Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairment

Fan Liu; Weiheng Yan; Chen Chen; Yubing Zeng; Yaru Kong; Xuejia He; Pei Pei; Shan Wang; Ting Zhang

doi:10.3389/fnmol.2024.1324458

Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairment

Front Mol Neurosci. 2024 Feb 22:17:1324458. doi: 10.3389/fnmol.2024.1324458. eCollection 2024.

Authors

Fan Liu^{1

2

3}, Weiheng Yan¹, Chen Chen², Yubing Zeng^{1

2}, Yaru Kong¹, Xuejia He⁴, Pei Pei², Shan Wang^{1

2

3

4}, Ting Zhang^{1

2

3

4}

Affiliations

¹ Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China.
³ Graduate School of Peking Union Medical College, Beijing, China.
⁴ Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China.

Abstract

Introduction: Chronic intermittent hypoxia (CIH) can negatively affect hippocampal function through various molecular mechanisms. Protein acetylation, a frequently occurring modification, plays crucial roles in synaptic plasticity and cognitive processes. However, the global protein acetylation induced by CIH in the hippocampus and its specific effects on hippocampal function and behavior remain poorly understood.

Methods: To address this gap, we conducted a study using liquid chromatography-tandem mass spectrometry to analyze the lysine acetylome and proteome of the hippocampus in healthy adult mice exposed to intermittent hypoxia for 4 weeks (as a CIH model) compared to normoxic mice (as a control).

Results: We identified and quantified a total of 2,184 lysine acetylation sites in 1,007 proteins. Analysis of these acetylated proteins revealed disturbances primarily in oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and glycolysis, all of which are localized exclusively to mitochondria. Additionally, we observed significant changes in the abundance of 21 proteins, some of which are known to be associated with cognitive impairments.

Discussion: This study helps to elucidate the molecular mechanisms underlying CIH-induced changes in protein acetylation in the hippocampus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hippocampal function, our findings contribute to a better understanding of the consequences of CIH-induced changes in protein acetylation in the hippocampus and the potential role of CIH in cognitive impairment.

Keywords: CIH; cognition; hippocampus; lysine acetylation; mitochondria.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Capital’s Funds for Health Improvement and Research (2022-2-1132), the Beijing Hospitals Authority’s Ascent Plan (DFL20221102), the Beijing Hospitals Authority Clinical Technology Innovation Program (XLMX 202110), the Public Service Development and Reform Pilot Project of Beijing Medical Research Institute (BMR2021-3), and the National Natural Science Foundation of China (82271193).