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. 2023 Dec;41(6):589-603.
doi: 10.1007/s12640-023-00655-2. Epub 2023 Sep 5.

Glial Activation, Mitochondrial Imbalance, and Akt/mTOR Signaling May Be Potential Mechanisms of Cognitive Impairment in Heart Failure Mice

Yanan Wu  1   2 , Kaiyi Zhou  1   2 , Baiyang Liu  3 , Jindong Xu  1 , Liming Lei  1 , Jiaqi Hu  1 , Xiao Cheng  4   5   6 , Feng Zhong  7 , Sheng Wang  8   9
Affiliations

Glial Activation, Mitochondrial Imbalance, and Akt/mTOR Signaling May Be Potential Mechanisms of Cognitive Impairment in Heart Failure Mice

Yanan Wu et al. Neurotox Res. 2023 Dec.

Abstract

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.

Keywords: Akt/mTOR signaling; Cognitive impairment; Glial activation; Heart failure; Mitochondrial dynamics.

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