CC BY-NC-ND 4.0 · Sleep Sci
DOI: 10.1055/s-0044-1782171
Original Article

Effects of Paradoxical Sleep Deprivation on MCH and Hypocretin Systems

1   Departamento de Psicobiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil
,
1   Departamento de Psicobiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil
,
2   Department of Physiology, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
,
1   Departamento de Psicobiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil
› Author Affiliations
Funding The present study was supported by AFIP, FAPESP, CAPES, and CNPq (VD'A 304995/2014-2 and 304588/2021-0). ALAA was the recipient of a scholarship from FAPESP (#2015/05666-2).

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.

Data Availability

The data that support the findings of the present study are available from the corresponding author upon reasonable request.




Publication History

Received: 17 December 2022

Accepted: 20 December 2023

Article published online:
21 May 2024

© 2024. Brazilian Sleep Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 
  • References

  • 1 Peyron C, Tighe DK, van den Pol AN. et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 1998; 18 (23) 9996-10015
  • 2 Bittencourt JC, Diniz GB. Neuroanatomical Structure of the MCH System. In: Pandi Perumal SR, Torterolo P, Monti J. eds. Melanin-concentrating Hormone and Sleep. Switzerland:: Springer; 2018: 1-46
  • 3 Torterolo P, Sampogna S, Morales FR, Chase MH. MCH-containing neurons in the hypothalamus of the cat: searching for a role in the control of sleep and wakefulness. Brain Res 2006; 1119 (01) 101-114
  • 4 Costa A, Castro-Zaballa S, Lagos P, Chase MH, Torterolo P. Distribution of MCH-containing fibers in the feline brainstem: Relevance for REM sleep regulation. Peptides 2018; 104: 50-61
  • 5 Costa A, Monti J, Torterolo P. Hypocretin (orexin) immunoreactivity in the feline midbrain: Relevance for the generation of wakefulness. J Chem Neuroanat 2020; 105: 101769
  • 6 Li SB, de Lecea L. The hypocretin (orexin) system: from a neural circuitry perspective. Neuropharmacology 2020; 167: 107993
  • 7 Tan CP, Sano H, Iwaasa H. et al. Melanin-concentrating hormone receptor subtypes 1 and 2: species-specific gene expression. Genomics 2002; 79 (06) 785-792
  • 8 Sakurai T, Amemiya A, Ishii M. et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998; 92 (04) 573-585
  • 9 Hervieu GJ, Cluderay JE, Harrison DC, Roberts JC, Leslie RA. Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord. Neuroscience 2001; 103 (03) 777-797
  • 10 Saito Y, Cheng M, Leslie FM, Civelli O. Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain. J Comp Neurol 2001; 435 (01) 26-40
  • 11 De Lecea L. Twenty-Three Years of Hypocretins: The “Rosetta Stone” of Sleep/Arousal Circuits. Front Neurol Neurosci 2021; 45: 1-10
  • 12 Bandaru SS, Khanday MA, Ibrahim N, Naganuma F, Vetrivelan R. Sleep-Wake Control by Melanin-Concentrating Hormone (MCH) Neurons: a Review of Recent Findings. Curr Neurol Neurosci Rep 2020; 20 (12) 55
  • 13 Potter LE, Burgess CR. The melanin-concentrating hormone system as a target for the treatment of sleep disorders. Front Neurosci 2022; 16: 952275
  • 14 Pizza F, Barateau L, Dauvilliers Y, Plazzi G. The orexin story, sleep and sleep disturbances. J Sleep Res 2022; 31 (04) e13665
  • 15 Bouâouda H, Jha PK. Orexin and MCH neurons: regulators of sleep and metabolism. Front Neurosci 2023; 17: 1230428
  • 16 Hassani OK, Lee MG, Jones BE. Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep-wake cycle. Proc Natl Acad Sci U S A 2009; 106 (07) 2418-2422
  • 17 Feng H, Wen SY, Qiao QC. et al. Orexin signaling modulates synchronized excitation in the sublaterodorsal tegmental nucleus to stabilize REM sleep. Nat Commun 2020; 11 (01) 3661
  • 18 Izawa S, Chowdhury S, Miyazaki T. et al. REM sleep-active MCH neurons are involved in forgetting hippocampus-dependent memories. Science 2019; 365 (6459) 1308-1313
  • 19 Blanco-Centurion C, Luo S, Spergel DJ. et al. Dynamic Network Activation of Hypothalamic MCH Neurons in REM Sleep and Exploratory Behavior. J Neurosci 2019; 39 (25) 4986-4998
  • 20 Liew SC, Aung T. Sleep deprivation and its association with diseases- a review. Sleep Med 2021; 77: 192-204
  • 21 Naiman R. Dreamless: the silent epidemic of REM sleep loss. Ann N Y Acad Sci 2017; 1406 (01) 77-85
  • 22 Aschoff J, Wever R. Circadian rhythms of finches in light-dark cycles with interposed twilights. Comp Biochem Physiol 1965; 16 (04) 507-514
  • 23 Machado RB, Hipólide DC, Benedito-Silva AA, Tufik S. Sleep deprivation induced by the modified multiple platform technique: quantification of sleep loss and recovery. Brain Res 2004; 1004 (1-2): 45-51
  • 24 Muzur A, Pace-Schott EF, Hobson JA. The prefrontal cortex in sleep. Trends Cogn Sci 2002; 6 (11) 475-481
  • 25 Durán E, Oyanedel CN, Niethard N, Inostroza M, Born J. Sleep stage dynamics in neocortex and hippocampus. Sleep 2018;41(06):
  • 26 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25 (04) 402-408
  • 27 Noble EE, Hahn JD, Konanur VR. et al. Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone. Cell Metab 2018; 28 (01) 55-68.e7
  • 28 Veening JG, Barendregt HP. The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review. Cerebrospinal Fluid Res 2010; 7: 1
  • 29 Dias Abdo Agamme AL, Aguilar Calegare BF, Fernandes L. et al. MCH levels in the CSF, brain preproMCH and MCHR1 gene expression during paradoxical sleep deprivation, sleep rebound and chronic sleep restriction. Peptides 2015; 74: 9-15
  • 30 Gerics B, Szalay F, Sótonyi P, Jancsik V. Diurnal variation of the melanin-concentrating hormone level in the hypothalamus. Acta Biol Hung 2017; 68 (01) 14-21
  • 31 Galvão MdeO, Sinigaglia-Coimbra R, Kawakami SE, Tufik S, Suchecki D. Paradoxical sleep deprivation activates hypothalamic nuclei that regulate food intake and stress response. Psychoneuroendocrinology 2009; 34 (08) 1176-1183
  • 32 Moore RY, Lenn NJ. A retinohypothalamic projection in the rat. J Comp Neurol 1972; 146 (01) 1-14
  • 33 Jha PK, Bouâouda H, Gourmelen S. et al. Sleep Deprivation and Caffeine Treatment Potentiate Photic Resetting of the Master Circadian Clock in a Diurnal Rodent. J Neurosci 2017; 37 (16) 4343-4358
  • 34 Pelluru D, Konadhode R, Shiromani PJ. MCH neurons are the primary sleep-promoting group. Sleep 2013; 36 (12) 1779-1781
  • 35 Freudenberger CB. A comparison of the Wistar albino and the Long-Evans hybrid strain of the Norway rat. Am J Anat 1932; 50: 293-349
  • 36 Abel EL. Response to alarm substance in different rat strains. Physiol Behav 1992; 51 (02) 345-347
  • 37 Stütz AM, Staszkiewicz J, Ptitsyn A, Argyropoulos G. Circadian expression of genes regulating food intake. Obesity (Silver Spring) 2007; 15 (03) 607-615
  • 38 Wang D, Opperhuizen AL, Reznick J. et al. Effects of feeding time on daily rhythms of neuropeptide and clock gene expression in the rat hypothalamus. Brain Res 2017; 1671: 93-101
  • 39 Viale A, Ortola C, Hervieu G. et al. Cellular localization and role of prohormone convertases in the processing of pro-melanin concentrating hormone in mammals. J Biol Chem 1999; 274 (10) 6536-6545
  • 40 Deboer T, Overeem S, Visser NA. et al. Convergence of circadian and sleep regulatory mechanisms on hypocretin-1. Neuroscience 2004; 129 (03) 727-732
  • 41 Desarnaud F, Murillo-Rodriguez E, Lin L. et al. The diurnal rhythm of hypocretin in young and old F344 rats. Sleep 2004; 27 (05) 851-856
  • 42 Pedrazzoli M, D'Almeida V, Martins PJ. et al. Increased hypocretin-1 levels in cerebrospinal fluid after REM sleep deprivation. Brain Res 2004; 995 (01) 1-6
  • 43 Carter ME, Schaich Borg J, de Lecea L. The brain hypocretins and their receptors: mediators of allostatic arousal. Curr Opin Pharmacol 2009; 9 (01) 39-45
  • 44 Chase MH. A unified survival theory of the functioning of the hypocretinergic system. J Appl Physiol 2013; 115 (07) 954-971
  • 45 Zhang R, Lahens NF, balance HI, Hughes ME, Hogenesch JB. A circadian gene expression atlas in mammals: implications for biology and medicine. Proc Natl Acad Sci U S A 2014; 111 (45) 16219-16224
  • 46 Fujiki N, Yoshida Y, Ripley B, Honda K, Mignot E, Nishino S. Changes in CSF hypocretin-1 (orexin A) levels in rats across 24.  . hours and in response to food deprivation. Neuroreport 2001; 12 (05) 993-997
  • 47 Taheri S, Sunter D, Dakin C. et al. Diurnal variation in orexin A immunoreactivity and prepro-orexin mRNA in the rat central nervous system. Neurosci Lett 2000; 279 (02) 109-112
  • 48 Hernandez ME, Watkins JM, Vu J, Hayward LF. DOCA/salt hypertension alters Period1 and orexin-related gene expression in the medulla and hypothalamus of male rats: Diurnal influences. Auton Neurosci 2018; 210: 34-43
  • 49 Deboer T. Investigating sleep homeostasis using an unusual instability. Am J Physiol Regul Integr Comp Physiol 2004; 287 (01) R8-R9
  • 50 D'Almeida V, Hipólide DC, Raymond R. et al. Opposite effects of sleep rebound on orexin OX1 and OX2 receptor expression in rat brain. Brain Res Mol Brain Res 2005; 136 (1-2): 148-157
  • 51 Longordo F, Kopp C, Lüthi A. Consequences of sleep deprivation on neurotransmitter receptor expression and function. Eur J Neurosci 2009; 29 (09) 1810-1819
  • 52 Hipólide DC, Suchecki D, Pimentel de Carvalho Pinto A, Chiconelli Faria E, Tufik S, Luz J. Paradoxical sleep deprivation and sleep recovery: effects on the hypothalamic-pituitary-adrenal axis activity, energy balance and body composition of rats. J Neuroendocrinol 2006; 18 (04) 231-238
  • 53 Suchecki D, Tufik S. Social stability attenuates the stress in the modified multiple platform method for paradoxical sleep deprivation in the rat. Physiol Behav 2000; 68 (03) 309-316
  • 54 Smith DG, Davis RJ, Rorick-Kehn L. et al. Melanin-concentrating hormone-1 receptor modulates neuroendocrine, behavioral, and corticolimbic neurochemical stress responses in mice. Neuropsychopharmacology 2006; 31 (06) 1135-1145
  • 55 Bittencourt JC, Presse F, Arias C. et al. The melanin-concentrating hormone system of the rat brmmunen immuno- and hybridization histochemical characterization. J Comp Neurol 1992; 319 (02) 218-245
  • 56 Andersen ML, Tufik S. Animal models as tools in ethical biomedical research. São Paulo: Unifesp. 2010.