Melanin-Concentrating Hormone: A New Sleep Factor?

Jaime M. Monti,Pablo Torterolo,Patricia Lagos

doi:10.3389/fneur.2011.00014

Abstract

Neurons containing the neuropeptide melanin-concentrating hormone (MCH) are mainly located in the lateral hypothalamus and the incerto-hypothalamic area, and have widespread projections throughout the brain. While the biological functions of this neuropeptide are exerted in humans through two metabotropic receptors, the MCHR1 and MCHR2, only the MCHR1 is present in rodents. Recently, it has been shown that the MCHergic system is involved in the control of sleep. We can summarize the experimental findings as follows: (1) The areas related to the control of sleep and wakefulness have a high density of MCHergic fibers and receptors. (2) MCHergic neurons are active during sleep, especially during rapid eye movement (REM) sleep. (3) MCH knockout mice have less REM sleep, notably under conditions of negative energy balance. Animals with genetically inactivated MCHR1 also exhibit altered vigilance state architecture and sleep homeostasis. (4) Systemically administered MCHR1 antagonists reduce sleep. (5) Intraventricular microinjection of MCH increases both slow wave sleep (SWS) and REM sleep; however, the increment in REM sleep is more pronounced. (6) Microinjection of MCH into the dorsal raphe nucleus increases REM sleep time. REM seep is inhibited by immunoneutralization of MCH within this nucleus. (7) Microinjection of MCH in the nucleus pontis oralis of the cat enhances REM sleep time and reduces REM sleep latency. All these data strongly suggest that MCH has a potent role in the promotion of sleep. Although both SWS and REM sleep are facilitated by MCH, REM sleep seems to be more sensitive to MCH modulation.

Highlights

Sleep occupies approximately one-third of human’s life
Both slow wave sleep (SWS) and rapid eye movement (REM) sleep are facilitated by melanin-concentrating hormone (MCH), REM sleep seems to be more sensitive to MCH modulation
MELANIN-CONCENTRATING HORMONE In mammals, MCH is a cyclic neuropeptide with 19 aminoacids that has been found predominantly in neurons localized in the lateral hypothalamus and incerto-hypothalamic area (Kawauchi et al, 1983; Skofitsch et al, 1985; Bittencourt et al, 1992)

Summary

INTRODUCTION

Sleep occupies approximately one-third of human’s life. Sleep is not a homogeneous process. MELANIN-CONCENTRATING HORMONE In mammals, MCH is a cyclic neuropeptide with 19 aminoacids that has been found predominantly in neurons localized in the lateral hypothalamus and incerto-hypothalamic area (Kawauchi et al, 1983; Skofitsch et al, 1985; Bittencourt et al, 1992). MCH was described as a circulating hormone isolated from salmon pituitaries, where it induces the aggregation of melanin granules in melanophores; this action results in a pale skin color (Kawauchi et al, 1983). This mechanism lets the animal to camouflage in response to the background color of the environment or in response to stress. The binding of MCH to MCHR1 activates diverse intracellular signaling pathways by coupling to Gi, Gq, and Go proteins, while MCHR2 is known to couple to the Gq protein (Hawes et al, 2000; Sailer et al, 2001)

ANATOMY OF THE MCHergic SYSTEM

Findings

CONCLUSIONS AND FUTURE DIRECTIONS