Dual orexin receptor antagonists as promising therapeutics for Alzheimer's disease.

We examine the relationship between sleep, glymphatics and Alzheimer's disease (AD), and recent work questioning glymphatic clearance during sleep. We highlight a need for understanding glymphatic and/or other mechanism of clearance during sleep, and review glymphatic flow measurement methods. Further, we explore dual orexin receptor antagonists (DORAs) potential to mitigate AD sleep disturbances and enhance clearance.

Hindbrain orexin 1 receptors blunt intake suppression by gastrointestinal nutrients and cholecystokinin in male rats.

Hypothalamic orexin neurons project to many brain areas, including hindbrain structures such as the nucleus of the solitary tract (NTS) and area postrema (AP), where orexin 1 receptors (OX1Rs) are expressed. Hindbrain administration of orexin-A increases feeding and meal size, and blockade of hindbrain OX1Rs with the selective antagonist SB334867 has the opposite effect. Here we asked whether hindbrain OX1R stimulation or blockade alter rats' sensitivity to gastrointestinal satiety signals.

Intermittent High-Fat Diet Intake Reduces Sensitivity to Intragastric Nutrient Infusion and Exogenous Amylin in Female Rats.

Objective: Intermittent (INT) access to a high-fat diet (HFD) can induce excessive-intake phenotypes in rodents. This study hypothesized that impaired satiation responses contribute to elevated intake in an INT-HFD access model.

Methods: First, this study characterized the intake and meal patterns of female rats that were subjected to an INT HFD in which a 45% HFD was presented for 20 hours every fourth day.