ArticleAging2021
Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy.
Article in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Indoxyl Sulfate and Autism Spectrum Disorder: A Literature Review.International journal of molecular sciences · 2024Pooled it
- Strain-resolved metabolomic chemotyping identifies tryptophan and γ-glutamyl peptides as MGO-AGEs breaking postbiotic compounds for carbonyl stress mitigation.Gut microbes · 2026Article
- Depression in chronic kidney disease and dialysis: A psychonephrology narrative review.World journal of nephrology · 2026Review
- Kaempferol conjugated selenium nanoparticles mitigate kidney injury from rhabdomyolysis through antioxidant and anti-inflammatory actions via Nrf2/NF-κb pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- The Kidney-Brain Axis in Chronic Kidney Disease: Uremic Toxins, Cognitive Decline, Mechanistic Pathways, Biomarkers and Therapeutic Perspectives.Biomedicines · 2026Review
- Investigating the Kidney-Gut-Brain Axis in CKD: Uremic Toxins and Brain Microhemorrhages.International journal of molecular sciences · 2026Article
- Depressive symptoms in chronic kidney disease: the hidden role of uremic toxins.BMJ mental health · 2026Article
- The Role of Diet and Gut Microbiome in CKD Progression and Therapy.Journal of clinical medicine · 2026Review
- Serum metabolomics identifies gut-derived uremic toxins and bile acid dysregulation associated with chronic kidney disease severity.Scientific reports · 2026Article
- The Role of Brain Structure in Explaining Physical Functioning in Male Veterans With Impaired Kidney Function.Journal of the American Geriatrics Society · 2026Article
- Research advances on the gut-kidney axis theory in sepsis-associated acute kidney injury.Frontiers in pharmacology · 2026Review
- Brain-derived extracellular vesicles circUsp32 polarized macrophages causing acute kidney injury after traumatic brain injury.Science advances · 2025Article
- Metabolomics and metagenomics in mice reveal the role of the gut microbiota in tryptophan metabolism.iScience · 2025Article
- Severity of atopic dermatitis is associated with gut-derived metabolites and leaky gut-related biomarkers.Scientific reports · 2025Article
- Uremic Toxins, CKD, and Cognitive Dysfunction.Journal of the American Society of Nephrology : JASN · 2025Review
- Select microbial metabolites in the small intestinal lumen regulate vagal activity via receptor-mediated signaling.iScience · 2025Article
- Indoxyl sulfate is associated with cognitive impairment in ESRD patients by activating the extrinsic apoptosis in the neuronal cells during differentiating process.International journal of medical sciences · 2025Article
- Research progress on the interaction between multiple organ-brain axes and perioperative neurocognitive disorders: a narrative review.Frontiers in aging neuroscience · 2025Review
- Development and validation of a comprehensive machine learning framework for a diagnostic model of uremia based on genes involved in major depressive disorder.Frontiers in nephrology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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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.