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X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology. 脑组织的 X 射线荧光绘图揭示了中风病理生理学中微量元素失调的严重程度。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-11-15 DOI: 10.1093/mtomcs/mfae054

M Jake Pushie, Nicole J Sylvain, Huishu Hou, Nicole Pendleton, Richard Wang, Liam Zimmermann, Maxwell Pally, Francisco S Cayabyab, Lissa Peeling, Michael E Kelly

{"title":"X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology.","authors":"M Jake Pushie, Nicole J Sylvain, Huishu Hou, Nicole Pendleton, Richard Wang, Liam Zimmermann, Maxwell Pally, Francisco S Cayabyab, Lissa Peeling, Michael E Kelly","doi":"10.1093/mtomcs/mfae054","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae054","url":null,"abstract":"The brain is a privileged organ with regards to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischemic changes begin almost immediately, triggering an ischemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and break down of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains < 25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and > 150%, respectively). We hypothesize that weakening of the blood-brain-barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The changes observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alterations in Zinc, Copper, and Iron Levels in the Retina and Brain of Alzheimer's Disease Patients and the APP/PS1 Mouse Model. 阿尔茨海默病患者视网膜和大脑以及 APP/PS1 小鼠模型中锌、铜和铁水平的变化。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-11-08 DOI: 10.1093/mtomcs/mfae053

Seyed Mostafa Hosseinpour Mashkani, David Bishop, Mika T Westerhausen, Paul A Adlard, S Mojtaba Golzan

{"title":"Alterations in Zinc, Copper, and Iron Levels in the Retina and Brain of Alzheimer's Disease Patients and the APP/PS1 Mouse Model.","authors":"Seyed Mostafa Hosseinpour Mashkani, David Bishop, Mika T Westerhausen, Paul A Adlard, S Mojtaba Golzan","doi":"10.1093/mtomcs/mfae053","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae053","url":null,"abstract":"Transition metals like copper, iron, and zinc are vital for normal central nervous system function and are also linked to neurodegeneration, particularly in the onset and progression of Alzheimer's disease (AD). Their alterations in AD, identified prior to amyloid plaque aggregation, offer a unique target for staging pre-amyloid AD. However, analysing their levels in the brain is extremely challenging, necessitating the development of alternative approaches. Here, we utilised laser ablation-inductively coupled plasma-mass spectrometry and solution nebulisation-inductively coupled plasma-mass spectrometry to quantitatively measure Cu, Fe, and Zn concentrations in the retina and hippocampus samples obtained from human donors (i.e., AD and healthy controls), and in the APP/PS1 mouse model of AD, and Wild Type controls, aged 9 and 18 months. Our findings revealed significantly elevated Cu, Fe, and Zn levels in the retina (*p < 0.05, **p < 0.01, ***p < 0.001) and hippocampus (*p < 0.05, *p < 0.05, *p < 0.05) of human AD samples compared to healthy controls. Conversely, APP/PS1 mouse models exhibited notably lower metal levels in the same regions compared to WT mice, Cu, Fe, and Zn levels in the retina (**p < 0.01, *p < 0.05, *p < 0.05) and hippocampus (**p < 0.01, **p < 0.01, *p < 0.05). The contrasting metal profiles in human and mouse samples, yet similar patterns within each species' retina and brain, suggest the retina mirrors cerebral metal dyshomeostasis in AD. Our findings lay the groundwork for staging pre-AD pathophysiology through assessment of transition metal levels in the retina.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0