TY - JOUR
T1 - Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na +/K +-ATPase Dysfunction in Vascular Dementia
AU - Philbert, Sasha
AU - Cooper, Garth JS
AU - Xu, Jingshu
AU - Unwin, Richard
AU - Church, Stephanie
AU - Scholefield, Melissa
N1 - Funding Information:
We would like to thank the South West Dementia Brain Bank (SWDBB) for providing brain tissue for this study. The SWDBB is part of the Brains for Dementia Research program, jointly funded by Alzheimer’s Research UK and Alzheimer’s Society and is supported by BRACE (Bristol Research into Alzheimer’s and Care of the Elderly) and the Medical Research Council.
Funding Information:
This work was supported by The Endocore Research Trust (NZ) (60187); the Lee Trust (NZ); the Oakley Mental Health Research Foundation (NZ) (3456030; 3627092; 3701339; 3703253; and 3702879); the Maurice and Phyllis Paykel Trust (3627036); the UKRI Medical Research Council (MR/N0284457/1); the NZ Ministry of Business, Innovation and Employment (PROP-57362-ENDRP-UOA; 3716382); The University of Manchester; the Northwest Regional Development Agency through a combined programme grant to CADET; and facilitated by the Greater Manchester Comprehensive Local Research Network.
Publisher Copyright:
Copyright © 2022 Philbert, Xu, Scholefield, Church, Unwin and Cooper.
PY - 2022/1/28
Y1 - 2022/1/28
N2 - 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.
AB - 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.
KW - Na /K -exchanging ATPase
KW - brain-potassium levels
KW - brain-sodium levels
KW - metal dyshomeostasis
KW - neurodegeneration
KW - vascular dementia
U2 - 10.3389/fnagi.2022.822787
DO - 10.3389/fnagi.2022.822787
M3 - Article
C2 - 35153731
VL - 14
SP - 822787
JO - Frontiers in aging neuroscience
JF - Frontiers in aging neuroscience
SN - 1663-4365
M1 - 822787
ER -