Cholinergic Involvement and Synaptic Dynamin 1 Expression in Yokukansan‐mediated Improvement of Spatial Memory in a Rat Model of Early Alzheimer's Disease

The aim of this study was to investigate the effect of Yokukansan (YKS) on the impairment of spatial memory and cholinergic involvement in a rat model of early‐phase Alzheimer's disease (AD). In this model, rats underwent four‐vessel transient cerebral ischemia and then were treated with beta amyloid oligomers injected intracerebroventricularly once daily for 7 days. These animals showed memory impairment in an eight‐arm radial maze task without histological evidence of apoptosis but with a decrease in expression of hippocampal dynamin 1, an important factor in synaptic vesicle endocytosis. Oral administration of YKS for 2 weeks significantly increased the number of correct choices and decreased the number of error choices in the eight‐arm radial maze task (P < 0.05). Moreover, YKS significantly increased high K⁺‐evoked potentiation of acetylcholine (ACh) release (P < 0.05) and significantly increased the expression of dynamin 1 (P < 0.01) in the hippocampus. The ameliorative effect of YKS on spatial memory impairment in our rat model of early‐phase AD may be mediated in part by an increase in ACh release and modulation of dynamin 1 expression, leading to improved synaptic function. Future studies will determine whether YKS is similarly useful in the treatment of memory defects in patients diagnosed with early‐stage AD. Copyright © 2012 John Wiley & Sons, Ltd.