title: MCH levels in the CSF, brain preproMCH and MCHR1 gene expression during paradoxical sleep deprivation, sleep rebound and chronic sleep restriction.
abstract: Neurons that utilize melanin-concentrating hormone (MCH) as neuromodulator are located in the lateral hypothalamus and incerto-hypothalamic area. These neurons project throughout the central nervous system and play a role in sleep regulation. With the hypothesis that the MCHergic system function would be modified by the time of the day as well as by disruptions of the sleep-wake cycle, we quantified in rats the concentration of MCH in the cerebrospinal fluid (CSF), the expression of the MCH precursor (Pmch) gene in the hypothalamus, and the expression of the MCH receptor 1 (Mchr1) gene in the frontal cortex and hippocampus. These analyses were performed during paradoxical sleep deprivation (by a modified multiple platform technique), paradoxical sleep rebound and chronic sleep restriction, both at the end of the active (dark) phase (lights were turned on at Zeitgeber time zero, ZT0) and during the inactive (light) phase (ZT8). We observed that in control condition (waking and sleep ad libitum), Mchr1 gene expression was larger at ZT8 (when sleep predominates) than at ZT0, both in frontal cortex and hippocampus. In addition, compared to control, disturbances of the sleep-wake cycle produced the following effects: paradoxical sleep deprivation for 96 and 120 h reduced the expression of Mchr1 gene in frontal cortex at ZT0. Sleep rebound that followed 96 h of paradoxical sleep deprivation increased the MCH concentration in the CSF also at ZT0. Twenty-one days of sleep restriction produced a significant increment in MCH CSF levels at ZT8. Finally, sleep disruptions unveiled day/night differences in MCH CSF levels and in Pmch gene expression that were not observed in control (undisturbed) conditions. In conclusion, the time of the day and sleep disruptions produced subtle modifications in the physiology of the MCHergic system.
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Dias Abdo Agamme
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Bruno Frederico
authors.initials: BF
authors.lastname: Aguilar Calegare
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Fernandes
authors.affiliation: Department of Physiology, School of Medicine, Universidad de la República, Montevideo, Uruguay.
authors.forename: Alicia
authors.initials: A
authors.lastname: Costa
authors.affiliation: Department of Physiology, School of Medicine, Universidad de la República, Montevideo, Uruguay.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lagos
authors.affiliation: Department of Physiology, School of Medicine, Universidad de la República, Montevideo, Uruguay. Electronic address: ptortero@fmed.edu.uy.
authors.forename: Pablo
authors.initials: P
authors.lastname: Torterolo
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Vânia
authors.initials: V
authors.lastname: D'Almeida
mesh_terms: D000818:Animals; D005625:Frontal Lobe / Q000378:metabolism; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D007028:Hypothalamic Hormones / Q000134:cerebrospinal fluid* / Q000235:genetics*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000134:cerebrospinal fluid*; D010907:Pituitary Hormones / Q000134:cerebrospinal fluid*; D011498:Protein Precursors / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000235:genetics*; D012892:Sleep Deprivation / Q000378:metabolism*; D012895:Sleep, REM
chemical_list: D007028:Hypothalamic Hormones; C491208:MCHR1 protein, rat; D008543:Melanins; D010907:Pituitary Hormones; C000611046:Pmch protein, rat; D011498:Protein Precursors; D017481:Receptors, Somatostatin; C019463:melanin-concentrating hormone
keywords: Cerebrospinal fluid; Hypothalamus; Melanin-concentrating hormone; Neuropeptide; REM sleep