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Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy
Chronic Kidney Disease (CKD) and neurodegenerative diseases are aging-related diseases. CKD with declined renal function is associated with an elevation of circulating indoxyl sulfate, a metabolite synthesized by gut microbes. We explored the roles of gut microbial metabolites in linking with Centra...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993681/ https://www.ncbi.nlm.nih.gov/pubmed/33621199 http://dx.doi.org/10.18632/aging.202523 |
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author | Sun, Chiao-Yin Li, Jian-Ri Wang, Ya-Yu Lin, Shih-Yi Ou, Yen-Chuan Lin, Cheng-Jui Wang, Jiaan-Der Liao, Su-Lan Chen, Chun-Jung |
author_facet | Sun, Chiao-Yin Li, Jian-Ri Wang, Ya-Yu Lin, Shih-Yi Ou, Yen-Chuan Lin, Cheng-Jui Wang, Jiaan-Der Liao, Su-Lan Chen, Chun-Jung |
author_sort | Sun, Chiao-Yin |
collection | PubMed |
description | Chronic Kidney Disease (CKD) and neurodegenerative diseases are aging-related diseases. CKD with declined renal function is associated with an elevation of circulating indoxyl sulfate, a metabolite synthesized by gut microbes. We explored the roles of gut microbial metabolites in linking with Central Nervous System (CNS) diseases by administrating indoxyl sulfate intraperitoneally to male C57BL/6 mice with unilateral nephrectomy. Upon exposure, the accumulation of indoxyl sulfate was noted in the blood, prefrontal cortical tissues, and cerebrospinal fluid. Mice showed behavioral signs of mood disorders and neurodegeneration such as anxiety, depression, and cognitive impairment. Those behavioral changes were accompanied by disturbed neuronal survival, neural stem cell activity, expression of Brain-Derived Neurotrophic Factor, serotonin, corticosterone, and Repressor Element-1 Silencing Transcription Factor, and post-receptor intracellular signaling, as well as upregulated oxidative stress and neuroinflammation. Uremic toxin adsorbent AST-120 improved the above mentioned changes. Intriguingly, intracerebroventricular indoxyl sulfate administration only caused limited alterations in the normal mice and the alterations were reversed by aryl hydrocarbon receptor antagonism. The findings suggest pathogenic roles of indoxyl sulfate in the development of CNS diseases, and highlight gut microbiota as alternative targets for intervention with the aim of slowing down the progression of CKD and decreasing CNS complications. |
format | Online Article Text |
id | pubmed-7993681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-79936812021-04-06 Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy Sun, Chiao-Yin Li, Jian-Ri Wang, Ya-Yu Lin, Shih-Yi Ou, Yen-Chuan Lin, Cheng-Jui Wang, Jiaan-Der Liao, Su-Lan Chen, Chun-Jung Aging (Albany NY) Research Paper Chronic Kidney Disease (CKD) and neurodegenerative diseases are aging-related diseases. CKD with declined renal function is associated with an elevation of circulating indoxyl sulfate, a metabolite synthesized by gut microbes. We explored the roles of gut microbial metabolites in linking with Central Nervous System (CNS) diseases by administrating indoxyl sulfate intraperitoneally to male C57BL/6 mice with unilateral nephrectomy. Upon exposure, the accumulation of indoxyl sulfate was noted in the blood, prefrontal cortical tissues, and cerebrospinal fluid. Mice showed behavioral signs of mood disorders and neurodegeneration such as anxiety, depression, and cognitive impairment. Those behavioral changes were accompanied by disturbed neuronal survival, neural stem cell activity, expression of Brain-Derived Neurotrophic Factor, serotonin, corticosterone, and Repressor Element-1 Silencing Transcription Factor, and post-receptor intracellular signaling, as well as upregulated oxidative stress and neuroinflammation. Uremic toxin adsorbent AST-120 improved the above mentioned changes. Intriguingly, intracerebroventricular indoxyl sulfate administration only caused limited alterations in the normal mice and the alterations were reversed by aryl hydrocarbon receptor antagonism. The findings suggest pathogenic roles of indoxyl sulfate in the development of CNS diseases, and highlight gut microbiota as alternative targets for intervention with the aim of slowing down the progression of CKD and decreasing CNS complications. Impact Journals 2021-02-17 /pmc/articles/PMC7993681/ /pubmed/33621199 http://dx.doi.org/10.18632/aging.202523 Text en Copyright: © 2021 Sun et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Sun, Chiao-Yin Li, Jian-Ri Wang, Ya-Yu Lin, Shih-Yi Ou, Yen-Chuan Lin, Cheng-Jui Wang, Jiaan-Der Liao, Su-Lan Chen, Chun-Jung Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy |
title | Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy |
title_full | Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy |
title_fullStr | Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy |
title_full_unstemmed | Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy |
title_short | Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy |
title_sort | indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993681/ https://www.ncbi.nlm.nih.gov/pubmed/33621199 http://dx.doi.org/10.18632/aging.202523 |
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