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.
Department of Psychiatry, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan. naoki.uc@gmail.com
Naoki
N
Uchida
Kotaro
K
Takasaki
Yuri
Y
Sakata
Ai
A
Nogami
Hiroshi
H
Oishi
Takuya
T
Watanabe
Taro
T
Shindo
Nobuaki
N
Egashira
Kaori
K
Kubota
Shutaro
S
Katsurabayashi
Kenichi
K
Mishima
Michihiro
M
Fujiwara
Ryoji
R
Nishimura
Katsunori
K
Iwasaki
D000109:Acetylcholine / Q000378:metabolism; D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D034284:Dynamin I / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000188:drug therapy; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects
D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; C524644:Yi-Gan San; D034284:Dynamin I; D000109:Acetylcholine