Cholinergic involvement and synaptic dynamin 1 expression in Yokukansan-mediated improvement of spatial memory in a rat model of early Alzheimer's disease.

Abstract

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.

• Authors: Naoki Uchida, Kotaro Takasaki, Yuri Sakata, Ai Nogami, Hiroshi Oishi, Takuya Watanabe, Taro Shindo, Nobuaki Egashira, Kaori Kubota, Shutaro Katsurabayashi, Kenichi Mishima, Michihiro Fujiwara, Ryoji Nishimura, Katsunori Iwasaki
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 27 Issue 7 Pg. 966-72 (Jul 2013) ISSN: 1099-1573 [Electronic] England
• PMID: 22888033 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 John Wiley & Sons, Ltd.

Chemical References

• Amyloid beta-Peptides
• Drugs, Chinese Herbal
• Yi-Gan San
• Dynamin I
• Acetylcholine

Topics

• Acetylcholine (metabolism)
• Administration, Oral
• Alzheimer Disease (drug therapy, metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Disease Models, Animal
• Drugs, Chinese Herbal (administration & dosage, therapeutic use)
• Dynamin I (metabolism)
• Hippocampus (drug effects, metabolism)
• Injections, Intraventricular
• Ischemic Attack, Transient (drug therapy)
• Male
• Maze Learning (drug effects, physiology)
• Memory Disorders (drug therapy, metabolism, pathology)
• Rats
• Rats, Wistar
• Synaptic Transmission (drug effects)