Hypocretin Levels in Sporadic and Familial Cases of Canine Narcolepsy
Familial and sporadic forms of narcolepsy exist in both humans and canines. Mutations in the hypocretin receptor 2 gene (Hcrtr 2) cause canine familial narcolepsy. In humans, mutations in hypocretin-related genes are rare, but cerebrospinal fluid (CSF) hypocretin-1 is undetectable in most sporadic c...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2001-06-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996101903894 |
| _version_ | 1818721220265246720 |
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| author | Beth Ripley Nobuhiro Fujiki Mutsumi Okura Emmanuel Mignot Seiji Nishino |
| author_facet | Beth Ripley Nobuhiro Fujiki Mutsumi Okura Emmanuel Mignot Seiji Nishino |
| author_sort | Beth Ripley |
| collection | DOAJ |
| description | Familial and sporadic forms of narcolepsy exist in both humans and canines. Mutations in the hypocretin receptor 2 gene (Hcrtr 2) cause canine familial narcolepsy. In humans, mutations in hypocretin-related genes are rare, but cerebrospinal fluid (CSF) hypocretin-1 is undetectable in most sporadic cases. Using the canine model, we investigated (1) whether hypocretin deficiency is involved in sporadic cases and (2) whether alterations in hypocretin neurons or ligand levels also contribute to the phenotype in Hcrtr 2 mutants. We found that hypocretins were undetectable in the brains of three of three and the CSF of two of two sporadic narcoleptic dogs tested. In contrast, hypocretin levels were not altered in brains and CSF of genetically narcoleptic Dobermans, and hypocretin-containing neurons were of normal appearance. Therefore, multiple hypocretin-related etiologies are likely to be involved in canine narcolepsy. The presence of hypocretin peptides in Hcrtr 2-mutated animals suggests that neurotransmission through Hcrtr 1 may be intact, arguing for a preferential importance of Hcrtr 2-mediated function in narcolepsy. |
| first_indexed | 2024-12-17T20:35:16Z |
| format | Article |
| id | doaj.art-e2728d97b74c4ec4915640f4201106fc |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T20:35:16Z |
| publishDate | 2001-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-e2728d97b74c4ec4915640f4201106fc2022-12-21T21:33:28ZengElsevierNeurobiology of Disease1095-953X2001-06-0183525534Hypocretin Levels in Sporadic and Familial Cases of Canine NarcolepsyBeth Ripley0Nobuhiro Fujiki1Mutsumi Okura2Emmanuel Mignot3Seiji Nishino4Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, Palo Alto, California, 94304Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, Palo Alto, California, 94304Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, Palo Alto, California, 94304Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, Palo Alto, California, 94304Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, Palo Alto, California, 94304Familial and sporadic forms of narcolepsy exist in both humans and canines. Mutations in the hypocretin receptor 2 gene (Hcrtr 2) cause canine familial narcolepsy. In humans, mutations in hypocretin-related genes are rare, but cerebrospinal fluid (CSF) hypocretin-1 is undetectable in most sporadic cases. Using the canine model, we investigated (1) whether hypocretin deficiency is involved in sporadic cases and (2) whether alterations in hypocretin neurons or ligand levels also contribute to the phenotype in Hcrtr 2 mutants. We found that hypocretins were undetectable in the brains of three of three and the CSF of two of two sporadic narcoleptic dogs tested. In contrast, hypocretin levels were not altered in brains and CSF of genetically narcoleptic Dobermans, and hypocretin-containing neurons were of normal appearance. Therefore, multiple hypocretin-related etiologies are likely to be involved in canine narcolepsy. The presence of hypocretin peptides in Hcrtr 2-mutated animals suggests that neurotransmission through Hcrtr 1 may be intact, arguing for a preferential importance of Hcrtr 2-mediated function in narcolepsy.http://www.sciencedirect.com/science/article/pii/S0969996101903894hypocretinorexinnarcolepsyCSFradioimmunoassayimmunohistochemistry |
| spellingShingle | Beth Ripley Nobuhiro Fujiki Mutsumi Okura Emmanuel Mignot Seiji Nishino Hypocretin Levels in Sporadic and Familial Cases of Canine Narcolepsy Neurobiology of Disease hypocretin orexin narcolepsy CSF radioimmunoassay immunohistochemistry |
| title | Hypocretin Levels in Sporadic and Familial Cases of Canine Narcolepsy |
| title_full | Hypocretin Levels in Sporadic and Familial Cases of Canine Narcolepsy |
| title_fullStr | Hypocretin Levels in Sporadic and Familial Cases of Canine Narcolepsy |
| title_full_unstemmed | Hypocretin Levels in Sporadic and Familial Cases of Canine Narcolepsy |
| title_short | Hypocretin Levels in Sporadic and Familial Cases of Canine Narcolepsy |
| title_sort | hypocretin levels in sporadic and familial cases of canine narcolepsy |
| topic | hypocretin orexin narcolepsy CSF radioimmunoassay immunohistochemistry |
| url | http://www.sciencedirect.com/science/article/pii/S0969996101903894 |
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