Dataset Information

Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na⁺/K⁺-ATPase Dysfunction in Vascular Dementia.

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.

SUBMITTER: Philbert SA

PROVIDER: S-EPMC8832097 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na<sup>+</sup>/K<sup>+</sup>-ATPase Dysfunction in Vascular Dementia.

Philbert Sasha A SA Xu Jingshu J Scholefield Melissa M Church Stephanie J SJ Unwin Richard D RD Cooper Garth J S GJS

Frontiers in aging neuroscience 20220128

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 ...[more]

PMID: 35153731

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Project description:Combined 23Na/39K MRI at 7 T can highlight ion disturbances in skeletal muscle tissue. In this work, we investigated if the apparent tissue potassium concentration (aTPC) can be determined in fatty replaced muscles of patients with facio-scapulo-humeral muscular dystrophy (FSHD) and if it can provide additional information to the fat replacement and the apparent tissue sodium concentration (aTSC). The lower leg of 14 patients (six females, eight males; mean age 47.7 ± 14.0 years) with genetically confirmed FSHD and 11 healthy controls (four females, seven males; mean age 47.0 ± 14.0 years) was examined at a 7-T MR system using a dual-tuned 23Na/39K birdcage RF coil. In addition, qualitative and quantitative 1H MR measurements were performed at 7 T to assess the fat replacement and water accumulation. The aTPC and aTSC were determined in seven different muscle regions based on five external references phantoms and corrected for partial volume effects, relaxation biases, and reduced ion concentrations in fat. Results are expressed as median (interquartile range). The measured aTPC was strongly reduced in fat-replaced muscles and was close to zero in totally fat replaced muscles (aTPC = 4.3 mM [2.7 mM] for FF > 80%). After correction of aTPC values for reduced potassium concentration in fat, aTPCfc values of patients in muscles with low or moderate fat fraction (FF < 30%) were similar to values of healthy subjects (patients: aTPCfc = 85.6 mM [21.7 mM]; controls: aTPCfc = 83.2 mM [22.3 mM]). However, muscles with FF > 30% showed reduced aTPCfc and increased aTSCfc compared with healthy controls (aTPCfc = 28.9 mM [46.2 mM], aTSCfc = 42.3 mM [17.6 mM]; controls: aTSCfc = 15.0 mM [4.6 mM], aTPCfc = 83.2 mM [22.3 mM]). No correlations were observed between the aTPCfc and aTSCfc, or between aTPCfc and water T2. We showed that a determination of the aTPC in dystrophic skeletal muscles is feasible using 39K MRI at 7 T. Measured changes in aTPCfc were greater than sole fat replacement and might therefore be used as an additional quantitative measure for dystrophic muscle tissue.

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Dataset Information

Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na⁺/K⁺-ATPase Dysfunction in Vascular Dementia.

Publications

Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na<sup>+</sup>/K<sup>+</sup>-ATPase Dysfunction in Vascular Dementia.

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Dataset Information

Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na+/K+-ATPase Dysfunction in Vascular Dementia.

Publications

Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na<sup>+</sup>/K<sup>+</sup>-ATPase Dysfunction in Vascular Dementia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na⁺/K⁺-ATPase Dysfunction in Vascular Dementia.