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The histaminergic network in the brain: basic organization and role in disease
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Journal Article
The histaminergic network in the brain: basic organization and role in disease
2013
Overview
Key Points
The histaminergic system is implicated in various brain disorders. A mutation in the gene encoding histidine decarboxylase, the histamine synthesizing enzyme, has been identified to be a cause of dominantly inherited Guilles de la Tourette syndrome.
In clinical trials, histamine H
2
receptor antagonists have shown therapeutic efficacy for schizophrenia. and histamine H
3
receptor antagonists have shown promise for combating daytime sleepiness in patients with narcolepsy.
In experimental allergic encephalomyelitis, a mouse model of multiple sclerosis, animals lacking histidine decarboxylase (and hence histamine synthesis) or histamine receptors show abnormal development of disease symptoms.
Histamine regulates feeding, obesity and the actions of leptin via histamine H
1
receptor signalling in the hypothalamus; antipsychotic drugs bind to H
1
receptors and cause obesity through this mechanism.
Histamine H
3
receptor antagonists regulate alcohol self-administration and conditioned place preference in rodents, probably through a modulatory action on dopaminergic signalling. These drugs have already been tested for other disease conditions, so clinical trials on alcoholism could be carried out without extensive early phase studies.
The histaminergic neuromodulatory system has important roles in in the regulation of cognition, sleep and wakefulness, and feeding and energy balance. In this Review, Panula and Nuutinen briefly explore histamine's physiological functions before focusing on its roles in various brain disorders.
Histamine acts as a modulatory neurotransmitter in the mammalian brain. It has an important role in the maintenance of wakefulness, and dysfunction in the histaminergic system has been linked to narcolepsy. Recent evidence suggests that aberrant histamine signalling in the brain may also be a key factor in Gilles de la Tourette syndrome, Parkinson's disease and addictive behaviours. Furthermore, multiple sclerosis (MS) and experimental autoimmune encephalitis, which is an often-used model for MS, are associated with changes in the histaminergic system. This Review explores the possible roles of brain histamine in the mechanisms underlying these diseases.
Publisher
Nature Publishing Group UK,Nature Publishing Group
