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- Title
Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na<sup>+</sup>/K<sup>+</sup>-ATPase Dysfunction in Vascular Dementia.
- Authors
Philbert, Sasha A.; Xu, Jingshu; Scholefield, Melissa; Church, Stephanie J.; Unwin, Richard D.; Cooper, Garth J. S.
- 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.
- Subjects
VASCULAR dementia; HUNTINGTON disease; ALZHEIMER'S disease; HIPPOCAMPUS (Brain); PARKINSON'S disease; PRINCIPAL components analysis; SODIUM metabolism; POTASSIUM metabolism; CONFIDENCE intervals; SODIUM; MULTIVARIATE analysis; POTASSIUM; MANN Whitney U Test; ADENOSINE triphosphatase; NEUROPSYCHOLOGICAL tests; MASS spectrometry; FACTOR analysis; DESCRIPTIVE statistics; RESEARCH funding; DATA analysis software
- Publication
Frontiers in Aging Neuroscience, 2022, Vol 14, p1
- ISSN
1663-4365
- Publication type
Article
- DOI
10.3389/fnagi.2022.822787