The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brain
Hypocretin (Hcrtr, HCRTR) / orexin (OX) receptors modulate a range of neurobiological functions and are drug targets for several disorders. Mapping the distribution of receptors in the brain can inform their function and guide targeting of specific disorders. Although studied in rodents, orexin rece...
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Elsevier
2024-12-01
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| Series: | Medicine in Drug Discovery |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590098624000277 |
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| author | Sanjida Mir Ryan J. Keenan Romke Bron Cameron J. Nowell Catriona McLean Leah C. Beauchamp Laura J. Vella Brian Dean Daniel Hoyer Laura H. Jacobson |
| author_facet | Sanjida Mir Ryan J. Keenan Romke Bron Cameron J. Nowell Catriona McLean Leah C. Beauchamp Laura J. Vella Brian Dean Daniel Hoyer Laura H. Jacobson |
| author_sort | Sanjida Mir |
| collection | DOAJ |
| description | Hypocretin (Hcrtr, HCRTR) / orexin (OX) receptors modulate a range of neurobiological functions and are drug targets for several disorders. Mapping the distribution of receptors in the brain can inform their function and guide targeting of specific disorders. Although studied in rodents, orexin receptor distribution has remained relatively unexplored in humans, and thus there is also a paucity of comparative anatomy. The aim of this study was therefore to map the distribution of hypocretin/orexin receptor mRNA in selected regions of the mouse and human brain by non-radioactive in situ hybridization (ISH) using digoxigenin (DIG)-labelled cRNA anti-sense probes. Data revealed both distinct and overlapping patterns of distributions of Hcrtr1/HCRTR1 and Hcrtr2/HCRTR2 mRNA suggesting that the functions of the orexin system are mediated differently by each receptor. In the mouse brain, the highest expression of Hcrtr1 mRNA was in the locus coeruleus (LC) whereas Hcrtr2 mRNA was most abundant in the lateral hypothalamus (LH). The human caudate nuclei showed significant expression of both HCRTR1 and HCRTR2 mRNA, whereas the mouse predominantly expressed Hcrtr2 mRNA. The noradrenergic neurons of the human LC showed high signals for both HCRTR1 (71.7%) and HCRTR2 (81.5%) mRNA. Expression of HCRTR2 mRNA in non-noradrenergic human LC cells was also notable. The distribution pattern in mouse and human brains is consistent with the involvement of the orexin system in arousal and the sleep/wake cycle in both species, however, variations in receptor subtype expression profiles suggests that species differences in responses to orexin receptor ligands may be expected. |
| format | Article |
| id | doaj-art-9f4c6bbb7e4a49a9a8786c108d2f560f |
| institution | Kabale University |
| issn | 2590-0986 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Medicine in Drug Discovery |
| spelling | doaj-art-9f4c6bbb7e4a49a9a8786c108d2f560f2024-11-22T07:38:49ZengElsevierMedicine in Drug Discovery2590-09862024-12-0124100202The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brainSanjida Mir0Ryan J. Keenan1Romke Bron2Cameron J. Nowell3Catriona McLean4Leah C. Beauchamp5Laura J. Vella6Brian Dean7Daniel Hoyer8Laura H. Jacobson9Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Victoria, AustraliaDepartment of Biochemistry and Pharmacology, University of Melbourne, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, AustraliaDrug Discovery Biology, Monash Institutes of Pharmaceutical Sciences, Monash University, Parkville, Victoria, AustraliaDrug Discovery Biology, Monash Institutes of Pharmaceutical Sciences, Monash University, Parkville, Victoria, AustraliaVictorian Brain Bank, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Pathology, The Alfred, Melbourne, Victoria, AustraliaThe Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, AustraliaThe Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, AustraliaThe Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, AustraliaDepartment of Biochemistry and Pharmacology, University of Melbourne, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA; Corresponding authors at: Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Corresponding authors at: Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.Hypocretin (Hcrtr, HCRTR) / orexin (OX) receptors modulate a range of neurobiological functions and are drug targets for several disorders. Mapping the distribution of receptors in the brain can inform their function and guide targeting of specific disorders. Although studied in rodents, orexin receptor distribution has remained relatively unexplored in humans, and thus there is also a paucity of comparative anatomy. The aim of this study was therefore to map the distribution of hypocretin/orexin receptor mRNA in selected regions of the mouse and human brain by non-radioactive in situ hybridization (ISH) using digoxigenin (DIG)-labelled cRNA anti-sense probes. Data revealed both distinct and overlapping patterns of distributions of Hcrtr1/HCRTR1 and Hcrtr2/HCRTR2 mRNA suggesting that the functions of the orexin system are mediated differently by each receptor. In the mouse brain, the highest expression of Hcrtr1 mRNA was in the locus coeruleus (LC) whereas Hcrtr2 mRNA was most abundant in the lateral hypothalamus (LH). The human caudate nuclei showed significant expression of both HCRTR1 and HCRTR2 mRNA, whereas the mouse predominantly expressed Hcrtr2 mRNA. The noradrenergic neurons of the human LC showed high signals for both HCRTR1 (71.7%) and HCRTR2 (81.5%) mRNA. Expression of HCRTR2 mRNA in non-noradrenergic human LC cells was also notable. The distribution pattern in mouse and human brains is consistent with the involvement of the orexin system in arousal and the sleep/wake cycle in both species, however, variations in receptor subtype expression profiles suggests that species differences in responses to orexin receptor ligands may be expected.http://www.sciencedirect.com/science/article/pii/S2590098624000277HypocretinOrexinhypocretin receptor mRNAOrexin receptorsIn situ hybridization |
| spellingShingle | Sanjida Mir Ryan J. Keenan Romke Bron Cameron J. Nowell Catriona McLean Leah C. Beauchamp Laura J. Vella Brian Dean Daniel Hoyer Laura H. Jacobson The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brain Medicine in Drug Discovery Hypocretin Orexin hypocretin receptor mRNA Orexin receptors In situ hybridization |
| title | The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brain |
| title_full | The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brain |
| title_fullStr | The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brain |
| title_full_unstemmed | The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brain |
| title_short | The distribution of Hypocretin/Orexin receptor mRNA in the mouse and human brain |
| title_sort | distribution of hypocretin orexin receptor mrna in the mouse and human brain |
| topic | Hypocretin Orexin hypocretin receptor mRNA Orexin receptors In situ hybridization |
| url | http://www.sciencedirect.com/science/article/pii/S2590098624000277 |
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