 13 October 2005

© 2006 Lippincott Williams & Wilkins, Inc.