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KMID : 1151920230050020071
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Chronobiology in Medicine
2023 Volume.5 No. 2 p.71 ~ p.81
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Effect of Withanolide-A on Mice Subjected to Simulated Chronic Jetlag/Shift Work
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Trisha Tiwari
Madhumita Mishra
Muniyandi Singaravel
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Abstract
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Objective : Circadian rhythm is maintained by central and peripheral clocks that regulate an organism’s physiological functions. Frequent trans-meridian travel, an irregular sleep-wake cycle, light exposure during the rest period, rotating shift work, and other factors cause desynchronization of central and peripheral clocks, impairing social and occupational behavior. Withanolide-A (WA) is used for its powerful nootropic and neuroprotective properties.
Methods ; Effects of 13 days consecutive pre-dosing of WA (10 μmol/kg/day) on circadian rhythm disruption caused due to 9 h advance-delay chronic jetlag light-dark shift was studied on re-entrainment rate analyzed through locomotor activity recording of mice using the ClockLab setup, learning and memory studied through Y-maze and Barnes maze tests. In the hippocampus, gene expression of PER1 and BDNF was assessed using reverse transcription-quantitative polymerase chain reaction. The effect of WA treatment was also studied on superoxide dismutase, catalase, reactive oxygen species (ROS), and lipid peroxidation in hippocampal tissue.
Results : The results showed that WA treatment leads to faster re-entrainment and better performance during Y-maze and Barnes maze tests. PER1 and BDNF genes expression was upregulated in the treated group compared to chronic jetlag exposure groups in the hippocampus and suprachiasmatic nuclei. Moreover, the WA-treated group produced fewer ROS and superoxide radicals, and there was also less lipid peroxidation in the treated group.
Conclusion : These results suggest that the WA may act as a chronobiotic and neuroprotective agent as treated group mice took fewer transient cycles to re-entrain after chronic light-dark shift. Neuroprotective property is supported by learning-memory behavioral tests, gene studies and biochemical assays.
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KEYWORD
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Circadian rhythm, Withanolide-A, Chronic jetlag, Spatial memory
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