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アルツハイマー病、他の認知症、老化 2
Alzheimer's Disease, Other Dementia, Aging 2

開催日 2014/9/11
時間 15:00 - 16:00
会場 Room I(311+312)
Chairperson(s) 山田 麻紀 / Maki K. Yamada (東京大学 大学院医学系研究科 代謝生理化学分野 / Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Japan)
西村 正樹 / Masaki Nishimura (滋賀医科大学分子神経科学研究センター / Moleculer Neuroscience Research Center, Shiga University of Medical Science, Japan)

DR improves memory impairment in Alzheimer’s disease model mice, 5xFAD, and attenuates amyloid β-induced axonal atrophy

  • O1-I-4-3
  • Zhiyou Yang:1 Tomoharu Kuboyama:1 Chihiro Tohda:1 
  • 1:Div. of Neuromedical Sci., Institute of Natural Medicine, Univ. of Toyama, Toyama, Japan 

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. Current agents for AD are employed for symptomatic therapy and unfortunately insufficient to regain memory function. We consider axon/synapse formation activity is critical for the fundamental therapies of AD. Our previous studies have shown that the improvable activity against Aβ(25-35)-induced axonal atrophy in cultured cortical neurons correlates well to the effect on momory recovery in AD model mice.
In this study, 14 crude drugs were tested for evaluation of axonal regrowth activity. Double immunocytochemistry for phosphorylated NF-H and MAP2 was performed for quantification of axonal density. Among tested crude drugs, the water extract of DR* (1, 10 µg/ml) significantly increased axonal density in cortical neurons when adminstered 4 days after Aβ(25-35) treatment. For evaluation of in vivo activity, DR was adminstered to normal mice (ddY, male, 6 weeks old), and object recognition memory test was carried out with 48-h interval time. DR (500 mg/kg, 7 days, p.o.) administration significantly facilitated object recognition memory.
Using Alzheimer's disease model mice 5xFAD, memory improvement activity was investigated. DR (5, 50 and 500 mg/kg, p.o.) was administrated to 5xFAD mice for 21-31 days. Object recognition memory (1-h interval time), object location memory (1-h interval time) and episodic memory (10-min interval time each) were significantly improved by DR treatment in a dose-dependent manner. These results suggest that DR might be a promising drug to treat AD. We are now identifying major signal pathways of DR and active constituents in DR.

*A name of the crude drug is not open due to patent matters.

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