Related Experiment Video
Updated: Oct 3, 2025
Ex Vivo Pressurized Hippocampal Capillary-Parenchymal Arteriole Preparation for Functional Study
Published on: December 18, 2019
Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na+/K+-ATPase Dysfunction in
Sasha A Philbert1, Jingshu Xu1, Melissa Scholefield1
1Centre for Advanced Discovery and Experimental Therapeutics, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Insights
Vascular dementia (VaD) shows altered sodium and potassium levels in the hippocampus, suggesting potential diagnostic markers. Further research into metal dyshomeostasis may reveal new therapeutic targets for this common elderly dementia.
Area of Science:
- Neuroscience
- Metallomics
- Gerontology
Background:
- Vascular dementia (VaD) is a leading cause of dementia in the elderly.
- Current treatments for VaD lack disease-modifying capabilities.
- The role of metal dyshomeostasis in VaD pathogenesis is poorly understood.
Purpose of the Study:
- To investigate metal concentrations in the hippocampus of VaD patients.
- To compare the metallomic profile of VaD with other neurodegenerative diseases.
- To identify potential biomarkers for VaD.
Main Methods:
- Inductively coupled-plasma mass spectrometry (ICP-MS) was used to quantify nine essential metals.
- Post-mortem hippocampal tissue from VaD cases (n=10) and controls (n=10) was analyzed.
- Principal component analysis (PCA) was applied for comparative metallomic pattern analysis.
Main Results:
- Significantly elevated hippocampal sodium (Na) levels and Na/K ratios were observed in VaD.
- Decreased potassium (K) levels were noted in wet-weight tissue analysis.
- No distinct hippocampal metal-pattern differences were found between VaD and other studied neurodegenerative diseases.
Conclusions:
- Altered Na and K levels in VaD hippocampus may indicate Na+/K+-exchanging ATPase dysfunction.
- This dysfunction could be linked to impaired ATP generation.
- Cerebral sodium measurement shows potential as a diagnostic tool for VaD.
Abstract:
Vascular dementia (VaD) is thought to be the second most common cause of age-related dementia amongst the elderly. However, at present, there are no available disease-modifying therapies for VaD, probably due to insufficient understanding about the molecular basis of the disease. While the notion of metal dyshomeostasis in various age-related dementias has gained considerable attention in recent years, there remains little comparable investigation in VaD. To address this evident gap, we employed inductively coupled-plasma mass spectrometry to measure the concentrations of nine essential metals in both dry- and wet-weight hippocampal post-mortem tissue from cases with VaD (n = 10) and age-/sex-matched controls (n = 10). We also applied principal component analysis to compare the metallomic pattern of VaD in the hippocampus with our previous hippocampal metal datasets for Alzheimer's disease, Huntington's disease, Parkinson's disease, and type-2 diabetes, which had been measured using the same methodology. We found substantive novel evidence for elevated hippocampal Na levels and Na/K ratios in both wet- and dry-weight analyses, whereas decreased K levels were present only in wet tissue. Multivariate analysis revealed no distinguishable hippocampal differences in metal-evoked patterns between these dementia-causing diseases in this study. Contrasting levels of Na and K in hippocampal VaD tissue may suggest dysfunction of the Na+/K+-exchanging ATPase (EC 7.2.2.13), possibly stemming from deficient metabolic energy (ATP) generation. These findings therefore highlight the potential diagnostic importance of cerebral sodium measurement in VaD patients.
