pubmed.ncbi.nlm.nih.gov

Targeting modulation of noradrenalin release in the brain for amelioration of REMS loss-associated effects - PubMed

Review

Targeting modulation of noradrenalin release in the brain for amelioration of REMS loss-associated effects

Abhishek Singh et al. J Transl Int Med. 2015 Jan-Mar.

Abstract

Rapid eye movement sleep (REMS) loss affects most of the physiological processes, and it has been proposed that REMS maintains normal physiological processes. Changes in cultural, social, personal traits and life-style severely affect the amount and pattern of sleep, including REMS, which then manifests symptoms in animals, including humans. The effects may vary from simple fatigue and irritability to severe patho-physiological and behavioral deficits such as cognitive and behavioral dysfunctions. It has been a challenge to identify a molecule(s) that may have a potential for treating REMS loss-associated symptoms, which are very diverse. For decades, the critical role of locus coeruleus neurons in regulating REMS has been known, which has further been supported by the fact that the noradrenalin (NA) level is elevated in the brain after REMS loss. In this review, we have collected evidence from the published literature, including those from this laboratory, and argue that factors that affect REMS and vice versa modulate the level of a common molecule, the NA. Further, NA is known to affect the physiological processes affected by REMS loss. Therefore, we propose that modulation of the level of NA in the brain may be targeted for treating REMS loss-related symptoms. Further, we also argue that among the various ways to affect the release of NA-level, targeting α2 adrenoceptor autoreceptor on the pre-synaptic terminal may be the better option for ameliorating REMS loss-associated symptoms.

Keywords: REMS deprivation; adrenoceptors; locus coeruleus; prazosin; pre- and postsynaptic adrenoceptors.

PubMed Disclaimer

Figures

Figure 1
Figure 1

Noradrenalin (NA) concentration at the synapse is ultimately responsible for manifesting its effect. Its action is mediated by NA-level and its action on the postsynaptic adrenoceptors (ARs). However, the level of NA at the synapse is modulated by changes in either or combination of some or all of the following factors: (i) firing rate of NA-ergic neurons and (ii) changes in (a) TH activity, (b) NA transporter activity, (c) MAO activity and (d) number of α2-ARs and their activation of the NA-ergic neurons. Left panel (A) represents that if any one sub-type of receptor (e.g., by antagonist of α1-ARs as shown here) is blocked, relatively more NA becomes available to act on other sub-types of ARs, which may then express nonspecific side-effects (symptom). Although as an example we have shown that by blocking α1-ARs, a similar effect may be evident by blocking any other one type or combination of ARs types Right panel (B) represents action of NA on the pre-synaptic α2-ARs (autoreceptors) and thus modulating the release of NA

Similar articles

Cited by

References

    1. McNamara P, Capellini I, Harris E, Nunn CL, Barton RA, Preston B. The Phylogeny of Sleep Database: A New Resource for Sleep Scientists. Open Sleep J. 2008;1:11–4. - PMC - PubMed
    1. Capellini I, Barton RA, McNamara P, Preston BT, Nunn CL. Phylogenetic analysis of the ecology and evolution of mammalian sleep. Evolution. 2008;62:1764–76. - PMC - PubMed
    1. Siegel JM. Phylogeny and the function of REM sleep. Behav Brain Res. 1995;69:29–34. - PMC - PubMed
    1. Kushida CA. Sleep Deprivation; basic science, physiology and behavior. Vol. 192. New York: Marcel-Dekker; 2005.
    1. Jouvet-Mounier D, Astic L, Lacote D. Ontogenesis of the states of sleep in rat, cat, and guinea pig during the first postnatal month. Dev Psychobiol. 1970;2:216–39. - PubMed

Publication types

LinkOut - more resources