Hyperoside improves learning and memory deficits by amyloid β1-42 in mice through regulating synaptic calcium-permeable AMPA receptors

• Published in: European journal of pharmacology 2022-09, Vol.931, p.175188-175188, Article 175188
• Main Authors: Yi, Jee Hyun, Moon, Somin, Cho, Eunbi, Kwon, Huiyoung, Lee, Seungjin, Jeon, Jieun, Park, A Young, Lee, Ye Hee, Kwon, Kyoung Ja, Ryu, Jong Hoon, Jeon, Se Jin, Shin, Chan Young, Shim, Sang Hee, Kim, Dong Hyun
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid β; Calcium permeable AMPA receptor; Hyperoside; Long-term potentiation; PKA
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2022.175188

Alzheimer's disease (AD) is the most common degenerative disease and is indicative of dementia. The cerebral accumulation of amyloid β (Aβ), a crucial factor in AD, initiates synaptic and cognitive dysfunction. Therefore, the elevation of synaptic and cognitive functions may help manage dementia in AD. In this study, we suggest hyperoside as a synaptic function- and memory-enhancing agent. Hyperoside enhanced learning and memory in passive avoidance and object recognition tasks. Hyperoside facilitated synaptic long-term potentiation (LTP) in acute hippocampal slices. IEM-1460, a calcium-permeable amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR) antagonist, blocked the facilitation effect of hyperoside. Hyperoside also induced N-methyl-d-aspartate receptor (NMDAR)-independent LTP, which was blocked by IEM-1460, suggesting the involvement of CP-AMPARs in the synaptic effects of hyperoside-mediated LTP. PKI (a PKA inhibitor) or SQ22536 (adenylyl cyclase, an AC inhibitor) blocked hyperoside-facilitated LTP and hyperoside-induced NMDAR-independent LTP. Hyperoside-enhanced learning and memory were blocked by IEM-1460, suggesting the involvement of CP-AMPARs in the effect of hyperoside on learning and memory. Finally, hyperoside ameliorated Aβ-induced memory impairments in an AD mouse model. These results suggest that hyperoside enhances learning and memory, and this may be due to the effect of CP-AMPARs.