Impaired histaminergic neurotransmission in children with narcolepsy type 1

Franco, Patricia; Dauvilliers, Yves; Inocente, Clara Odília; Guyon, Aurore; Villanueva, Carine; Raverot, Véronique; Plancoulaine, Sabine; Lin, Jian‐Sheng

doi:10.1111/cns.13057

Cited by 20 publications

(14 citation statements)

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“…Regardless, our data support the view that at least on the C57Bl/6J background, congenital orexin peptide deficiency is sufficient to increase histamine neuron number in adulthood. This result may represent a homeostatic compensation for the loss of orexin peptides, or for an impairment of histaminergic neurotransmission, recently described in narcoleptic children close to disease onset ( Franco et al, 2019 ).…”

Section: Discussionmentioning

confidence: 81%

Orexin/Hypocretin and Histamine Cross-Talk on Hypothalamic Neuron Counts in Mice

et al. 2021

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The loss of hypothalamic neurons that produce wake-promoting orexin (hypocretin) neuropeptides is responsible for narcolepsy type 1 (NT1). While the number of histamine neurons is increased in patients with NT1, results on orexin-deficient mouse models of NT1 are inconsistent. On the other hand, the effect of histamine deficiency on orexin neuron number has never been tested on mammals, even though histamine has been reported to be essential for the development of a functional orexin system in zebrafish. The aim of this study was to test whether histamine neurons are increased in number in orexin-deficient mice and whether orexin neurons are decreased in number in histamine-deficient mice. The hypothalamic neurons expressing L-histidine decarboxylase (HDC), the histamine synthesis enzyme, and those expressing orexin A were counted in four orexin knock-out mice, four histamine-deficient HDC knock-out mice, and four wild-type C57BL/6J mice. The number of HDC-positive neurons was significantly higher in orexin knock-out than in wild-type mice (2,502 ± 77 vs. 1,800 ± 213, respectively, one-tailed t-test, P = 0.011). Conversely, the number of orexin neurons was not significantly lower in HDC knock-out than in wild-type mice (2,306 ± 56 vs. 2,320 ± 120, respectively, one-tailed t-test, P = 0.459). These data support the view that orexin peptide deficiency is sufficient to increase histamine neuron number, supporting the involvement of the histamine waking system in the pathophysiology of NT1. Conversely, these data do not support a significant role of histamine in orexin neuron development in mammals.

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Section: Discussionmentioning

confidence: 81%

Orexin/Hypocretin and Histamine Cross-Talk on Hypothalamic Neuron Counts in Mice

et al. 2021

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“…However, in the few patients reported in our study, no differences were found in CSF hypocretin‐1 levels between children and adults. We recently reported an impairment in histamine neurotransmission, another brain wake‐promoting system, in children with NT1, 41 which was not found in adults 42 . Histaminergic neurons could be also involved as studies in animal models have suggested that lack of either hypocretin or histamine could lead to a mild obesity 43,44 .…”

Section: Discussionmentioning

confidence: 99%

Narcolepsy with cataplexy: Does age at diagnosis change the clinical picture?

et al. 2020

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Objective To compare symptoms and sleep characteristics in patients diagnosed with narcolepsy‐cataplexy (NC) before and after the age of 18 years. Methods De novo patients with NC diagnosis completed a standardized questionnaire and interview, followed by a sleep study. The clinical and sleep measures were compared between patients diagnosed before (46 children, median age: 12 year old) and after (46 adults, median age: 28.5 year old) 18 years of age. Results The frequency of obesity (54% vs 17%), night eating (29% vs 7%), parasomnia (89% vs 43%), sleep talking (80% vs 34%), and sleep drunkenness (69% vs 24%) were higher in children than in adults, the frequency of sleep paralysis was lower (20% vs 55%) but the frequency of cataplexy and the severity of sleepiness were not different. Children scored higher than adults at the attention‐deficit/hyperactivity disorder (ADHD) scale. Depressive feelings affected not differently children (24%) and adults (32%). However, adults had lower quality of life than children. There was no difference between groups for insomnia and fatigue scores. Quality of life was essentially impacted by depressive feelings in both children and adults. Obstructive apnea‐hypopnea index (OAHI) was lower in children with higher mean and minimal oxygen saturation than in adults. No between‐group differences were found at the multiple sleep latency test. The body mass index (z‐score) was correlated with OAHI (r = .32). Conclusion At time of NC diagnosis, children have more frequent obesity, night eating, parasomnia, sleep talking, drunkenness, and ADHD symptoms than adults, even if sleepiness and cataplexy do not differ. These differences should be considered to ensure a prompt diagnosis.

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“…Since brain histamine has a strong impact on the vigilant state, the involvement of the histaminergic system in narcolepsy has been extensively studied. Several reports showed lower histamine levels in the CSF of narcolepsy patients (Kanbayashi et al, 2009; Nishino et al, 2009) and a recent study indicated the involvement of impaired histaminergic neurotransmission in narcoleptic children (Franco et al, 2019). However, the association of CSF histamine levels with narcolepsy was not confirmed in other studies (Croyal et al, 2011; Dauvilliers et al, 2012), indicating that the causative role of histaminergic dysfunction in narcolepsy is still inconclusive.…”

Section: Box 1: Neuronal Histaminergic System and Related Diseasesmentioning

confidence: 99%

“…n K i value of histamine to 0.4-nM [ 125 I]-iodoaminopotentidine in the homogenates of rat H 2 R transfected Sf9 cells (Beukers et al, 1997). o K i value of histamine to 2-nM [ 3 H]-tiotidine in the homogenates of guinea pig lung parenchyma (Foreman et al, 1985). ; Oda et al (2000).…”

Section: Histamine H 3 Receptormentioning

confidence: 99%

Histaminergic neurons in the tuberomammillary nucleus as a control centre for wakefulness

Yoshikawa

Nakamura

Yanai

2020

British J Pharmacology

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Histamine plays pleiotropic roles as a neurotransmitter in the physiology of brain function, this includes the maintenance of wakefulness, appetite regulation and memory retrieval. Since numerous studies have revealed an association between histaminergic dysfunction and diverse neuropsychiatric disorders, such as Alzheimer's disease and schizophrenia, a large number of compounds acting on the brain histamine system have been developed to treat neurological disorders. In 2016, pitolisant, which was developed as a histamine H3 receptor inverse agonist by Schwartz and colleagues, was launched for the treatment of narcolepsy, emphasising the prominent role of brain histamine on wakefulness. Recent advances in neuroscientific techniques such as chemogenetic and optogenetic approaches have led to remarkable progress in the understanding of histaminergic neural circuits essential for the control of wakefulness. In this review article, we summarise the basic knowledge about the histaminergic nervous system and the mechanisms underlying sleep/wake regulation that are controlled by the brain histamine system. LINKED ARTICLES This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.4/issuetoc

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Impaired histaminergic neurotransmission in children with narcolepsy type 1

Cited by 20 publications

References 40 publications

Orexin/Hypocretin and Histamine Cross-Talk on Hypothalamic Neuron Counts in Mice

Orexin/Hypocretin and Histamine Cross-Talk on Hypothalamic Neuron Counts in Mice

Narcolepsy with cataplexy: Does age at diagnosis change the clinical picture?

Histaminergic neurons in the tuberomammillary nucleus as a control centre for wakefulness

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