Mechanisms of cognitive dysfunction in heart failure

心力衰竭认知功能障碍的机制

• 批准号: 23790862
• 负责人: ITO Koji
• 金额: $ 2.66万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790862/
• 关键词: 医療・福祉; 循環器・高血圧; 生理学; 脳・神経; 認知障害; 心不全; 圧負荷; 認知機能障害; シグマ受容体; 交感神経活動

We performed aortic banding + high salt loading or left coronary artery ligation, as heart failure models (HF) and sham operation (Sham) in mice. Compared with Sham, HF showed augmented sympathetic activity. The expression of brain sigma-1 receptor (S1R) was lower in HF than in Sham. To evaluate depressive-like behaviors, we recorded immobility time in tail suspension test, and the locomotor activity using a digital actophotometer . Compared with Sham, immobility time increased the daily variation of locomotor activity decreased in HF. In addition, to evaluate cognitive function, we performed the Y-Maze test. Compared with Sham, the spontaneous alteration was significantly decreased in HF. These changes were attenuated by intracerebroventricular infusion of PRE084, a selective S1R agonist. These results indicate that decreased brain S1R is reduced in mice with heart failure, which may contribute to mood and cognitive disorder in heart failure.

采用主动脉结扎+高盐负荷或左冠状动脉结扎的方法建立小鼠心衰模型（HF）和假手术（Sham）。与Sham相比，HF表现出增强的交感神经活性。脑内sigma-1受体（S1 R）的表达在HF组低于Sham组。为了评估抑郁样行为，我们记录了尾部悬吊试验中的不动时间，并使用数字式活动光度计记录了自发活动。与Sham组相比，HF组不动时间延长，自发活动日变化减少。此外，为了评估认知功能，我们进行了Y迷宫测试。与Sham相比，HF组的自发性改变明显减少。这些变化减弱脑室内灌注PRE 084，选择性S1受体激动剂。这些结果表明，心力衰竭小鼠的脑S1 R降低，这可能有助于心力衰竭的情绪和认知障碍。

项目成果

Deceased brain sigma-1 receptor contributes to mood and cognitive disorder in mice with heart failure.

死亡的大脑 sigma-1 受体会导致心力衰竭小鼠的情绪和认知障碍。

• 发表时间: 2012
• 作者: Maruyama S;Shibata R;Kikuchi R;Izumiya Y;Rokutanda T;Araki S;Kataoka Y;Ohashi K;Daida H;Kihara S;Ogawa H;Murohara T;Ouchi N;柿沼由彦,津田正之,岡崎佳代,秋山剛,有川幹彦,野口達哉,佐藤隆幸;伊藤浩司
• 通讯作者: 伊藤浩司

Sunagawa K Brain sigma-1 receptor stimulation improves mental disorder and cardiac function in mice with myocardial infarction

砂川 K 大脑 sigma-1 受体刺激可改善心肌梗塞小鼠的精神障碍和心脏功能

• 期刊: J Cradiovasc Pharmacol
• 作者: Ito K;Hirooka Y
• 通讯作者: Hirooka Y

Sunagawa K Decreased brain sigma-1 receptor contributes to the relationship between heart failure and depression

砂川 K 大脑 sigma-1 受体减少导致心力衰竭和抑郁症之间的关系

• 发表时间: 2012
• 期刊: Cradiovasc Res
• 作者: Ito K;Hirooka Y;Matsukawa R;Nakano M
• 通讯作者: Nakano M

ENaCs Contributes to Salt-induced Sympathoexcitation via Mineralocorticoid Receptor Activation and Insufficient Activation of CYP-EET Pathway in Mice with Pressure-overload

ENaCs 通过盐皮质激素受体激活和压力超负荷小鼠 CYP-EET 通路激活不足促进盐诱导的交感兴奋

• 发表时间: 2012
• 作者: Shinichi Okuda;伊藤浩司
• 通讯作者: 伊藤浩司

心不全における脳内シグマ受容体減少は交感神経活性を増強して心不全増悪を来すとともにうつ状態を助長する

心力衰竭时大脑中西格玛受体的减少会增强交感神经活动，从而加重心力衰竭并促进抑郁。

• 发表时间: 2011
• 作者: 伊藤浩司;廣岡良隆;砂川賢二
• 通讯作者: 砂川賢二