Sustained increase in α5GABAA receptor function impairs memory after anesthesia
Agnieszka A. Zurek, … , Eric W.R. Salter, Beverley A. Orser
Agnieszka A. Zurek, … , Eric W.R. Salter, Beverley A. Orser
Published November 3, 2014
Citation Information: J Clin Invest. 2014;124(12):5437-5441. https://doi.org/10.1172/JCI76669.
View: Text | PDF
Brief Report Neuroscience

Sustained increase in α5GABAA receptor function impairs memory after anesthesia

Abstract

Many patients who undergo general anesthesia and surgery experience cognitive dysfunction, particularly memory deficits that can persist for days to months. The mechanisms underlying this postoperative cognitive dysfunction in the adult brain remain poorly understood. Depression of brain function during anesthesia is attributed primarily to increased activity of γ-aminobutyric acid type A receptors (GABAARs), and it is assumed that once the anesthetic drug is eliminated, the activity of GABAARs rapidly returns to baseline and these receptors no longer impair memory. Here, using a murine model, we found that a single in vivo treatment with the injectable anesthetic etomidate increased a tonic inhibitory current generated by α5 subunit–containing GABAARs (α5GABAARs) and cell-surface expression of α5GABAARs for at least 1 week. The sustained increase in α5GABAAR activity impaired memory performance and synaptic plasticity in the hippocampus. Inhibition of α5GABAARs completely reversed the memory deficits after anesthesia. Similarly, the inhaled anesthetic isoflurane triggered a persistent increase in tonic current and cell-surface expression of α5GABAARs. Thus, α5GABAAR function does not return to baseline after the anesthetic is eliminated, suggesting a mechanism to account for persistent memory deficits after general anesthesia.

Authors

Agnieszka A. Zurek, Jieying Yu, Dian-Shi Wang, Sean C. Haffey, Erica M. Bridgwater, Antonello Penna, Irene Lecker, Gang Lei, Tom Chang, Eric W.R. Salter, Beverley A. Orser

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (2.73 MB)

Advertisement