Histamine in murine narcolepsy: What do genetic and immune models tell us?

Autor: Anne-Laure Morel, Silvia Melzi, Roland S. Liblau, Céline Scoté-Blachon, Yves Dauvilliers, Christelle Peyron
Přispěvatelé: Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Peyron, Christelle, APPEL À PROJETS GÉNÉRIQUE 2018 - Physiopathologie de la narcolepsie de type 1 - - NARCO-T12018 - ANR-18-CE17-0014 - AAPG2018 - VALID, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), ANR-18-CE17-0014,NARCO-T1,Physiopathologie de la narcolepsie de type 1(2018)
Rok vydání: 2021
Předmět:
MESH: Histamine* / metabolism
[SDV]Life Sciences [q-bio]
MESH: Histidine Decarboxylase / genetics
Histidine Decarboxylase
Mixed Function Oxygenases
Mice
chemistry.chemical_compound
MESH: Narcolepsy* / genetics
0302 clinical medicine
MESH: Orexins / metabolism
MESH: Animals
hypothalamus
0303 health sciences
Microglia
General Neuroscience
MESH: Mixed Function Oxygenases
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
Hypothalamus
[SDV.IMM]Life Sciences [q-bio]/Immunology
Histamine
medicine.medical_specialty
[SDV.IMM] Life Sciences [q-bio]/Immunology
Biology
Pathology and Forensic Medicine
03 medical and health sciences
Internal medicine
medicine
Animals
Humans
RNA
Messenger
sleep
MESH: Mice
Neuroinflammation
MESH: RNA
Messenger
Narcolepsy
030304 developmental biology
MESH: Narcolepsy* / metabolism
Orexins
MESH: Humans
Histaminergic
medicine.disease
Pons
Orexin
Endocrinology
orexin
nervous system
chemistry
Neurology (clinical)
hypocretin
030217 neurology & neurosurgery
Zdroj: Brain Pathology
Brain Pathology, Wiley, 2021, ⟨10.1111/bpa.13027⟩
Brain Pathology, 2022, 32 (2), pp.e13027. ⟨10.1111/bpa.13027⟩
ISSN: 1750-3639
1015-6305
DOI: 10.1111/bpa.13027
Popis: International audience; An increased number of histaminergic neurons, identified by labeling histidine-decarboxylase (HDC) its synthesis enzyme, was unexpectedly found in patients with narcolepsy type 1 (NT1). In quest for enlightenment, we evaluate whether an increase in HDC cell number and expression level would be detected in mouse models of the disease, in order to provide proof of concepts reveling possible mechanisms of compensation for the loss of orexin neurons, and/or of induced expression as a consequence of local neuroinflammation, a state that likely accompanies NT1. To further explore the compensatory hypothesis, we also study the noradrenergic wake-promoting system. Immunohistochemistry for HDC, orexin, and melanin-concentrating hormone (MCH) was used to count neurons. Quantitative-PCR of HDC, orexin, MCH, and tyrosine-hydroxylase was performed to evaluate levels of mRNA expression in the hypothalamus or the dorsal pons. Both quantifications were achieved in genetic and neuroinflammatory models of narcolepsy with major orexin impairment, namely the orexin-deficient (Orex-KO) and orexin-hemagglutinin (Orex-HA) mice respectively. The number of HDC neurons and mRNA expression level were unchanged in Orex-KO mice compared to controls. Similarly, we found no change in tyrosine-hydroxylase mRNA expression in the dorsal pons between groups. Further, despite the presence of protracted local neuroinflammation as witnessed by the presence of reactive microglia, we found no change in the number of neurons nor the expression of HDC in Orex-HA mice compared to controls. Importantly, no correlation was found in all conditions between HDC and orexin. Our findings indicate that, in mice, the expression of histamine and noradrenalin, two wake-promoting systems, are not modulated by orexin level whether the lack of orexin is constitutive or induced at adult age, showing thus no compensation. They also show no recruitment of histamine by local neuroinflammation. Further studies will be needed to further define the role of histamine in the pathophysiology of NT1.
Databáze: OpenAIRE
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