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


Correspondence to: Naoki Uchida, Ph.D., Department of Psychiatry, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814–0180, Japan, Telephone: +81-92-801-1011 (ext. 3385), FAX: +81-92-863-3150



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.