Privação de sono em Drosophila melanogaster resulta em alterações na homeostase redox, mitocondrial e na expressão gênica de reguladores da função circadiana e metabólica

Abstract

Sleep deprivation and related diseases, such as metabolic disorders, are consequences of the busy lifestyle of modern society. Sleep is a crucial resting state for survival and regulated by circadian rhythms. Changes in these rhythms affect antioxidant defense systems, cause oxidative damage and metabolic deficiencies, but the mechanisms involved in these changes are still unclear. In this study we evaluated the effects of sleep deprivation on Drosophila melanogaster flies maintained in constant light. Exposure of flies to the continuous light condition was able to cause changes in sleep patterns, characterizing homeostatic sleep regulation. Sleep deprivation of flies by 24-hour light exposure caused decreased locomotor activity, increased GST, SOD, and TRxR enzymes, as well as decreased CAT activity. Increased levels of reactive oxygen species and lipid peroxidation, mitochondrial dysfunction, decreased glucose, triglycerides and glycogen levels and increased caspase 3/7 activity were also observed. In addition, sleep deprived flies showed alterations in the expression of genes involved in oxidative stress pathways, circadian control and metabolic regulation. The increase in gene expression of Nrf2, p38β, Pp2a, pale, Akt1, Clk, cyc, per, tim, cry, pdf and in the dilp2, 3 and 8 genes. On the other hand, the dbt and dilp4, 5, 6 and 7 genes showed a significant decrease in their expression. Taken together, our data suggest a close relationship between sleep deprivation, circadian control, oxidative stress, and metabolic regulation, indicating that sleep deprivation, even for a short period of time, is capable of causing deleterious effects on the body, and further enhances use of Drosophila melanogaster as a model organism for studies related to sleep and metabolism.