A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep.
BACKGROUND
Peptidergic neurons containing the melanin-concentrating hormone (MCH) and the hypocretins (or orexins) are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area. Both types of neurons have been implicated in the integrated regulation of energy homeostasis and body weight. Hypocretin neurons have also been involved in sleep-wake regulation and narcolepsy. We therefore sought to determine whether hypocretin and MCH neurons express Fos in association with enhanced paradoxical sleep (PS or REM sleep) during the rebound following PS deprivation. Next, we compared the effect of MCH and NaCl intracerebroventricular (ICV) administrations on sleep stage quantities to further determine whether MCH neurons play an active role in PS regulation.


RESULTS
Here we show that the MCH but not the hypocretin neurons are strongly active during PS, evidenced through combined hypocretin, MCH, and Fos immunostainings in three groups of rats (PS Control, PS Deprived and PS Recovery rats). Further, we show that ICV administration of MCH induces a dose-dependent increase in PS (up to 200%) and slow wave sleep (up to 70%) quantities.


CONCLUSIONS
These results indicate that MCH is a powerful hypnogenic factor. MCH neurons might play a key role in the state of PS via their widespread projections in the central nervous system.
Verret
Laure
L
CNRS UMR5167, Institut Fédératif des Neurosciences de Lyon (IFR 19), Université Claude Bernard Lyon I, 7 Rue Guillaume Paradin, 69372 LYON Cedex 08, FRANCE. verret@sommeil.univ-lyon1.fr
Goutagny
Romain
R
Fort
Patrice
P
Cagnon
Laurène
L
Salvert
Denise
D
Léger
Lucienne
L
Boissard
Romuald
R
Salin
Paul
P
Peyron
Christelle
C
Luppi
Pierre-Hervé
PH
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D002452:Cell Count; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography; D007028:Hypothalamic Hormones / Q000096:biosynthesis* / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008543:Melanins / Q000096:biosynthesis* / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000096:biosynthesis; D000068797:Orexins; D010907:Pituitary Hormones / Q000096:biosynthesis* / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*
D002352:Carrier Proteins; D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; D016760:Proto-Oncogene Proteins c-fos; C019463:melanin-concentrating hormone