Mechanisms of cognitive dysfunction in heart failure

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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.