生命早期炎症小鼠模型海马体的蛋白质组和磷酸蛋白组综合分析

IF 2.2 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Neuroimmunomodulation Pub Date : 2023-01-01 Epub Date: 2023-01-04 DOI:10.1159/000527975
Xin-Miao Wu, Yu-Zhu Gao, Ting-Ting Zhu, Han-Wen Gu, Jian-Hua Tong, Jie Sun, Jian-Jun Yang, Mu-Huo Ji
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引用次数: 0

摘要

导言:生命早期的炎症是青春期和成年后患神经精神疾病的一个风险因素,但其潜在机制仍然难以捉摸。在本研究中,我们对海马进行了蛋白质组和磷酸化蛋白质组的综合分析,以确定生命早期炎症诱发认知障碍的潜在分子机制:雌性和雄性小鼠在出生后第10天(P10)腹腔注射100 μg/kg脂多糖(LPS)。行为测试包括开阔地、高架迷宫和Y迷宫测试,分别在出生后第39天、第40天和第41天进行。行为测试结束后,雄性小鼠被处死。在P42收获全脑组织和海马,进行蛋白质组、磷酸蛋白组、Western印迹和高尔基体染色:结果:根据Y-迷宫试验的评估,早期LPS暴露会诱发雄性小鼠的认知障碍,但不会诱发雌性小鼠的认知障碍。因此,对雄性小鼠进行了以下生化测试。通过蛋白质组分析,LPS 组有 13 种蛋白质表现出不同的表达。其中,9 种蛋白质上调,4 种蛋白质下调。磷酸蛋白组分析共鉴定出 518 个磷酸肽,与对照组相比,LPS 组有 316 个磷酸肽上调,202 个磷酸肽下调。此外,KEGG分析表明,生命早期暴露于LPS会影响谷氨酸能突触和神经活性配体与受体的相互作用,而这与突触功能和能量代谢有关。早期LPS暴露后,脑蛋白i3(Bri3)水平升高、PSD-95和mGLUR5水平降低以及树突棘丢失进一步证实了蛋白质组学和磷酸化蛋白质组学分析的结果:我们的研究结果表明,神经炎症和突触受损可能与早期炎症诱导的认知障碍有关。我们的研究结果表明,神经炎症和突触受损可能与生命早期炎症诱导的认知障碍有关。
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Integrated Proteomic and Phosphoproteomic Analysis of the Hippocampus in a Mouse Model of Early Life Inflammation.

Introduction: Inflammation in early life is a risk factor for the development of neuropsychiatric diseases later in adolescence and adulthood, yet the underlying mechanism remains elusive. In the present study, we performed an integrated proteomic and phosphoproteomic analysis of the hippocampus to identify potential molecular mechanisms of early life inflammation-induced cognitive impairment.

Methods: Both female and male mice received a single intraperitoneal injection of 100 μg/kg lipopolysaccharide (LPS) on postnatal day 10 (P10). Behavioral tests, including open field, elevated plus-maze, and Y-maze tests, were performed on P39, P40, and P41, respectively. After behavioral tests, male mice were sacrificed. The whole brain tissues and the hippocampi were harvested on P42 for proteomic, phosphoproteomic, Western blot, and Golgi staining.

Results: Early life LPS exposure induced cognitive impairment in male mice but not in female mice, as assessed by the Y-maze test. Therefore, following biochemical tests were conducted on male mice. By proteomic analysis, 13 proteins in LPS group exhibited differential expression. Among these, 9 proteins were upregulated and 4 proteins were downregulated. For phosphoproteomic analysis, a total of 518 phosphopeptides were identified, of which 316 phosphopeptides were upregulated and 202 phosphopeptides were downregulated in the LPS group compared with the control group. Furthermore, KEGG analysis indicated that early life LPS exposure affected the glutamatergic synapse and neuroactive ligand-receptor interaction, which were associated with synaptic function and energy metabolism. Increased level of brain protein i3 (Bri3), decreased levels of PSD-95 and mGLUR5, and dendritic spine loss after early life LPS exposure further confirmed the findings of proteomic and phosphoproteomic analysis.

Conclusions: Our findings demonstrated that neuroinflammation and impaired synapse may be involved in early life inflammation-induced cognitive impairment. Future studies are required to confirm our preliminary results.

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来源期刊
Neuroimmunomodulation
Neuroimmunomodulation 医学-免疫学
CiteScore
3.60
自引率
4.20%
发文量
35
审稿时长
>12 weeks
期刊介绍: The rapidly expanding area of research known as neuroimmunomodulation explores the way in which the nervous system interacts with the immune system via neural, hormonal, and paracrine actions. Encompassing both basic and clinical research, ''Neuroimmunomodulation'' reports on all aspects of these interactions. Basic investigations consider all neural and humoral networks from molecular genetics through cell regulation to integrative systems of the body. The journal also aims to clarify the basic mechanisms involved in the pathogenesis of the CNS pathology in AIDS patients and in various neurodegenerative diseases. Although primarily devoted to research articles, timely reviews are published on a regular basis.
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