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锰对神经元功能的影响：意大利布雷西亚铁合金工人的探索性多组学研究

Impact of Manganese on Neuronal Function: An Exploratory Multi-Omics Study on Ferroalloy Workers in Brescia, Italy.

作者信息

Azmoun Somaiyeh, Lewis Freeman C, Shoieb Daniel, Jin Yan, Colicino Elena, Mhatre-Winters Isha, Gu Haiwei, Krishnamurthy Hari, Richardson Jason R, Placidi Donatella, Lambertini Luca, Lucchini Roberto G

机构信息

Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA.

Department of Medical and Surgical Specialties, University of Brescia, 25123 Brescia, Italy.

出版信息

Brain Sci. 2025 Jul 31;15(8):829. doi: 10.3390/brainsci15080829.

DOI:10.3390/brainsci15080829
PMID:40867161
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12384076/
Abstract

BACKGROUND

There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer's Disease and related dementias (ADRD).

METHODS

In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals ( < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 µg/m (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls).

RESULTS

LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences ( < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25-35), GFAP, serotonin, NOVA1, and Siglec-1/CD169.

CONCLUSION

These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline.

摘要

背景

锰（Mn）在阿尔茨海默病及相关痴呆症（ADRD）发展中的潜在作用受到越来越多的关注。

方法

在这项针对铁合金工人队列的嵌套式试点研究中，我们通过β-淀粉样蛋白（Aβ）沉积和多组学分析，研究了慢性职业性锰暴露对认知功能的影响。我们评估了6名锰暴露男性工人（中位年龄63岁，暴露时长31年）和5名历史对照者（中位年龄60岁），他们均接受了脑部PET扫描。暴露个体的Aβ沉积显著更高（<0.05）。平均每年累积可吸入锰为329.23±516.39µg/m³（几何均值118.59），与对照组相比，暴露组的血浆锰水平显著升高（暴露组为0.704±0.2 ng/mL，对照组为0.397±0.18）。

结果

基于液相色谱-串联质谱的通路分析显示嗅觉信号、线粒体脂肪酸β-氧化、生物胺合成、跨膜转运和胆碱代谢受到干扰。单分子阵列免疫检测分析显示ADRD相关血浆生物标志物有显著改变。蛋白质微阵列显示靶向神经元和自身免疫蛋白的抗体存在显著差异（<0.05），包括Aβ（25-35）、胶质纤维酸性蛋白、血清素、NOVA1和唾液酸结合凝集素-1/CD169。

结论

这些发现表明锰暴露与神经退行性生物标志物改变以及与认知衰退相关的生物通路紊乱有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/15fe94dbafa9/brainsci-15-00829-g015.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/5f93f7d7c71c/brainsci-15-00829-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/90aa7b22fc46/brainsci-15-00829-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/bd8fc04cd654/brainsci-15-00829-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/3790820587a9/brainsci-15-00829-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/642e585c97f3/brainsci-15-00829-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/1133544e27bb/brainsci-15-00829-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/714d97025306/brainsci-15-00829-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/122a782ba809/brainsci-15-00829-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/bec51eceba2e/brainsci-15-00829-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/bd697db8bc9a/brainsci-15-00829-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/bb569b5ce5a0/brainsci-15-00829-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/d1d2e44760e2/brainsci-15-00829-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/0f3e907a722b/brainsci-15-00829-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/d4c81e45b5a6/brainsci-15-00829-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3713/12384076/15fe94dbafa9/brainsci-15-00829-g015.jpg

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