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Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy
- Source :
- Aging (Albany NY)
- Publication Year :
- 2021
- Publisher :
- Impact Journals, LLC, 2021.
-
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.
- Subjects :
- Male
Aging
Interleukin-1beta
uremic toxin
Anxiety
Gut flora
medicine.disease_cause
Nephrectomy
neuroinflammation
Neural Stem Cells
Neurotrophic factors
Behavior, Animal
biology
Depression
Neurodegeneration
neurodegeneration
Oxides
medicine.anatomical_structure
Injections, Intraperitoneal
Research Paper
Serotonin
medicine.medical_specialty
Cell Survival
Neurogenesis
Central nervous system
Prefrontal Cortex
Internal medicine
medicine
Animals
Cognitive Dysfunction
RNA, Messenger
Renal Insufficiency, Chronic
Neuroinflammation
gut microbiota
business.industry
Brain-Derived Neurotrophic Factor
Cell Biology
medicine.disease
Aryl hydrocarbon receptor
biology.organism_classification
Carbon
Mice, Inbred C57BL
Repressor Proteins
Affect
Oxidative Stress
Endocrinology
biology.protein
Corticosterone
business
Indican
Oxidative stress
Kidney disease
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....0ef3db6d40e42a2d3b101947664d7849