| First Author | Wang DS | Year | 2012 |
| Journal | Cell Rep | Volume | 2 |
| Issue | 3 | Pages | 488-96 |
| PubMed ID | 22999935 | Mgi Jnum | J:265970 |
| Mgi Id | MGI:6207310 | Doi | 10.1016/j.celrep.2012.08.022 |
| Citation | Wang DS, et al. (2012) Memory deficits induced by inflammation are regulated by alpha5-subunit-containing GABAA receptors. Cell Rep 2(3):488-96 |
| abstractText | Systemic inflammation causes learning and memory deficits through mechanisms that remain poorly understood. Here, we studied the pathogenesis of memory loss associated with inflammation and found that we could reverse memory deficits by pharmacologically inhibiting alpha5-subunit-containing gamma-aminobutyric acid type A (alpha5GABA(A)) receptors and deleting the gene associated with the alpha5 subunit. Acute inflammation reduces long-term potentiation, a synaptic correlate of memory, in hippocampal slices from wild-type mice, and this reduction was reversed by inhibition of alpha5GABA(A) receptor function. A tonic inhibitory current generated by alpha5GABA(A) receptors in hippocampal neurons was increased by the key proinflammatory cytokine interleukin-1beta through a p38 mitogen-activated protein kinase signaling pathway. Interleukin-1beta also increased the surface expression of alpha5GABA(A) receptors in the hippocampus. Collectively, these results show that alpha5GABA(A) receptor activity increases during inflammation and that this increase is critical for inflammation-induced memory deficits. |
