Role of the L-PGDS-PGD2-DP1 receptor axis in sleep regulation and neurologic outcomes

Sleep

Ottallah, Haneen^1,2,3¹  Ahmad, Abdullah Shafique^1,2,3²  Strickland, Michael^5³  Doré, Sylvain^1,2,3,6,7,8,9⁸  Maciel, Carolina B^4⁹ 

[1] Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL^2;Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL^1;Department of Neurology, University of Florida College of Medicine, Gainesville, FL^4;Department of Neuroscience, University of Florida, Gainesville, FL^9;Department of Pharmaceutics, University of Florida, Gainesville, FL^7;Department of Psychiatry, University of Florida, Gainesville, FL^6;Department of Psychology, University of Florida, Gainesville, FL^8;Division of Biology and Biomedical Sciences, Washington University in Saint Louis, Saint Louis, MO^5;McKnight Brain Institute, University of Florida, Gainesville, FL^3

关键词: animal models;    brain injuries;    DP1 receptor;    eicosanoids;    inflammation;    outcome assessments;    poststroke sleep disturbance;    prostaglandin D2;    prostaglandin receptors;    sleep apnea;   

DOI  :  10.1093/sleep/zsz073

学科分类：生理学

来源: American Academy of Sleep Medicine

【 摘 要 】

To meet the new challenges of modern lifestyles, we often compromise a good night’s sleep. In preclinical models as well as in humans, a chronic lack of sleep is reported to be among the leading causes of various physiologic, psychologic, and neurocognitive deficits. Thus far, various endogenous mediators have been implicated in inter-regulatory networks that collectively influence the sleep-wake cycle. One such mediator is the lipocalin-type prostaglandin D2 synthase (L-PGDS)-Prostaglandin D2 (PGD2)-DP1 receptor (L-PGDS-PGD2-DP1R) axis. Findings in preclinical models confirm that DP1R are predominantly expressed in the sleep-regulating centers. This finding led to the discovery that the L-PGDS-PGD2-DP1R axis is involved in sleep regulation. Furthermore, we showed that the L-PGDS-PGD2-DP1R axis is beneficial in protecting the brain from ischemic stroke. Protein sequence homology was also performed, and it was found that L-PGDS and DP1R share a high degree of homology between humans and rodents. Based on the preclinical and clinical data thus far pertaining to the role of the L-PGDS-PGD2-DP1R axis in sleep regulation and neurologic conditions, there is optimism that this axis may have a high translational potential in human therapeutics. Therefore, here the focus is to review the regulation of the homeostatic component of the sleep process with a special focus on the L-PGDS-PGD2-DP1R axis and the consequences of sleep deprivation on health outcomes. Furthermore, we discuss whether the pharmacological regulation of this axis could represent a tool to prevent sleep disturbances and potentially improve outcomes, especially in patients with acute brain injuries.

【 授权许可】

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