Li Nuomin, Gao Yanan, Zhang Yongqian, Deng Yulin
Institute of Engineering Medicine, Beijing Institute of Technology, Beijing 100081, China.
School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
J Proteomics. 2023 May 15;279:104887. doi: 10.1016/j.jprot.2023.104887. Epub 2023 Mar 24.
Austere environment existing in tank, submarine and vessel has many risk factors including high temperature and humidity, confinement, noise, hypoxia, and high level of carbon dioxide, which may cause depression and cognitive impairment. However, the underlying mechanism is not fully understood yet. We attempt to investigate the effects of austere environment (AE) on emotion and cognitive function in a rodent model. After 21 days of AE stress, the rats exhibit depressive-like behavior and cognitive impairment. Compared with control group, the glucose metabolic level of the hippocampus is significantly decreased using whole-brain positron emission tomography (PET) imaging, and the density of dendritic spines of the hippocampus is remarkably reduced in AE group. Then, we employ a label-free quantitative proteomics strategy to investigate the differentially abundant proteins in rats' hippocampus. It is striking that the differentially abundant proteins annotated by KEGG enrich in oxidative phosphorylation pathway, synaptic vesicle cycle pathway and glutamatergic synapses pathway. The synaptic vesicle transport related proteins (Syntaxin-1A, Synaptogyrin-1 and SV-2) are down-regulated, resulting in the accumulation of intracellular glutamate. Furthermore, the concentration of hydrogen peroxide and malondialdehyde is increased while the activity of superoxide dismutase and complex I and IV of mitochondria is decreased, indicating that oxidative damage to hippocampal synapses is associated with the cognitive decline. The results of this study offer direct evidence, for the first time, that austere environment can substantially cause learning and memory deficits and synaptic dysfunction in a rodent model via behavioral assessments, PET imaging, label-free proteomics, and oxidative stress tests. SIGNIFICANCE: The incidence of depression and cognitive decline in military occupations (for example, tanker and submariner) is significantly higher than that of global population. In the present study, we first established novel model to simulate the coexisting risk factors in the austere environment. The results of this study offer the direct evidences, for the first time, that the austere environment can substantially cause learning and memory deficits by altering plasticity of the synaptic transmission in a rodent model via proteomic strategy, PET imaging, oxidative stress and behavioral assessments. These findings provide valuable information to better understand the mechanisms of cognitive impairment.
坦克、潜艇和舰艇中存在的恶劣环境有许多风险因素，包括高温高湿、空间密闭、噪音、缺氧和高二氧化碳水平，这些可能导致抑郁和认知障碍。然而，其潜在机制尚未完全明确。我们试图在啮齿动物模型中研究恶劣环境（AE）对情绪和认知功能的影响。经过21天的AE应激后，大鼠表现出抑郁样行为和认知障碍。与对照组相比，使用全脑正电子发射断层扫描（PET）成像显示海马体的葡萄糖代谢水平显著降低，且AE组海马体树突棘密度明显降低。然后，我们采用无标记定量蛋白质组学策略研究大鼠海马体中差异丰富的蛋白质。值得注意的是，经KEGG注释的差异丰富蛋白质富集于氧化磷酸化途径、突触小泡循环途径和谷氨酸能突触途径。与突触小泡运输相关的蛋白质（Syntaxin-1A、Synaptogyrin-1和SV-2）下调，导致细胞内谷氨酸积累。此外，过氧化氢和丙二醛浓度升高，而超氧化物歧化酶以及线粒体复合体I和IV的活性降低，表明海马体突触的氧化损伤与认知能力下降有关。本研究结果首次提供了直接证据，表明在啮齿动物模型中，恶劣环境可通过行为评估、PET成像、无标记蛋白质组学和氧化应激测试，显著导致学习和记忆缺陷以及突触功能障碍。意义：军事职业（如 tanker 和 submariner）中抑郁和认知能力下降的发生率显著高于全球人口。在本研究中，我们首次建立了新模型来模拟恶劣环境中共存的风险因素。本研究结果首次提供了直接证据，表明在啮齿动物模型中，恶劣环境可通过蛋白质组学策略、PET成像、氧化应激和行为评估改变突触传递可塑性，从而显著导致学习和记忆缺陷。这些发现为更好地理解认知障碍机制提供了有价值的信息。
