Abstract: FR-PO1019
Gut-Derived Uremic Toxins Correlate with Anxiety and Decreased Locomotor Activity in CKD Mice
Session Information
- CKD Mechanisms: From Mendel to Mars
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Zhao, Yitong, University of California Irvine, Irvine, California, United States
- Liu, Han, University of California Irvine, Irvine, California, United States
- Jung, Joshua J., University of California Irvine, Irvine, California, United States
- Vancheeswaran, Nikitha M., University of California Irvine, Irvine, California, United States
- Tran-Phung, Lily, University of California Irvine, Irvine, California, United States
- Lau, Wei Ling, University of California Irvine, Irvine, California, United States
Background
The altered gut microbiome in chronic kidney disease (CKD) is a source of circulating uremic toxins including p-cresyl sulfate (pCS), indoxyl sulfate (IS), and trimethylamine N-oxide (TMAO). Microbe-derived uremic toxins have been correlated with depression and cognitive impairment in CKD patients. In the current study, continuous subcutaneous infusion of gut-derived toxins was done to evaluate the impact of gut-derived uremic toxins on behavior outcomes in CKD mice.
Methods
Male and female C57Bl/6J mice were randomly assigned to control or CKD groups. Tubulointerstitial nephritis CKD was induced by 0.2% adenine diet. Alzet pumps containing placebo (PBS) or uremic toxins (a mix of pCS, IS and TMAO) were implanted which delivered continuous subcutaneous dosing for 4 weeks. Prior to termination, spontaneous locomotion and anxiety (open field test) and recognition memory (novel object recognition test) were assessed. Serum levels of creatinine and gut-derived uremic toxins were measured. Group means were compared using ANOVA, and correlation analyses were done using Spearman’s coefficient (r).
Results
Serum creatinine, pCS, IS, and TMAO were significantly elevated in CKD vs control mice (Table). Toxin infusion in CKD animals (CKD/Toxins) further increased serum pCS and IS compared to CKD/PBS mice in both sexes. Male and female CKD animals demonstrated decreased exploratory behavior (increased anxiety). Higher levels of creatinine, IS and TMAO were significantly associated with anxiety behavior. Infusion of gut-derived toxins did not further increase anxiety behavior compared to PBS (Figure). Recognition memory was not altered in CKD mice.
Conclusion
Gut-derived uremic toxins were significantly correlated with anxiety behavior in CKD mice. However, infusion of toxins did not further worsen behavior scores beyond control vs CKD status.
Funding
- Other NIH Support