Genkwanin Facilitates Long-term Potentiation via Calcium-permeable AMPA Receptor in the Hippocampus

Mild cognitive impairment (MCI) is regarded as a prodromal stage of Alzheimer’s disease (AD), and enhancing cognitive function during this period is a crucial strategy to delay progression to dementia. This study investigated the effects of genkwanin on hippocampal synaptic plasticity, particularly long-term potentiation (LTP), a cellular mechanism underlying learning and memory. Genkwanin significantly enhanced LTP in acute hippocampal slices, suggesting its potential role in improving memory function. Moreover, genkwanin increased phosphorylation of the GluA1 subunit of AMPA receptors, indicating a mechanism contributing to synaptic strengthening. Notably, the LTP-enhancing effect of genkwanin was abolished by IEM-1460, a selective antagonist of calcium-permeable AMPA receptors (CP-AMPARs). These results suggest that genkwanin facilitates hippocampal synaptic plasticity via the GluA1–CP-AMPAR pathway, providing a potential mechanism for cognitive improvement in early neurodegenerative conditions.