Memory deficits induced by inflammation are regulated by α5 subunit-containing GABA
Tuesday, Oct 16, 2012, 1:00 PM - 2:00 PM
, A. A. ZUREK
, I. LECKER
, A. M. ABRAMIAN
, S. AVRAMESCU
, P. A. DAVIES
, S. J. MOSS
, W.-Y. LU
, B. A. ORSER
Anesthesia, Univ. of Toronto, Toronto, ON, Canada;
Neurosci., Tufts Univ., Boston, MA;
Neuroscience, Physiol. and Pharmacol., Univ. Col., London, United Kingdom;
Physiol. and Pharmacol., Univ. of Western Ontario, London, ON, Canada;
Anesthesia, Sunnybrook Hlth. Sci. Ctr., Toronto, ON, Canada
Systemic inflammation causes learning and memory deficits through complex mechanisms that remain poorly understood. Here, we studied the pathogenesis of memory loss associated with acute inflammation and found that α5 subunit-containing γ-aminobutyric acid type A (α5GABA
) receptors are downstream mediators of inflammation-induced memory deficits. Acute inflammation attenuates long-term potentiation, a synaptic correlate of memory; and this effect was reversed by deleting the gene for the α5 subunit or by pharmacologically inhibiting α5GABA
receptor activity. The pro-inflammatory cytokine interleukin-1β (IL-1β) increases the tonic current generated by α5GABA
receptors through a p38 MAPK signaling pathway in hippocampal neurons. IL-1β also increases the surface expression of these receptors in the hippocampus. Furthermore, inflammation-induced fear-associated memory loss was attenuated by genetically and pharmacologically inhibiting α5GABA
receptor activity. Together, the results show that enhanced α5GABA
receptor activity contributes to inflammation-induced memory deficits and these receptors are potential therapeutic targets for attenuating memory deficits.
CIHR Operating Grants MOP-38028 and MOP-79428 to Berveley A. Orser
[Authors]. [Abstract Title]. Program No. XXX.XX. 2012 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2012. Online.
2012 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
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