Effects of Paradoxical Sleep Deprivation on MCH and Hypocretin Systems

Abstract

Melanin-concentrating hormone (MCH) and hypocretins (Hcrt) 1 and 2 are neuropeptides synthesized in the lateral hypothalamic area by neurons that are critical in the regulation of sleep and wakefulness. Their receptors are located in the same cerebral regions, including the frontal cortex and hippocampus. The present study aimed to assess whether 96 hours of paradoxical sleep deprivation alters the functioning of the MCH and hypocretin systems. To do this, in control rats with normal sleep (CTL) and in rats that were deprived of paradoxical sleep (SD), we quantified the following parameters: 1) levels of MCH and hypocretin-1 in the cerebrospinal fluid (CSF); 2) expression of the prepro-MCH (Pmch) and prepro-hypocretin (Hcrt) genes in the hypothalamus; 3) expression of the Mchr1 and Hcrtr1 genes in the frontal cortex and hippocampus; and 4) expression of the Hcrtr2 gene in the hippocampus. These measures were performed at 6 Zeitgeber time (ZT) points of the day (ZTs: 0, 4, 8, 12, 16, and 20). In the SD group, we found higher levels of MCH in the CSF at the beginning of the dark phase. In the frontal cortex, sleep deprivation decreased the expression of Hcrtr1 at ZT0. Moreover, we identified significant differences between the light and dark phases in the expression of Mchr1 and Hcrtr1, but only in the CTL animals. We conclude that there is a day/night modulation in the expression of components of the MCH and hypocretin systems, and this profile is affected by paradoxical sleep deprivation.

Keywords

• hypothalamus
• neuropeptides
• orexin
• circadian rhythm
• REM sleep
• gene expression