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Higher Circulating Trimethylamine N-Oxide Aggravates Cognitive Impairment Probably via Downregulating Hippocampal SIRT1 in Vascular Dementia Rats
Oxidative stress and inflammation damage play pivotal roles in vascular dementia (VaD). Trimethylamine N-oxide (TMAO), an intestinal microbiota-stemming metabolite, was reported to promote inflammation and oxidative stress, involved in the etiology of several diseases. Still, these effects have not...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688447/ https://www.ncbi.nlm.nih.gov/pubmed/36429082 http://dx.doi.org/10.3390/cells11223650 |
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author | Deng, Yang Zou, Junqing Hong, Ye Peng, Qiang Fu, Xinxin Duan, Rui Chen, Jie Chen, Xiangliang |
author_facet | Deng, Yang Zou, Junqing Hong, Ye Peng, Qiang Fu, Xinxin Duan, Rui Chen, Jie Chen, Xiangliang |
author_sort | Deng, Yang |
collection | PubMed |
description | Oxidative stress and inflammation damage play pivotal roles in vascular dementia (VaD). Trimethylamine N-oxide (TMAO), an intestinal microbiota-stemming metabolite, was reported to promote inflammation and oxidative stress, involved in the etiology of several diseases. Still, these effects have not been investigated in VaD. Here, we tested whether pre-existing, circulating, high levels of TMAO could affect VaD-induced cognitive decline. TMAO (120 mg/kg) was given to rats for a total of 8 weeks, and these rats underwent a sham operation or bilateral common carotid artery (2VO) surgery after 4 weeks of treatment. Four weeks after surgery, the 2VO rats exhibited hippocampal-dependent cognitive function declines and synaptic plasticity dysfunction, accompanied by an increase in oxidative stress, neuroinflammation, and apoptosis. TMAO administration, which increased plasma and hippocampal TMAO at 4 weeks postoperatively, further aggravated these effects, resulting in exaggerated cognitive and synaptic plasticity impairment, though not within the Sham group. Moreover, TMAO treatment activated the NLRP3 inflammasome and decreased SIRT1 protein expression within the hippocampus. However, these effects of TMAO were significantly attenuated by the overexpression of SIRT1. Our findings suggest that TMAO increases oxidative stress-induced neuroinflammation and apoptosis by inhibiting the SIRT1 pathway, thereby exacerbating cognitive dysfunction and neuropathological changes in VaD rats. |
format | Online Article Text |
id | pubmed-9688447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96884472022-11-25 Higher Circulating Trimethylamine N-Oxide Aggravates Cognitive Impairment Probably via Downregulating Hippocampal SIRT1 in Vascular Dementia Rats Deng, Yang Zou, Junqing Hong, Ye Peng, Qiang Fu, Xinxin Duan, Rui Chen, Jie Chen, Xiangliang Cells Article Oxidative stress and inflammation damage play pivotal roles in vascular dementia (VaD). Trimethylamine N-oxide (TMAO), an intestinal microbiota-stemming metabolite, was reported to promote inflammation and oxidative stress, involved in the etiology of several diseases. Still, these effects have not been investigated in VaD. Here, we tested whether pre-existing, circulating, high levels of TMAO could affect VaD-induced cognitive decline. TMAO (120 mg/kg) was given to rats for a total of 8 weeks, and these rats underwent a sham operation or bilateral common carotid artery (2VO) surgery after 4 weeks of treatment. Four weeks after surgery, the 2VO rats exhibited hippocampal-dependent cognitive function declines and synaptic plasticity dysfunction, accompanied by an increase in oxidative stress, neuroinflammation, and apoptosis. TMAO administration, which increased plasma and hippocampal TMAO at 4 weeks postoperatively, further aggravated these effects, resulting in exaggerated cognitive and synaptic plasticity impairment, though not within the Sham group. Moreover, TMAO treatment activated the NLRP3 inflammasome and decreased SIRT1 protein expression within the hippocampus. However, these effects of TMAO were significantly attenuated by the overexpression of SIRT1. Our findings suggest that TMAO increases oxidative stress-induced neuroinflammation and apoptosis by inhibiting the SIRT1 pathway, thereby exacerbating cognitive dysfunction and neuropathological changes in VaD rats. MDPI 2022-11-17 /pmc/articles/PMC9688447/ /pubmed/36429082 http://dx.doi.org/10.3390/cells11223650 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Deng, Yang Zou, Junqing Hong, Ye Peng, Qiang Fu, Xinxin Duan, Rui Chen, Jie Chen, Xiangliang Higher Circulating Trimethylamine N-Oxide Aggravates Cognitive Impairment Probably via Downregulating Hippocampal SIRT1 in Vascular Dementia Rats |
title | Higher Circulating Trimethylamine N-Oxide Aggravates Cognitive Impairment Probably via Downregulating Hippocampal SIRT1 in Vascular Dementia Rats |
title_full | Higher Circulating Trimethylamine N-Oxide Aggravates Cognitive Impairment Probably via Downregulating Hippocampal SIRT1 in Vascular Dementia Rats |
title_fullStr | Higher Circulating Trimethylamine N-Oxide Aggravates Cognitive Impairment Probably via Downregulating Hippocampal SIRT1 in Vascular Dementia Rats |
title_full_unstemmed | Higher Circulating Trimethylamine N-Oxide Aggravates Cognitive Impairment Probably via Downregulating Hippocampal SIRT1 in Vascular Dementia Rats |
title_short | Higher Circulating Trimethylamine N-Oxide Aggravates Cognitive Impairment Probably via Downregulating Hippocampal SIRT1 in Vascular Dementia Rats |
title_sort | higher circulating trimethylamine n-oxide aggravates cognitive impairment probably via downregulating hippocampal sirt1 in vascular dementia rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688447/ https://www.ncbi.nlm.nih.gov/pubmed/36429082 http://dx.doi.org/10.3390/cells11223650 |
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