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Polygraphic Recording Procedure for Measuring Sleep in Mice
Published on: January 25, 2016
Exogenous Melatonin Attenuates Sleep Restriction-Induced Kidney Injury via Gut Microbiota-Derived Propionate in Mice
An Cui1, Qingyun Guan1, Zixu Wang1
1National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China.
Abstract:
Chronic sleep restriction (SR) impairs multiple organs. Although exogenous melatonin counteracts SR-induced gut microbiota disruption, its role in protecting renal function and the involvement of gut microbiota remain unclear. To this end, we subjected mice to a 28-day SR paradigm with exogenous melatonin treatment or antibiotic-induced microbiota depletion. SR mice demonstrated significant renal dysfunction evidenced by elevated serum creatinine, blood urea nitrogen, and uric acid levels compared to controls. Histopathological analysis revealed characteristic tubular abnormalities in SR mice, including epithelial degeneration and lumen dilation, with reduced expression of key renal filtration markers (Nephrin, Podocin, CD2-associated protein, and α-Actinin-4). All of these could be mitigated by melatonin treatment, and all changes were statistically significant (p < 0.05 or p < 0.01). Intriguingly, microbiota depletion significantly reversed the protective effect of exogenous melatonin on kidney injury in SR mice, while propionic acid supplementation mitigated SR-induced kidney injury. Furthermore, we found that gut microbiota and the metabolite propionic acid mediated the role of exogenous melatonin probably through attenuating SR-induced renal oxidative damage, including regulating renal superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) level. These findings collectively indicated that melatonin may ameliorate SR-associated kidney injury through gut microbiota-derived propionic acid. Our finding highlights a novel gut-kidney axis in SR-related pathophysiology.
Insights
Chronic sleep restriction harms kidneys. Melatonin protects kidney function by influencing gut microbiota and propionic acid, highlighting a new gut-kidney axis.
Area of Science:
- Nephrology
- Microbiology
- Endocrinology
Background:
- Chronic sleep restriction (SR) negatively impacts organ function, including the kidneys.
- Melatonin is known to affect gut microbiota, but its protective role in kidney function under SR is not well understood.
Purpose of the Study:
- To investigate the protective effect of exogenous melatonin on kidney function during chronic sleep restriction.
- To explore the role of gut microbiota and its metabolites in mediating melatonin's effects on kidney injury.
Main Methods:
- Mice underwent a 28-day sleep restriction paradigm.
- Treatments included exogenous melatonin, antibiotic-induced microbiota depletion, and propionic acid supplementation.
- Kidney function was assessed via serum markers, histopathology, and renal oxidative stress indicators.
Main Results:
- Sleep restriction induced significant renal dysfunction and tubular damage, with reduced filtration markers.
- Melatonin treatment mitigated these SR-induced kidney injuries.
- Microbiota depletion reversed melatonin's protective effects, while propionic acid supplementation ameliorated kidney injury.
Conclusions:
- Exogenous melatonin ameliorates sleep restriction-associated kidney injury.
- Gut microbiota, particularly propionic acid, mediates melatonin's protective effects by reducing renal oxidative damage.
- A novel gut-kidney axis is implicated in sleep restriction pathophysiology.
