Bhattacharya Debarati, Abaquita Terence L Al, Górska-Andrzejak Jolanta, Pyza Elzbieta
Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University Krakow, Kraków, Poland.
Dev Neurobiol. 2025 Jul;85(3):e22987. doi: 10.1002/dneu.22987.
Caffeine, a plant-derived psychostimulant, has been demonstrated to reduce sleep and increase dopaminergic neuron activity in mammals through competitive antagonism at adenosine receptors (AdoRs). However, the extent to which it influences daytime sleep (siesta) as much as nighttime sleep and the involvement of the adenosine signaling pathway in this process remain unsolved. It is similarly unclear whether the influence of caffeine varies with age and depends on sex and what type of cells it affects most; the clock cells that are involved in sleep timing and regulation or dopaminergic neurons, which are crucial for voluntary movement. To address this question, the role of caffeine has been investigated in Drosophila melanogaster (wild-type Canton-S flies), which has also been observed to reduce sleep in response to caffeine. The siesta and nighttime sleep of 3-, 30-, and 50-day-old males and females of Canton-S Drosophila were examined. Furthermore, transgenic flies with overexpressed or silenced dAdoR in all neurons (elav-expressing cells), the circadian clock cells (tim-expressing cells), and dopaminergic neurons (th-expressing cells) were studied. We found that females exhibited greater sensitivity to caffeine than males, and that older flies slept longer during the day than young flies. However, caffeine treatment resulted in reducing siesta in flies with overexpression of dAdoR in all neurons, tim-, and th-expressing cells. Conversely, silencing of dAdoR increased siesta. Therefore, the observed differences in the daytime sleep of Drosophila appeared to depend on signaling through AdoRs.
咖啡因是一种源自植物的精神兴奋剂，已被证明可通过对腺苷受体（AdoRs）的竞争性拮抗作用来减少哺乳动物的睡眠并增加多巴胺能神经元的活性。然而，它对白天睡眠（午睡）和夜间睡眠的影响程度，以及腺苷信号通路在此过程中的参与情况仍未得到解决。同样不清楚的是，咖啡因的影响是否随年龄而变化，是否取决于性别，以及它对哪种类型的细胞影响最大；是参与睡眠定时和调节的时钟细胞，还是对自主运动至关重要的多巴胺能神经元。为了解决这个问题，研究了咖啡因在黑腹果蝇（野生型Canton-S果蝇）中的作用，该果蝇也被观察到对咖啡因有睡眠减少的反应。研究了Canton-S果蝇3日龄、30日龄和50日龄雄性和雌性的午睡和夜间睡眠情况。此外，还研究了在所有神经元（表达elav的细胞）、昼夜节律时钟细胞（表达tim的细胞）和多巴胺能神经元（表达th的细胞）中过表达或沉默dAdoR的转基因果蝇。我们发现，雌性对咖啡因的敏感性高于雄性，并且老年果蝇白天的睡眠时间比年轻果蝇长。然而，咖啡因处理导致在所有神经元、表达tim和表达th的细胞中dAdoR过表达的果蝇午睡减少。相反，dAdoR的沉默增加了午睡时间。因此，果蝇白天睡眠中观察到的差异似乎取决于通过AdoRs的信号传导。
