Melanin-Concentrating Hormone (MCH): Role in REM Sleep and Depression

Abstract

The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons of the lateral sector of the posterior hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR) and median (MR) raphe nuclei, which are involved in the control of sleep and mood. Major Depression (MD) is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability, and anhedonia. A short REM sleep latency (i.e., the interval between sleep onset and the first REM sleep period), as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline) and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons. Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD.

Stress Impacts the Regulation Neuropeptides in the Rat Hippocampus and Prefrontal Cortex

“…In addition to this, peptide E.IGDEENSAKFPI(‐.98).G derived from Pro‐MCH precursor was also downregulated −48% ( p = 0.037) in the PFC region. It has been reported that the neuropeptide MCH plays a role in rapid eye movement (REM) sleep and is involved in the pathophysiology of depression . Some authors have demonstrated that MCH receptor‐1 antagonist (SNAP‐7941) possesses antidepressant and anxiolytic effects in animal models of depressive disorder .…”

Melanin‐concentrating hormone peptidergic system: Comparative morphology between muroid species

“…Areas linked to reward are innervated by MCH/NEI neurons, including light innervation of the caudate‐putamen and moderate innervation of the ventral tegmental area, with MCH/NEI‐ir fibers contacting dopaminergic neurons in the latter, supporting the circuit suggested by Domingos et al (). Actions of MCH on learning, memory consolidation/retrieval, and emotion (Le Barillier et al, ; Monzon et al, ; Sita et al, ; Torterolo et al, ) also had a clear anatomical substrate in M musculus mice, with a dense innervation of the medial septal nucleus and the dorsal part of the hippocampal formation, similar to Rattus (Lima et al, ). Similar observations were made for autonomic modulation mediated by the nucleus of the solitary tract and the PVH (Abbott et al, ; Brown, Chitravanshi, Kawabe, & Sapru, ), sleep and arousal mediated by the dorsal raphe and the ventrolateral periaqueductal gray matter (Clément et al, ; Lagos et al, ; Lagos, Torterolo, Jantos, & Monti, ), and sensory integration through projections to olfactory areas and the medial septal nucleus (Adams et al, ; Miller et al, ).…”

Ciliary melanin‐concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex‐independent manner

“…ior (Bouret, Draper, & Simerly, 2004;Stanley & Leibowitz, 1985;Stratford & Kelley, 1997), and injections of MCH or MCHR1 antagonist in these areas have been shown to modulate ingestion (Abbott et al, 2003;Georgescu, Sears, & Hommel, 2005 (Segal-Lieberman et al, 2003) and the animal emotional state (Borowsky et al, 2002). Emotional state and sleep may also be regulated through the dorsal and median raphe nuclei (Monti, Pandi-Perumal, & Torterolo, 2018;Torterolo et al, 2015;Urbanavicius, Lagos, López, Torterolo, & Scorza, 2018). The high density of MCHR1 in the caudate-putamen and its presence in the ventral tegmental area also allows MCH to act on reward circuits through the mesolimbic pathway (Domingos et al, 2013).…”