Results
In this study, we initially resynthesised a water soluble α5 GABAAR-selective compound NAM, α5-SOP002 and determined its selectivity using HEK293 cells lines stably expressing α5β2γ2-, α2β2γ2- or α1β2γ2-GABAARs. To identify changes of the expression pattern of α5 GABAAR during a disease that is characterised by cognitive deficits, we used an AD mouse model and wild-type mice at 10-12 months, when the typical hallmarks of AD in the hippocampus are present, including synaptic loss, accumulation of amyloid-β (Aβ) and proliferation of reactive astrocytes and microglia (Petrache et al., 2019; Saito et al., 2014). The effects of α5-SOP002 on inhibitory synaptic potentials recorded in the identified cells that co-expressed α5 GABAAR were investigated.
The development of the α5-SOP002