Decreased brain histamine content in hypocretin/orexin receptor-2 mutated narcoleptic dogs

• Published in: Neuroscience letters Vol. 313; no. 3; pp. 125 - 128
• Main Authors: Nishino, Seiji, Fujiki, Nobuhiro, Ripley, Beth, Sakurai, Eiko, Kato, Motohisa, Watanabe, Takehiko, Mignot, Emmanuel, Yanai, Kazuhiko
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 09.11.2001; Elsevier
• Subjects: 3,4-Dihydroxyphenylacetic Acid - analysis; 3,4-Dihydroxyphenylacetic Acid - metabolism; Animals; Biological and medical sciences; Brain - metabolism; Brain Chemistry; Cerebral Cortex - chemistry; Cerebral Cortex - metabolism; Chromatography, High Pressure Liquid; Disease Models, Animal; Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes; Dogs; Dopamine; Dopamine - analysis; Dopamine - metabolism; Hippocampus - chemistry; Hippocampus - metabolism; Histamine; Histamine - analysis; Histamine - metabolism; Hydroxyindoleacetic Acid - analysis; Hydroxyindoleacetic Acid - metabolism; Hypocretin; Medical sciences; Mutation; Narcolepsy; Narcolepsy - genetics; Narcolepsy - metabolism; Nervous system (semeiology, syndromes); Neurology; Norepinephrine; Norepinephrine - analysis; Norepinephrine - metabolism; Orexin; Orexin Receptors; Receptors, G-Protein-Coupled; Receptors, Neuropeptide - genetics; Serotonin - analysis; Serotonin - metabolism; Thalamus - chemistry; Thalamus - metabolism; Histamine; Narcolepsy; Norepinephrine; Dopamine; Hypocretin; Orexin; Fissipedia; Carnivora; Nervous system diseases; Central nervous system; Sleep disorder; Catecholamine; Vertebrata; Mammalia; Animal; Neurotransmitter; Peptidergic receptor; Mutation; Neurological disorder; Dog; Brain (vertebrata)
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(01)02270-4

A growing amount of evidence suggests that a deficiency in hypocretin/orexin neurotransmission is critically involved in animal and human forms of narcolepsy. Since hypocretin-containing neurons innervate and excite histaminergic tuberomammillary neurons, altered histaminergic neurotransmission may also be involved in narcolepsy. We found a significant decrease in histamine content in the cortex and thalamus, two structures important for histamine-mediated cortical arousal, in Hcrtr-2 mutated narcoleptic Dobermans. In contrast, dopamine and norepinephrine contents in these structures were elevated in narcoleptic animals, a finding consistent with our hypothesis of altered catecholaminergic transmission in these animals. Considering the fact that histamine promotes wakefulness, decreases in histaminergic neurotransmission may also account for the sleep abnormalities in hypocretin-deficient narcolepsy.