Akt and calcium-permeable AMPA receptor are involved in the effect of pinoresinol on amyloid β-induced synaptic plasticity and memory deficits

• Published in: Biochemical pharmacology Vol. 184; p. 114366
• Main Authors: Yu, Jimin, Cho, Eunbi, Kwon, Huiyoung, Jeon, Jieun, Seong Sin, Jae, Kwon Park, Jun, Kim, Ji-Su, Woong Choi, Ji, Jin Park, Se, Jun, Mira, Choon Lee, Young, Hoon Ryu, Jong, Lee, Jeongwon, Moon, Minho, Lee, Seungheon, Hyun Cho, Jong, Hyun Kim, Dong
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.02.2021
• Subjects: Akt; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer’s disease; Amyloid beta-Peptides - toxicity; Animals; Calcium-permeable AMPA receptor; Disease Models, Animal; Furans - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Lignans - pharmacology; Long-term potentiation; Long-Term Potentiation - drug effects; Male; Memory Disorders - drug therapy; Memory Disorders - etiology; Memory Disorders - pathology; Mice; Mice, Inbred Strains; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Peptide Fragments - toxicity; Pinoresinol; Proto-Oncogene Proteins c-akt - metabolism; Receptors, AMPA - metabolism; Akt; Alzheimer’s disease; Calcium-permeable AMPA receptor; Long-term potentiation; Pinoresinol
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2020.114366

[Display omitted] Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders characterized by memory deficits. Although no drug has given promising results, synaptic dysfunction-modulating agents might be considered potential candidates for alleviating this disorder. Pinoresinol, a lignan found in Forsythia suspensa, is a memory-enhancing agent with excitatory synaptic activation. In the present study, we tested whether pinoresinol reduces learning and memory and excitatory synaptic deficits in an amyloid β (Aβ)-induced AD-like mouse model. Pinoresinol enhanced hippocampal long-term potentiation (LTP) through calcium-permeable AMPA receptor, which was mediated by Akt activation. Moreover, pinoresinol ameliorated LTP deficits in amyloid β (Aβ)-treated hippocampal slices via Akt signaling. Oral administration of pinoresinol ameliorated Aβ-induced memory deficits without sensory dysfunction. Moreover, AD-like pathology, including neuroinflammation and synaptic deficit, were ameliorated by pinoresinol administration. Collectively, pinoresinol may be a good candidate for AD therapy by modulating synaptic functions.