Neuropeptide Y in the medial habenula alleviates migraine-like behaviors through the Y1 receptor
Abstract Background Migraine is a highly disabling health burden with multiple symptoms; however, it remains undertreated because of an inadequate understanding of its neural mechanisms. Neuropeptide Y (NPY) has been demonstrated to be involved in the modulation of pain and emotion, and may play a r...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10194-023-01596-z |
| _version_ | 1797817853866409984 |
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| author | Chunxiao Yang Zihua Gong Xiaochen Zhang Shuai Miao Bozhi Li Wei Xie Tao Wang Xun Han Liang Wang Zhao Dong Shengyuan Yu |
| author_facet | Chunxiao Yang Zihua Gong Xiaochen Zhang Shuai Miao Bozhi Li Wei Xie Tao Wang Xun Han Liang Wang Zhao Dong Shengyuan Yu |
| author_sort | Chunxiao Yang |
| collection | DOAJ |
| description | Abstract Background Migraine is a highly disabling health burden with multiple symptoms; however, it remains undertreated because of an inadequate understanding of its neural mechanisms. Neuropeptide Y (NPY) has been demonstrated to be involved in the modulation of pain and emotion, and may play a role in migraine pathophysiology. Changes in NPY levels have been found in patients with migraine, but whether and how these changes contribute to migraine is unknown. Therefore, the purpose of this study was to investigate the role of NPY in migraine-like phenotypes. Methods Here, we used intraperitoneal injection of glyceryl trinitrate (GTN, 10 mg/kg) as a migraine mouse model, which was verified by light-aversive test, von Frey test, and elevated plus maze test. We then performed whole-brain imaging with NPY-GFP mice to explore the critical regions where NPY was changed by GTN treatment. Next, we microinjected NPY into the medial habenula (MHb), and further infused Y1 or Y2 receptor agonists into the MHb, respectively, to detect the effects of NPY in GTN-induced migraine-like behaviors. Results GTN effectively triggered allodynia, photophobia, and anxiety-like behaviors in mice. After that, we found a decreased level of GFP+ cells in the MHb of GTN-treated mice. Microinjection of NPY attenuated GTN-induced allodynia and anxiety without affecting photophobia. Furthermore, we found that activation of Y1—but not Y2—receptors attenuated GTN-induced allodynia and anxiety. Conclusions Taken together, our data support that the NPY signaling in the MHb produces analgesic and anxiolytic effects through the Y1 receptor. These findings may provide new insights into novel therapeutic targets for the treatment of migraine. Graphical Abstract |
| first_indexed | 2024-03-13T08:59:34Z |
| format | Article |
| id | doaj.art-91ffefd6526b494cbc5e2fb55b6fec70 |
| institution | Directory Open Access Journal |
| issn | 1129-2377 |
| language | English |
| last_indexed | 2024-03-13T08:59:34Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-91ffefd6526b494cbc5e2fb55b6fec702023-05-28T11:23:16ZengBMCThe Journal of Headache and Pain1129-23772023-05-0124112010.1186/s10194-023-01596-zNeuropeptide Y in the medial habenula alleviates migraine-like behaviors through the Y1 receptorChunxiao Yang0Zihua Gong1Xiaochen Zhang2Shuai Miao3Bozhi Li4Wei Xie5Tao Wang6Xun Han7Liang Wang8Zhao Dong9Shengyuan Yu10School of Medicine, Nankai UniversityDepartment of Neurology, the First Medical Center, Chinese PLA General HospitalAcademy of Medical Engineering and Translational Medicine, Tianjin UniversityDepartment of Neurology, the First Medical Center, Chinese PLA General HospitalDepartment of Neurology, the First Medical Center, Chinese PLA General HospitalDepartment of Neurology, the First Medical Center, Chinese PLA General HospitalDepartment of Neurology, the First Medical Center, Chinese PLA General HospitalDepartment of Neurology, the First Medical Center, Chinese PLA General HospitalInstitute of Neuroscience, Zhejiang University School of MedicineSchool of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversityAbstract Background Migraine is a highly disabling health burden with multiple symptoms; however, it remains undertreated because of an inadequate understanding of its neural mechanisms. Neuropeptide Y (NPY) has been demonstrated to be involved in the modulation of pain and emotion, and may play a role in migraine pathophysiology. Changes in NPY levels have been found in patients with migraine, but whether and how these changes contribute to migraine is unknown. Therefore, the purpose of this study was to investigate the role of NPY in migraine-like phenotypes. Methods Here, we used intraperitoneal injection of glyceryl trinitrate (GTN, 10 mg/kg) as a migraine mouse model, which was verified by light-aversive test, von Frey test, and elevated plus maze test. We then performed whole-brain imaging with NPY-GFP mice to explore the critical regions where NPY was changed by GTN treatment. Next, we microinjected NPY into the medial habenula (MHb), and further infused Y1 or Y2 receptor agonists into the MHb, respectively, to detect the effects of NPY in GTN-induced migraine-like behaviors. Results GTN effectively triggered allodynia, photophobia, and anxiety-like behaviors in mice. After that, we found a decreased level of GFP+ cells in the MHb of GTN-treated mice. Microinjection of NPY attenuated GTN-induced allodynia and anxiety without affecting photophobia. Furthermore, we found that activation of Y1—but not Y2—receptors attenuated GTN-induced allodynia and anxiety. Conclusions Taken together, our data support that the NPY signaling in the MHb produces analgesic and anxiolytic effects through the Y1 receptor. These findings may provide new insights into novel therapeutic targets for the treatment of migraine. Graphical Abstracthttps://doi.org/10.1186/s10194-023-01596-zMigraineGlyceryl trinitrateNeuropeptide YY1 receptorMedial habenula |
| spellingShingle | Chunxiao Yang Zihua Gong Xiaochen Zhang Shuai Miao Bozhi Li Wei Xie Tao Wang Xun Han Liang Wang Zhao Dong Shengyuan Yu Neuropeptide Y in the medial habenula alleviates migraine-like behaviors through the Y1 receptor The Journal of Headache and Pain Migraine Glyceryl trinitrate Neuropeptide Y Y1 receptor Medial habenula |
| title | Neuropeptide Y in the medial habenula alleviates migraine-like behaviors through the Y1 receptor |
| title_full | Neuropeptide Y in the medial habenula alleviates migraine-like behaviors through the Y1 receptor |
| title_fullStr | Neuropeptide Y in the medial habenula alleviates migraine-like behaviors through the Y1 receptor |
| title_full_unstemmed | Neuropeptide Y in the medial habenula alleviates migraine-like behaviors through the Y1 receptor |
| title_short | Neuropeptide Y in the medial habenula alleviates migraine-like behaviors through the Y1 receptor |
| title_sort | neuropeptide y in the medial habenula alleviates migraine like behaviors through the y1 receptor |
| topic | Migraine Glyceryl trinitrate Neuropeptide Y Y1 receptor Medial habenula |
| url | https://doi.org/10.1186/s10194-023-01596-z |
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