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Alzheimer's Disease, Other Dementia, Aging

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Nobiletin, a citrus flavonoid, improves cognitive impairment in triple transgenic Alzheimer disease mouse model

  • P2-294
  • 青山 雄紀 / Yuki Aoyama:1 中島 晶 / Akira Nakajima:1 Shin Eun-Joo / Eun-Joo Shin:2 Kim Hyoung-Chun / Hyoung-Chun Kim:2 永井 拓 / Taku Nagai:1 横須賀 章人 / Akihito Yokosuka:3 三巻 祥浩 / Yoshihiro Mimaki:3 大泉 康 / Yasushi Ohizumi:4,5 山田 清文 / Kiyofumi Yamada:1 
  • 1:名古屋大院・医・医療薬学 / Dept Neuropsychopharmacol Hosp Pharm, Grad Sch Med, Nagoya Univ, Nagoya, Japan 2:Neuropsychopharmacol Toxicol Pro, Col Pharm, Kangwon Natl Univ, Chunchon, South Korea / Neuropsychopharmacol Toxicol Pro, Col Pharm, Kangwon Natl Univ, Chunchon, South Korea 3:東京薬科大院・医療衛生薬学・漢方資源応用学 / Lab Med Plant Sci, Sch Pharm, Tokyo Univ of Pharm Life Sci, Tokyo, Japan 4:静岡県立大院・薬・医薬生命化学 / Dept Mol Toxicol, Grad Sch Pharm Sci, Univ of Shizuoka, Shizuoka, Japan 5:東北福祉大・感性福祉研究所 / Kansei Fukushi Res Inst, Tohoku Fukushi Univ, Miyagi, Japan 

Alzheimer disease (AD) is a neurodegenerative disorder associated with age which represents the most common cause of dementia. Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, ameliorates learning and memory impairments in various animal models for cognitive deficits, including senescence-accelerated mouse prone 8. Triple transgenic (3ΧTg) AD mouse model develops amyloid beta (Aβ) and tau pathologies in a progressive manner, with a specific temporal and anatomic profile mimicking the pattern that takes place in the human brain with AD, and shows cognitive alterations characteristic of the disease. In the present study, we examined the effects of nobiletin on cognitive impairment and Aβ levels in 3ΧTg AD mice. 3ΧTg AD male mice (6 months of age) were intraperitoneally administered 10 or 30 mg/kg nobiletin for 3 months and subjected to behavioral analyses. Treatment of 3ΧTg AD mice with 30 mg/kg nobiletin ameliorated the impairment of working memory and recognition memory without affecting number of arm entries and total exploration time in Y-maze and novel object recognition test, respectively. Nobiletin also restored the increase in the soluble Aβ1-40 level in the brain of 3ΧTg AD mice in a dose-dependent manner. Together, the markedly beneficial effects of nobiletin represent a potentially useful treatment for ameliorating the cognitive deficits and accumulation of soluble Aβ1-40 in AD.

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