Estradiol influences adenosinergic signaling and nonrapid eye movement sleep need in adult female rats

Sleep

article

Smith, Philip C¹  Phillips, Derrick J¹  Pocivavsek, Ana²  Byrd, Carissa A¹  Viechweg, Shaun S¹  Hampton, Brian³  Mong, Jessica A¹ 

[1] Department of Pharmacology, University of Maryland Baltimore;Department of Pharmacology, Physiology, and Neuroscience, School of Medicine, University of South Carolina;Protein Analysis Laboratory, Center for Innovative Biomedical Resources, University of Maryland Baltimore

关键词: estradiol;    adenosine;    median preoptic nucleus;    sleep;   

DOI  :  10.1093/sleep/zsab225

学科分类：生理学

来源: American Academy of Sleep Medicine

【 摘 要 】

Gonadal steroids and gender are risk factors for sleep disruptions and insomnia in women. However, the relationship between ovarian steroids and sleep is poorly understood. In rodent models, estradiol (E2) suppresses sleep in females suggesting that E2 may reduce homeostatic sleep need. The current study investigates whether E2 decreases sleep need and the potential mechanisms that govern E2 suppression of sleep. Our previous findings suggest that the median preoptic nucleus (MnPO) is a key nexus for E2 action on sleep. Using behavioral, neurochemical, and pharmacological approaches, we tested whether (1) E2 influenced the sleep homeostat and (2) E2 influenced adenosine signaling in the MnPO of adult female rats. In both unrestricted baseline sleep and recovery sleep from 6-h sleep deprivation, E2 significantly reduced nonrapid eye movement (NREM) sleep-delta power, NREM-slow wave activity (NREM-SWA, 0.5–4.0 Hz), and NREM-delta energy suggesting that E2 decreases homeostatic sleep need. However, coordinated with E2-induced changes in physiological markers of homeostatic sleep was a marked increase in MnPO extracellular adenosine (a molecular marker of homeostatic sleep need) during unrestricted and recovery sleep in E2-treated but not oil control animals. While these results seemed contradictory, systemically administered E2 blocked the ability of CGS-21680 (adenosine A2A receptor agonist) microinjected into the MnPO to increase NREM sleep suggesting that E2 may block adenosine signaling. Together, these findings provide evidence that E2 may attenuate the local effects of the A2A receptors in the MnPO, which in turn may underlie estrogenic suppression of sleep behavior as well as changes in homeostatic sleep need.

【 授权许可】

All Rights reserved