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

Abstract

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.

Keywords: Akt; Alzheimer’s disease; Calcium-permeable AMPA receptor; Long-term potentiation; Pinoresinol.