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ePoster
NEGATIVE ALLOSTERIC MODULATORS OF Α5 GABA TYPE A RECEPTORS CAN PREVENT Β-AMYLOID-INDUCED PATHOLOGY IN AN <EM >EX VIVO </EM>MODEL OF ALZHEIMER’S DISEASE
Aoife O'Connelland 3 co-authors
University of Galway
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS03-08AM-135
Presentation
Date TBA
Board: PS03-08AM-135
Event Information
Poster Board
PS03-08AM-135
Poster
View posterAbstract
Alzheimer’s disease is a chronic neurodegenerative disease characterised by progressive cognitive impairment, a symptom hypothesised to arise from disruptions in the excitatory/inhibitory neurotransmission balance in the brain. While therapies targeting the excitatory side of this excitatory/inhibitory imbalance provide only symptomatic relief, approaches targeting the inhibitory gamma-aminobutyric acid (GABA) neurotransmission remain largely underexplored. In Alzheimer’s disease, the expression and activity of α5 GABA A receptors change, causing increased tonic inhibition and a disrupted excitatory/inhibitory balance, ultimately impairing cognitive processes. This study examined the therapeutic potential of two α5 GABA A receptor negative allosteric modulators, basmisanil and ONO-8590580, on preventing β-amyloid-induced pathology using microelectrode arrays and an acute ex vivo model of Alzheimer’s disease. Using acute hippocampal slices from male and female C57BL/6J mice, both basmisanil and ONO-8590580 prevented β-amyloid-induced deficits in long-term potentiation and β-amyloid-induced hyperexcitability in the CA1 pyramidal layer. These findings highlight the potential of selectively targeting α5 GABA type A receptors with α5 GABA A receptor negative allosteric modulators as a promising direction for the development of novel Alzheimer’s disease therapies.
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