title: Histamine Transmission Modulates the Phenotype of Murine Narcolepsy Caused by Orexin Neuron Deficiency.
abstract: Narcolepsy type 1 is associated with loss of orexin neurons, sleep-wake derangements, cataplexy, and a wide spectrum of alterations in other physiological functions, including energy balance, cardiovascular, and respiratory control. It is unclear which narcolepsy signs are directly related to the lack of orexin neurons or are instead modulated by dysfunction of other neurotransmitter systems physiologically controlled by orexin neurons, such as the histamine system. To address this question, we tested whether some of narcolepsy signs would be detected in mice lacking histamine signaling (HDC-KO). Moreover, we studied double-mutant mice lacking both histamine signaling and orexin neurons (DM) to evaluate whether the absence of histamine signaling would modulate narcolepsy symptoms produced by orexin deficiency. Mice were instrumented with electrodes for recording the electroencephalogram and electromyogram and a telemetric arterial pressure transducer. Sleep attacks fragmenting wakefulness, cataplexy, excess rapid-eye-movement sleep (R) during the activity period, and enhanced increase of arterial pressure during R, which are hallmarks of narcolepsy in mice, did not occur in HDC-KO, whereas they were observed in DM mice. Thus, these narcolepsy signs are neither caused nor abrogated by the absence of histamine. Conversely, the lack of histamine produced obesity in HDC-KO and to a greater extent also in DM. Moreover, the regularity of breath duration during R was significantly increased in either HDC-KO or DM relative to that in congenic wild-type mice. Defects of histamine transmission may thus modulate the metabolic and respiratory phenotype of murine narcolepsy.
authors.affiliation: PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bastianini
authors.affiliation: PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Silvani
authors.affiliation: PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Berteotti
authors.affiliation: PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Lo Martire
authors.affiliation: Department of Women & Child Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gary
authors.initials: G
authors.lastname: Cohen
authors.affiliation: Applied Quantum Medical Engineering, Graduate School of Engineering, Tohoku University, Sendai, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.affiliation: Physiologie intégrée du système d'éveil, Centre de recherche en neurosciences de Lyon, INSERM U1028-CNRS UMR 5292 Faculté de Médecine, Université Claude Bernard, Lyon, France.
authors.forename: Jian-Sheng
authors.initials: JS
authors.lastname: Lin
authors.affiliation: PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zoccoli
mesh_terms: D000818:Animals; D001835:Body Weight; D002319:Cardiovascular System / Q000503:physiopathology; D002385:Cataplexy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002149:Energy Intake; D005260:Female; D055786:Gene Knockout Techniques; D006632:Histamine / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D009290:Narcolepsy / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism*; D000068797:Orexins / Q000172:deficiency*; D010641:Phenotype; D012119:Respiration; D015398:Signal Transduction; D012890:Sleep; D014851:Wakefulness
chemical_list: D000068797:Orexins; D006632:Histamine; D006640:Histidine Decarboxylase