Histamine: neural circuits and new medications

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Title: Histamine: neural circuits and new medications
Authors: Scammell, TE
Jackson, AC
Franks, NP
Wisden, W
Dauvilliers, Y
Item Type: Journal Article
Abstract: Histamine was first identified in the brain about 50 years ago, but only in the last few years have researchers gained an understanding of how it regulates sleep/wake behavior. We provide a translational overview of the histamine system, from basic research to new clinical trials demonstrating the usefulness of drugs that enhance histamine signaling. The tuberomammillary nucleus is the sole neuronal source of histamine in the brain, and like many of the arousal systems, histamine neurons diffusely innervate the cortex, thalamus, and other wake-promoting brain regions. Histamine has generally excitatory effects on target neurons, but paradoxically, histamine neurons may also release the inhibitory neurotransmitter GABA. New research demonstrates that activity in histamine neurons is essential for normal wakefulness, especially at specific circadian phases, and reducing activity in these neurons can produce sedation. The number of histamine neurons is increased in narcolepsy, but whether this affects brain levels of histamine is controversial. Of clinical importance, new compounds are becoming available that enhance histamine signaling, and clinical trials show that these medications reduce sleepiness and cataplexy in narcolepsy.
Issue Date: 31-Jan-2019
Date of Acceptance: 6-Aug-2018
URI: http://hdl.handle.net/10044/1/63300
DOI: https://doi.org/10.1093/sleep/zsy183
ISSN: 0161-8105
Publisher: Oxford University Press (OUP)
Journal / Book Title: Sleep
Volume: 42
Issue: 1
Copyright Statement: © 2018 Sleep Research Society. Published by Oxford University Press [on behalf of the Sleep Research Society]. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Wellcome Trust
UK DRI Ltd
Wellcome Trust
Wellcome Trust
Funder's Grant Number: 107841/Z/15/Z
4050641385
107839/Z/15/Z
107841/Z/15/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
histamine
H1R
H3R
pitolisant
diphenhydramine
narcolepsy
sedative
sleepiness
tuberomammillary nucleus
orexin
CEREBROSPINAL-FLUID HISTAMINE
SLEEP-WAKING DISCHARGE
EYE-MOVEMENT SLEEP
TUBEROMAMMILLARY NUCLEUS
POSTERIOR HYPOTHALAMUS
H-3 RECEPTOR
ELECTROPHYSIOLOGICAL DIVERSITY
GABA(A) RECEPTORS
SYNAPTIC RELEASE
BRAIN HISTAMINE
06 Biological Sciences
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Neurology & Neurosurgery
Publication Status: Published
Online Publication Date: 2018-09-18
Appears in Collections:Faculty of Natural Sciences



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