ArticleNeurochemical research2019
Higher Circulating Trimethylamine N-oxide Sensitizes Sevoflurane-Induced Cognitive Dysfunction in Aged Rats Probably by Downregulating Hippocampal Methionine Sulfoxide Reductase A.
Article in Neurochemical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- The microbiota-gut- hippocampus axis.Frontiers in neuroscience · 2022Pooled it
- [Mechanisms of gutZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Dysbiosis and the gut-brain axis impairment in the pathophysiology of Alzheimer's disease and related dementias: is 'pathobiome' an etiological element?Essays in biochemistry · 2025Review
- The effect of TMAO on aging-associated cardiovascular and metabolic pathways and emerging therapies.Molecular and cellular biochemistry · 2025Review
- Trimethylamine N-Oxide Mitigates Perioperative Neurocognitive Disorders via ANXA1 Nuclear Translocation and M2 Microglial Polarization in the Hippocampus.CNS neuroscience & therapeutics · 2025Article
- The role of gut microbiota-derived metabolites in neuroinflammation.Neuroprotection (Chichester, England) · 2025Review
- The Role of Gut Microbiota-Derived Trimethylamine N-Oxide in the Pathogenesis and Treatment of Mild Cognitive Impairment.International journal of molecular sciences · 2025Review
- Exploring Mechanism of Electroacupuncture in Modulating Neuroinflammation Based on Intestinal Flora and Its Metabolites.Chinese journal of integrative medicine · 2025Review
- Decoding TMAO in the Gut-Organ Axis: From Biomarkers and Cell Death Mechanisms to Therapeutic Horizons.Drug design, development and therapy · 2025Review
- Interaction between gut microbiota and anesthesia: mechanism exploration and translation challenges focusing on the gut-brain-liver axis.Frontiers in cellular and infection microbiology · 2025Review
- Dysregulation of the Gut Microbiota Contributes to Sevoflurane-Induced Cognitive Dysfunction in Aged Mice by Activating the NLRP3 Inflammasome.Molecular neurobiology · 2024Article
- Orally Induced High Serum Level of Trimethylamine N-oxide Worsened Glial Reaction and Neuroinflammation on MPTP-Induced Acute Parkinson's Disease Model Mice.Molecular neurobiology · 2023Article
- Trimethylamine N-Oxide Exacerbates Neuroinflammation and Motor Dysfunction in an Acute MPTP Mice Model of Parkinson's Disease.Brain sciences · 2023Article
- Comorbidity of Anxiety and Hypertension: Common Risk Factors and Potential Mechanisms.International journal of hypertension · 2023Review
- Comparing the metabolic pathways of different clinical phases of bipolar disorder through metabolomics studies.Frontiers in psychiatry · 2023Article
- Association Between Metabolic Syndrome and Decline in Cognitive Function: A Cross-Sectional Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- The Wistar Kyoto Rat: A Model of Depression Traits.Current neuropharmacology · 2023Article
- Article
- Association of Trimethylamine N-Oxide with Normal Aging and Neurocognitive Disorders: A Narrative Review.Brain sciences · 2022Review
- Probiotics: Protecting Our Health from the Gut.Microorganisms · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) has recently been shown to promote oxidative stress and inflammation in the peripheral tissues, contributing to the pathogenesis of many diseases. Here we examined whether pre-existing higher circulating TMAO would influence cognitive function in aged rats after anesthetic sevoflurane exposure. Aged rats received vehicle or TMAO treatment for 3 weeks. After 2 weeks of treatment, these animals were exposed to either control or 2.6% sevoflurane for 4 h. One week after exposure, freezing as measured by fear conditioning test, microglia activity, proinflammatory cytokine expression and NADPH oxidase-dependent reactive oxygen species (ROS) production in the hippocampus (a key brain structure involved in learning and memory) were comparable between vehicle-treated rats exposed to control and vehicle-treated rats exposed to sevoflurane. TMAO treatment, which increased plasma TMAO before and 1 week after control or sevoflurane exposure, significantly reduced freezing to contextual fear conditioning, which was associated with increases in microglia activity, proinflammatory cytokine expression and NADPH oxidase-dependent ROS production in the hippocampus in rats exposed to sevoflurane but not in rats exposed to control. Moreover, hippocampal expression of antioxidant enzyme methionine sulfoxide reductase A (MsrA) was reduced by TMAO treatment in both groups, and TMAO-induced reduction in MsrA expression was negatively correlated with increased proinflammatory cytokine expression in rats exposed to SEV. These findings suggest that pre-existing higher circulating TMAO downregulates antioxidant enzyme MsrA in the hippocampus, which may sensitize the hippocampus to oxidative stress, resulting in microglia-mediated neuroinflammation and cognitive impairment in aged rats after sevoflurane exposure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.