Heart failure (HF) is a major health burden worldwide, with approximately half of HF patients having a comorbid cognitive impairment (CI). However, it is still unclear how CI develops in patients with HF. In the present study, a mice model of heart failure was established by ligating the left anterior descending coronary artery. Echocardiography 1 month later confirmed the decline in ejection fraction and ventricular remodeling. Cognitive function was examined by the Pavlovian fear conditioning and the Morris water maze. HF group cued fear memory, spatial memory, and learning impairment, accompanied by activation of glial cells (astrocytes, microglia, and oligodendrocytes) in the hippocampus. In addition, the mitochondrial biogenesis genes TFAM and SIRT1 decreased, and the fission gene DRP1 increased in the hippocampus. Damaged mitochondria release excessive ROS, and the ability to produce ATP decreases. Damaged swollen mitochondria with altered morphology and aberrant inner-membrane crista were observed under a transmission electron microscope. Finally, Akt/mTOR signaling was upregulated in the hippocampus of heart failure mice. These findings suggest that activation of Akt/mTOR signaling, glial activation, and mitochondrial dynamics imbalance could trigger cognitive impairment in the pathological process of heart failure mice.

心力衰竭（HF）是全世界的主要健康负担，大约一半的心力衰竭患者患有认知障碍（CI）。然而，目前尚不清楚心衰患者如何发生 CI。本研究通过结扎左冠状动脉前降支建立小鼠心力衰竭模型。1个月后超声心动图证实射血分数下降和心室重构。通过巴甫洛夫恐惧调节和莫里斯水迷宫检查认知功能。高频组提示恐惧记忆、空间记忆和学习障碍，并伴有海马神经胶质细胞（星形胶质细胞、小胶质细胞和少突胶质细胞）的激活。此外，海马中线粒体生物发生基因TFAM和SIRT1减少，裂变基因DRP1增加。受损的线粒体会释放过量的 ROS，产生 ATP 的能力下降。在透射电子显微镜下观察到受损、肿胀的线粒体具有改变的形态和异常的内膜嵴。最后，心力衰竭小鼠海马体中的 Akt/mTOR 信号传导上调。这些发现表明，Akt/mTOR 信号传导的激活、神经胶质细胞的激活和线粒体动力学失衡可能会引发心力衰竭小鼠病理过程中的认知障碍。