Does an activation of RAR improve Alzheimer disease by the expression of transthyretin?

RAR 的激活是否可以通过转甲状腺素蛋白的表达来改善阿尔茨海默病？

• 批准号: 21700409
• 负责人: KITAOKA Kazuyoshi
• 金额: $ 2.25万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21700409/
• 关键词: 老化; アルツハイマー病; レチノイン酸; Adam10; トランスサイレチン; 神経科学; 学習; ビタミンA

I investigate the mechanism of anti-Alzheimer effect of retinoic acid receptor activation focused on the transthyretin (TTR), by using senescence accelerated (SAMP8) mice. As the results, the activation of RAR improves the memory function of SAMP8. However, the protein expression of TTR was not shown. On the other hands, Adam10 protein, which has α-secretase activity and correlates with neurogenesis, is significantly recovered by the RAR activation. The effect of Adam10-derivedα-secretase activity for amyloid beta is not clear because SAMP8 mice did not show the deposit of amyloid beta in this study. However, the expression of Hes5, which associates with neurogenesis, showed the significant increase in RAR-activated SAMP8 mice. Besides that, the expression of Adam10 and Hes5 are significantly correlated. The results in this study suggest that the RAR activation is improved memory function of SAMP8 by the recovery of Adam10 expression.

本研究以快速老化（SAMP 8）小鼠为实验对象，探讨了以甲状腺素运载蛋白（transthyretin，TTR）为中心的维甲酸受体激活对阿尔茨海默病的抗衰老作用机制。因此，RAR的激活改善了SAMP 8的记忆功能。然而，TTR的蛋白表达未显示。另一方面，具有α-分泌酶活性并与神经发生相关的Adam 10蛋白通过RAR激活而显著恢复。Adam 10衍生的α-分泌酶活性对β淀粉样蛋白的影响尚不清楚，因为在本研究中SAMP 8小鼠未显示β淀粉样蛋白的存款。然而，与神经发生相关的Hes 5的表达在RAR激活的SAMP 8小鼠中显示出显著增加。Adam 10和Hes 5的表达呈显著相关。本研究的结果表明RAR激活是通过恢复Adam 10表达来改善SAMP 8的记忆功能。

项目成果

Four-week administration of retinoic acid receptors antagonist LE540 at tenuates EEG delta power during sleep in mice

给予视黄酸受体拮抗剂 LE540 4 周可减弱小鼠睡眠期间的脑电图 delta 功率

• 发表时间: 2009
• 作者: 武藤淳;今井貴雄;馬渕洋;松崎由未;吉田一成;岡野栄之;Yoshimura T;北岡和義
• 通讯作者: 北岡和義

起立動作時における予測的な脳血流量,総頸動脈血流速度の変化

站立运动时脑血流量和颈总动脉血流速度的预测变化

• 发表时间: 2009
• 作者: Horisawa K.;Imai T.;Okano H.;Yanagawa H.;北岡和義
• 通讯作者: 北岡和義

Four-week administration of retinoic acid receptors antagonist LE540 attenuates EEG delta power during sleep in mice.

给予视黄酸受体拮抗剂 LE540 4 周会减弱小鼠睡眠期间的脑电图 delta 功率。

• 发表时间: 2009
• 作者: 吉村武;Jan Sedzik;池中一裕;Kitaoka K
• 通讯作者: Kitaoka K

Anticipatory changes in carotid blood flow velocity and cerebral blood flow preceds standing movement.

颈动脉血流速度和脑血流的预期变化先于站立运动。

• 发表时间: 2010
• 作者: Horisawa K;Imai T;Okano H;Yanagawa H.;吉村武;北岡和義
• 通讯作者: 北岡和義

Disturbance of rapid eye movement sleep in senescence- accelerated mouse prone/8 mice is improved by retinoic acid receptor agonist Am80 (Tamibarotene).

视黄酸受体激动剂Am80（他米巴罗汀）可改善衰老加速小鼠pron/8小鼠的快速动眼睡眠障碍。

• 发表时间: 2010
• 期刊: Neuroscience (In press)
• 作者: Horisawa K.;Imai T;Okano H;Yanagawa H;北岡和義
• 通讯作者: 北岡和義