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Dietary Salt Disrupts Tricarboxylic Acid Cycle and Induces Tau Hyperphosphorylation and Synapse Dysfunction during Aging
Dietary salt causes synaptic deficits and tau hyperphosphorylation, which are detrimental to cognitive function. However, the specific effects of a high-salt diet on synapse and tau protein remain poorly understood. In this study, aged (15-month-old) C57BL/6 mice received a normal (0.5% NaCl) or hig...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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JKL International LLC
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9466974/ https://www.ncbi.nlm.nih.gov/pubmed/36186135 http://dx.doi.org/10.14336/AD.2022.0220 |
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author | Yuan, Minghao Wang, Yangyang Wen, Jie Jing, Feng Zou, Qian Pu, Yinshuang Pan, Tingyu Cai, Zhiyou |
author_facet | Yuan, Minghao Wang, Yangyang Wen, Jie Jing, Feng Zou, Qian Pu, Yinshuang Pan, Tingyu Cai, Zhiyou |
author_sort | Yuan, Minghao |
collection | PubMed |
description | Dietary salt causes synaptic deficits and tau hyperphosphorylation, which are detrimental to cognitive function. However, the specific effects of a high-salt diet on synapse and tau protein remain poorly understood. In this study, aged (15-month-old) C57BL/6 mice received a normal (0.5% NaCl) or high-salt (8% NaCl) diet for 3 months, and N2a cells were treated with normal culture medium or a NaCl medium (40 mM). Spatial learning and memory abilities were tested using the Morris water maze. The levels of metabolites and related enzymes in the tricarboxylic acid (TCA) cycle were confirmed using liquid chromatography-tandem mass spectrometry, western blotting, and immunofluorescence. We also investigated synapse morphology and the phosphorylation of tau protein. Under the high-salt diet, mice displayed impaired learning and memory compared to mice fed the normal diet. Furthermore, excessive salt intake disturbed the TCA cycle in both animals and cells compared to the respective normal controls. High dietary salt reduced postsynaptic density protein 95 (PSD95) and brain-derived neurotrophic factor (BDNF) expression, impaired neurons, and caused synaptic loss in the mice. We also detected tau hyperphosphorylation at different sites (Thr205, Thr231, and Thr181) without increasing total tau levels in response to high salt treatment, both in vivo and in vitro. We concluded that elevated salt intake impairs the TCA cycle and induces tau hyperphosphorylation and synapse dysfunction during aging, which ultimately results in cognitive impairment. |
format | Online Article Text |
id | pubmed-9466974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | JKL International LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-94669742022-10-01 Dietary Salt Disrupts Tricarboxylic Acid Cycle and Induces Tau Hyperphosphorylation and Synapse Dysfunction during Aging Yuan, Minghao Wang, Yangyang Wen, Jie Jing, Feng Zou, Qian Pu, Yinshuang Pan, Tingyu Cai, Zhiyou Aging Dis Original Article Dietary salt causes synaptic deficits and tau hyperphosphorylation, which are detrimental to cognitive function. However, the specific effects of a high-salt diet on synapse and tau protein remain poorly understood. In this study, aged (15-month-old) C57BL/6 mice received a normal (0.5% NaCl) or high-salt (8% NaCl) diet for 3 months, and N2a cells were treated with normal culture medium or a NaCl medium (40 mM). Spatial learning and memory abilities were tested using the Morris water maze. The levels of metabolites and related enzymes in the tricarboxylic acid (TCA) cycle were confirmed using liquid chromatography-tandem mass spectrometry, western blotting, and immunofluorescence. We also investigated synapse morphology and the phosphorylation of tau protein. Under the high-salt diet, mice displayed impaired learning and memory compared to mice fed the normal diet. Furthermore, excessive salt intake disturbed the TCA cycle in both animals and cells compared to the respective normal controls. High dietary salt reduced postsynaptic density protein 95 (PSD95) and brain-derived neurotrophic factor (BDNF) expression, impaired neurons, and caused synaptic loss in the mice. We also detected tau hyperphosphorylation at different sites (Thr205, Thr231, and Thr181) without increasing total tau levels in response to high salt treatment, both in vivo and in vitro. We concluded that elevated salt intake impairs the TCA cycle and induces tau hyperphosphorylation and synapse dysfunction during aging, which ultimately results in cognitive impairment. JKL International LLC 2022-10-01 /pmc/articles/PMC9466974/ /pubmed/36186135 http://dx.doi.org/10.14336/AD.2022.0220 Text en copyright: © 2022 Yuan et al. https://creativecommons.org/licenses/by/2.0/this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Original Article Yuan, Minghao Wang, Yangyang Wen, Jie Jing, Feng Zou, Qian Pu, Yinshuang Pan, Tingyu Cai, Zhiyou Dietary Salt Disrupts Tricarboxylic Acid Cycle and Induces Tau Hyperphosphorylation and Synapse Dysfunction during Aging |
title | Dietary Salt Disrupts Tricarboxylic Acid Cycle and Induces Tau Hyperphosphorylation and Synapse Dysfunction during Aging |
title_full | Dietary Salt Disrupts Tricarboxylic Acid Cycle and Induces Tau Hyperphosphorylation and Synapse Dysfunction during Aging |
title_fullStr | Dietary Salt Disrupts Tricarboxylic Acid Cycle and Induces Tau Hyperphosphorylation and Synapse Dysfunction during Aging |
title_full_unstemmed | Dietary Salt Disrupts Tricarboxylic Acid Cycle and Induces Tau Hyperphosphorylation and Synapse Dysfunction during Aging |
title_short | Dietary Salt Disrupts Tricarboxylic Acid Cycle and Induces Tau Hyperphosphorylation and Synapse Dysfunction during Aging |
title_sort | dietary salt disrupts tricarboxylic acid cycle and induces tau hyperphosphorylation and synapse dysfunction during aging |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9466974/ https://www.ncbi.nlm.nih.gov/pubmed/36186135 http://dx.doi.org/10.14336/AD.2022.0220 |
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