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Ameliorative effects of yokukansan, a traditional Japanese medicine, on learning and non-cognitive disturbances in the Tg2576 mouse model of Alzheimer's disease

Bibliographic

Year of Publication:
2009
Contact PI Name:
Masahiro Tabuchi
Contact PI Affiliation:
Tsumura Research Laboratories, Tsumura & Co., Ami-machi, Inashiki-gun, Ibaraki, Japan
Co-Authors:
Takuji Yamaguchi, Seiichi Iizuka, Sachiko Imamura, Yasushi Ikarashi, Yoshio Kase
Primary Reference (PubMED ID):
Funding Source:
Not Reported
Study Goal and Principal Findings:

Aim of this study: Aim of the present study is to clarify the effects of yokukansan (TJ-54) on learning and non-cognitive disturbances in the Tg2576 mouse expressing the human form of the APP695SWE (APP-Tg mice), which is considered to be an animal model of Alzheimer's disease.

Materials and methods: Powdered diets containing 0.5 and 1.0% TJ-54 were given to the mice for 10 months (from 5 to 15 months old). The Morris water-maze test, elevated plus-maze test, and open-field test were performed for evaluation of learning and non-cognitive disturbances.

Results: Treatment with 1.0% TJ-54 for 5 months shortened the time it took for APP-Tg positive (+) mice to reach the platform in the Morris water-maze test. In the elevated plus-maze test, treatment with 1.0% TJ-54 for 2 months significantly reduced the increased number of entries and the time spent in open arms observed in APP-Tg(+) mice. In an open-field test, treatment of 1.0% TJ-54 for 9 months significantly suppressed the increase in locomotion observed in APP-Tg(+) mice.

Conclusion: These results suggest the possibility that TJ-54 ameliorates learning deficits and non-cognitive defects including a decrease in the anxiety (or disinhibition) and an increase in locomotor activity (hyperactivity) observed in APP-Tg(+) mice.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
Yokukansan
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Morris Water Maze
Elevated Plus Maze
Open Field Test
Motor Function
Locomotor Activity
Histopathology
beta Amyloid Load
beta Amyloid Deposits
Biochemical
Brain-Formic Acid Soluble beta Amyloid Peptides
Brain-Detergent Soluble beta Amyloid Peptides
Brain-Detergent Insoluble beta Amyloid Peptides
Immunochemistry
Amyloid Plaque Size
Amyloid Plaques
Toxicology
Anxiety