Memory Deficits Induced by Inflammation Are Regulated by α5-Subunit-Containing GABAA Receptors
Open accessAbstract
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 α5-subunit-containing γ-aminobutyric acid type A (α5GABA(A)) receptors and deleting the gene associated with the α5 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 α5GABA(A) receptor function. A tonic inhibitory current generated by α5GABA(A) receptors in hippocampal neurons was increased by the key proinflammatory cytokine interleukin-1β through a p38 mitogen-activated protein kinase signaling pathway. Interleukin-1β also increased the surface expression of α5GABA(A) receptors in the hippocampus. Collectively, these results show that α5GABA(A) receptor activity increases during inflammation and that this increase is critical for inflammation-induced memory deficits.
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Inhibition of α5 GABAAR attenuated memory deficits induced by inflammation.
“Inhibition of α5 GABAAR attenuated the memory deficits induced by inflammation51.”
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- Authors
- Wang, D.-S., Zurek, A. A., Lecker, I., Yu, J., Abramian, A. M., Avramescu, S., Davies, P. A., Moss, S. J., Lu, W.-Y., & Orser, B. A.
- Affiliations
- University of Toronto (CA)
- Tufts University (US)
- Western University (CA)
- Sunnybrook Health Science Centre (CA)
- Corresponding author
- Orser, Beverley A.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 2
- Issue
- 3
- Pages
- 488-496
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4391624
- OpenAlex
- W2109235361
- Cited by
- 182
- References
- 7
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 13 · 2023: 14 · 2022: 16 · 2021: 17 · 2020: 8 · 2019: 17 · 2018: 13 · 2017: 16 · 2016: 14 · 2015: 13 · 2014: 14 · 2013: 8
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (MOP:79428, MOP:38028)
- National Institute on Alcohol Abuse and Alcoholism (R21AA017938, AA017938)
- National Institute of Mental Health (R01MH097446)
- National Institute of Neurological Disorders and Stroke (R01NS051195, P01NS054900, R01NS048045, R01NS056359, R01NS081986, R03NS065725, R01NS047478)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- alpha5 GABA-A receptor, systemic inflammation, memory impairment, long-term potentiation, hippocampus, IL-1β, p38 MAPK signaling, receptor surface expression, inflammatory cytokines, neuroinflammation
- MeSH terms
- Animals, Hippocampus, Inflammation, Learning, Memory Disorders, Receptors, GABA-A, Synapses, Mice, Knockout, Mice, Interleukin-1beta
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