Propofol induces MAPK/ERK cascade dependant expression of cFos and Egr-1 in rat hippocampal slices

Authors

Srivatsan Kidambi, New York Methodist HospitalFollow
Joel Yarmush, New York Methodist Hospital
Yevgeny Berdichevsky, Shriners Hospitals for Children and Harvard Medical School
Sangeetha Kamath, New York Methodist Hospital
Wayne Fong, New York Methodist Hospital
Joseph SchianodiCola, New York Methodist Hospital

Date of this Version

2010

Citation

Kidambi et al.: Propofol induces MAPK/ERK cascade dependant expression of cFos and Egr-1 in rat hippocampal slices. BMC Research Notes 2010 3:201; doi:10.1186/1756-0500-3-201

Comments

Copyright 2010 Kidambi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License

Abstract

Background: Propofol is a commonly used intravenous anesthetic agent, which produce rapid induction of and recovery from general anesthesia. Numerous clinical studies reported that propofol can potentially cause amnesia and memory loss in human subjects. The underlying mechanism for this memory loss is unclear but may potentially be related to the induction of memory-associated genes such as c-Fos and Egr-1 by propofol. This study explored the effects of propofol on c-Fos and Egr-1 expression in rat hippocampal slices.

Findings: Hippocampal brain slices were exposed to varying concentrations of propofol at multiple time intervals. The transcription of the immediate early genes, c-Fos and Egr-1, was quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). MAPK/ERK inhibitors were used to investigate the mechanism of action. We demonstrate that propofol induced the expression of c-Fos and Egr-1 within 30 and 60 min of exposure time. At 16.8 μM concentration, propofol induced a 110% increase in c-Fos transcription and 90% decrease in the transcription of Egr-1. However, at concentrations above 100 μM, propofol failed to induce expression of c-Fos but did completely inhibit the transcription of Egr-1. Propofol-induced c-Fos and Egr-1 transcription was abolished by inhibitors of RAS, RAF, MEK, ERK and p38-MAPK in the MAPK/ERK cascade.

Conclusions: Our study shows that clinically relevant concentrations of propofol induce c-Fos and down regulated Egr-1 expression via an MAPK/ERK mediated pathway. We demonstrated that propofol induces a time and dose dependant transcription of IEGs c-Fos and Egr-1 in rat hippocampal slices. We further demonstrate for the first time that propofol induced IEG expression was mediated via a MAPK/ERK dependant pathway. These novel findings provide a new avenue to investigate transcription-dependant mechanisms and suggest a parallel pathway of action with an unclear role in the activity of general anesthetics.