TY - JOUR
T1 - Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice
AU - Yamada, Marina
AU - Hayashida, Miki
AU - Zhao, Qi
AU - Shibahara, Naotoshi
AU - Tanaka, Ken
AU - Miyata, Takeshi
AU - Matsumoto, Kinzo
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Aim of the study: Yokukansan (YKS) is a Japanese traditional herbal medicine and has been used for the treatment of the behavioral and psychological symptoms of dementia (BPSD). The present study aimed to clarify the effects of YKS on learning and memory impairments, and its mechanisms of action in olfactory bulbectomized (OBX) mice, one of the animal models of Alzheimer's disease (AD). Materials and methods: OBX or sham-operated ddY mice were treated with YKS or donepezil (DPZ), a reference drug, and their cognitive performances were tested by the modified Y-maze test, novel object recognition test, and fear conditioning test to elucidate the spatial working memory, non-spatial short-term memory, and long-term memory, respectively. After completing the behavioral experiments, the expression level of cholinergic marker proteins and the activity of acetylcholinesterase (AChE) in the brain were analyzed by western blotting and Ellman's method, respectively. Results: OBX caused spatial working memory and non-spatial working memory impairments that were reversed by YKS and also by DPZ; however, YKS failed to affect the long-term memory deficits. Amelioration of the spatial working memory by YKS was reversible by scopolamine, a muscarinic receptor antagonist. YKS treatment reversed OBX-induced down-regulation of choline acetyltransferase and muscarinic muscarinic M 1 receptor expression without affecting muscarinic M 3 receptor expression or AChE activity. Conclusion: These results demonstrate that YKS improves short-term memory deficit caused by OBX and that the effect is at least partly mediated by muscarinic receptor stimulation and the normalization of central cholinergic systems. The present findings also suggest that YKS has a therapeutic effect not only on BPSD, but also on memory impairment of AD.
AB - Aim of the study: Yokukansan (YKS) is a Japanese traditional herbal medicine and has been used for the treatment of the behavioral and psychological symptoms of dementia (BPSD). The present study aimed to clarify the effects of YKS on learning and memory impairments, and its mechanisms of action in olfactory bulbectomized (OBX) mice, one of the animal models of Alzheimer's disease (AD). Materials and methods: OBX or sham-operated ddY mice were treated with YKS or donepezil (DPZ), a reference drug, and their cognitive performances were tested by the modified Y-maze test, novel object recognition test, and fear conditioning test to elucidate the spatial working memory, non-spatial short-term memory, and long-term memory, respectively. After completing the behavioral experiments, the expression level of cholinergic marker proteins and the activity of acetylcholinesterase (AChE) in the brain were analyzed by western blotting and Ellman's method, respectively. Results: OBX caused spatial working memory and non-spatial working memory impairments that were reversed by YKS and also by DPZ; however, YKS failed to affect the long-term memory deficits. Amelioration of the spatial working memory by YKS was reversible by scopolamine, a muscarinic receptor antagonist. YKS treatment reversed OBX-induced down-regulation of choline acetyltransferase and muscarinic muscarinic M 1 receptor expression without affecting muscarinic M 3 receptor expression or AChE activity. Conclusion: These results demonstrate that YKS improves short-term memory deficit caused by OBX and that the effect is at least partly mediated by muscarinic receptor stimulation and the normalization of central cholinergic systems. The present findings also suggest that YKS has a therapeutic effect not only on BPSD, but also on memory impairment of AD.
KW - Alzheimer's disease
KW - Cholinergic system
KW - Cognitive deficits
KW - Olfactory bulbectomy
KW - Yokukansan
UR - http://www.scopus.com/inward/record.url?scp=79957455834&partnerID=8YFLogxK
U2 - 10.1016/j.jep.2011.04.010
DO - 10.1016/j.jep.2011.04.010
M3 - 学術論文
C2 - 21513784
AN - SCOPUS:79957455834
SN - 0378-8741
VL - 135
SP - 737
EP - 746
JO - Journal of Ethnopharmacology
JF - Journal of Ethnopharmacology
IS - 3
ER -