Acute hypoxia induces sleep disorders via sima/HIF-1α regulation of circadian rhythms in adult Drosophila

Abstract

The atmospheric oxygen concentration is significantly reduced in highland regions compared to lowland areas. The first entering the plateau can induce sleep disorders in individuals, primarily attributed to insufficient oxygen supply. This study used Drosophila melanogaster as a model organism to better understand the molecular mechanism of acute hypoxia-induced sleep disorders. The Drosophila activity monitoring system (DAMS) was employed to observe the sleep-wake in adult (w¹¹¹⁸, sima^KG07607, and clock^jrk) female flies. Quantifying the relative mRNA expression levels of sima and circadian clock genes in the head of flies was accomplished by utilizing qRT-PCR. Acute hypoxia caused sleep disorders in w¹¹¹⁸ flies, such as shortened sleep duration and length, and prolonged sleep latency. PCR results showed that sima and clock genes were up-regulated in ZT6 and ZT12 and down-regulated in ZT0 and ZT18 in acute hypoxic w¹¹¹⁸ flies compared to normoxic w¹¹¹⁸ flies. Under normoxic conditions, sleep indexes in sima^KG07607 flies were not substantially different from w¹¹¹⁸ flies. However, clock^jrk flies demonstrated a reduced sleep duration, decreased sleep bout length, and increased sleep latency and activities. Sleep and gene expression in sima^KG07607 flies under acute hypoxic conditions were not significantly different from those under normoxic conditions. Surprisingly, sleep and gene expression in clock^jrk flies showed opposite trends to w¹¹¹⁸ flies. The present study indicates that acute hypoxia disrupt circadian rhythms through the activation of sima/HIF-1α, leading to the onset of sleep disorders, with Clock signaling potentially serving as a contributing factor.

Keywords: Acute hypoxia; Circadian rhythms; Drosophila; Sleep disorders; sima/HIF-1α.