title: Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice.
abstract: OBJECTIVE
  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).
  
  
  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 M₁ receptor expression without affecting muscarinic M₃ receptor expression or AChE activity.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Yamada
authors.forename: Miki
authors.initials: M
authors.lastname: Hayashida
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Shibahara
authors.forename: Ken
authors.initials: K
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
authors.forename: Kinzo
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D000077265:Donepezil; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005239:Fear; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D009830:Olfactory Bulb / Q000601:surgery; D008517:Phytotherapy; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D055441:Poria; D011976:Receptors, Muscarinic / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D004365:Drugs, Chinese Herbal; D007189:Indans; D010880:Piperidines; D011976:Receptors, Muscarinic; C524644:Yi-Gan San; D000077265:Donepezil; D012601:Scopolamine; D002795:Choline O-Acetyltransferase