title: Anesthesia-induced hypothermia mediates decreased ARC gene and protein expression through ERK/MAPK inactivation.
abstract: Several anesthetics have been reported to suppress the transcription of a number of genes, including Arc, also known as Arg3.1, an immediate early gene that plays a significant role in memory consolidation. The purpose of this study was to explore the mechanism of anesthesia-mediated depression in Arc gene and protein expression. Here, we demonstrate that isoflurane or propofol anesthesia decreases hippocampal Arc protein expression in rats and mice. Surprisingly, this change was secondary to anesthesia-induced hypothermia. Furthermore, we confirm in vivo and in vitro that hypothermia per se is directly responsible for decreased Arc protein levels. This effect was the result of the decline of Arc mRNA basal levels following inhibition of ERK/MAPK by hypothermia. Overall, our results suggest that anesthesia-induced hypothermia leads to ERK inhibition, which in turns decreases Arc levels. These data give new mechanistic insights on the regulation of immediate early genes by anesthesia and hypothermia.
authors.affiliation: Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Whittington
authors.forename: Alexis
authors.initials: A
authors.lastname: Bretteville
authors.forename: László
authors.initials: L
authors.lastname: Virág
authors.forename: Charles W
authors.initials: CW
authors.lastname: Emala
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Maurin
authors.forename: François
authors.initials: F
authors.lastname: Marcouiller
authors.forename: Carl
authors.initials: C
authors.lastname: Julien
authors.forename: Franck R
authors.initials: FR
authors.lastname: Petry
authors.forename: Noura B
authors.initials: NB
authors.lastname: El-Khoury
authors.forename: Françoise
authors.initials: F
authors.lastname: Morin
authors.forename: Jean
authors.initials: J
authors.lastname: Charron
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Planel
mesh_terms: D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism*; D054736:Elongation Factor 2 Kinase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007036:Hypothermia, Induced; D007530:Isoflurane / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D018685:Anesthetics, Inhalation; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D007530:Isoflurane; D054736:Elongation Factor 2 Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4
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