BRAIN RESEARCH BULLETIN
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2022
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IF 3.715
Lin Bai,Yingying Wu,Ruike Wang,Rundong Liu,Mengchen Liu,Qiong Li,Yue Ba,Huizhen Zhang,Guoyu Zhou,Fangfang Yu,Hui Huang
As a ubiquitous toxic heavy metal, lead (Pb) exposure is known to be implicated in the onset and development of neurodegenerative diseases which may cause more serious health hazards with age and the accumulation of Pb in the body. Autophagy is the main degradation route for abnormal aggregated proteins and damaged cell organelles. Here, we aimed to study the effects of adolescent Pb exposure on autophagy at different life nodes. In this study, we developed a time-series model of Pb exposure in mice and randomly divided 4-week-old male C57BL/6 mice into six groups (4 C, 13 C, 16 C, 4Pb, 13Pb and 16Pb). Mice in Pb groups was consumed deionized water containing 0.2 % Pb(Ac) 2 for 3 months and then reared to anticipated life nodes, while the control group consumed deionized water. Western blot and Real-time qPCR were used to assess the effects of developmental Pb exposure on individual components of the autophagy machinery and modulation of microtubule-associated protein 1 light chain 3 (LC3) at each age stage. Our results showed that Pb exposure during adolescence reduced the p-mTOR/mTOR ratios with enhanced expression of Beclin-1, Atg12 and Atg7in both the hippocampus (HPC) and prefrontal cortex (PFC) of senescent mice while upregulation of LC3II/LC3I ratios and p62 suggested that autophagy mediates degradation was interrupted. Overall, we confirm that Pb exposure during adolescence promotes autophagic processes in the aged mice brain and that autophagic degradation is hindered, ultimately leading to a failure of autophagic degradation.
研究领域:
毒理学
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神经科学
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分子生物学
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发育生物学
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衰老研究
✓ 已验证
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2024
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IF 4.2
Tingting Wang,Xia Wu,Xiaoli Zhao,Jiaqi Li,Jian Yu,Maozheng Sheng,Mingyuan Gao,Yutang Cao,Jiawen Wang,Xiaozhen Guo,Kai Zeng
Purpose Postoperative cognitive dysfunction (POCD) is a central nervous system complication that occurs after anesthesia, particularly among the elderly. However, the neurological pathogenesis of postoperative cognitive dysfunction remains unclear. The aim of this study was to evaluate the effects of sevoflurane exposure on serum metabolites and hippocampal gene expression in elderly patients and aging mice by metabolomics and transcriptomic analysis and to explore the pathogenesis of sevoflurane induced POCD.Patients and Methods Human serum samples from five patients over 60 years old were collected before sevoflurane anesthesia and 1 hour after anesthesia. Besides, mice aged at 12 months (n=6 per group) were anesthetized with sevoflurane for 2 hours or with sham procedure. Subsequently, serum and hippocampal tissues were harvested for analysis. Further investigation into the relationship between isatin and neuroinflammation was conducted using BV2 microglial cells.Results Sevoflurane anesthesia led to the activation of inflammatory pathways, an increased presence of hippocampal astrocytes and microglia, and elevated expression of neuroinflammatory cytokines. Comparative analysis identified 12 differential metabolites that exhibited changes in both human and mouse serum post-sevoflurane anesthesia. Notably, isatin levels were significantly decreased after anesthesia. Notably, isatin levels significantly decreased after anesthesia, a factor known to stimulate proliferation and proinflammatory gene expression in microglia—the pivotal cell type in inflammatory responses.Conclusion Sevoflurane-induced alterations in serum metabolites in both elderly patients and aging mice, subsequently contributing to increased inflammation in the hippocampus.
研究领域:
麻醉学
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神经科学
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老年医学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
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2023
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IF 6.1
Feng Zhang,Jia Xu,Yanzhou Hu,Jingjing Fang,Minglan Yang,Kunlun Huang,Wentao Xu,Xiaoyun He
Aging is a major cause of bone loss and osteoporosis. Diallyl trisulfide (DATS), one of the main organic sulfides in garlic oil, has been shown to alleviate arthritis in mice. However, further research is still needed to determine how DATS affects bone formation and bone loss in aging mice. Here, we established a mouse model of natural aging for dietary DATS intervention. DATS treatment improved bone microstructure, including the disorganized arrangement of bone trabeculae and promoted collagen synthesis, with micro-CT and histological analyses. The abundance of beneficial bacteria for bone formation, such as Clostridiaceae and Erysipelotorichaceae, as well as the microbial diversity and community richness, were all altered by DATS, according to 16S rRNA sequencing data. 14 potential biomarkers and 9 important metabolic pathways were examined using serum metabolomics analysis. Additionally, there has been a significant reduction in sphingosine, which was directly associated with bone metabolism. The level of sphingosine and relative abundance of Clostridium were found to be negatively correlated by correlation analysis, indicating that bacteria may regulate bone reconstruction via influencing metabolites. Furthermore, Runx2 and β-catenin gene expression levels increased in bone, which may be related to the ameliorative mechanism of DATS. Our results suggested that DATS may prevent age-related bone loss by upregulating osteogenic gene expression through altering gut microbes and serum metabolism.
研究领域:
老年学
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药理学
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微生物学
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代谢组学
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骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）