Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage
Subarachnoid hemorrhage (SAH) is a devastating form of stroke, which poses a series of intractable challenges to clinical practice. Imbalance of mitochondrial homeostasis has been thought to be the crucial pathomechanism in early brain injury (EBI) cascade after SAH. Irisin, a protein related to met...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.640215/full |
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| author | Tianqi Tu Shigang Yin Shigang Yin Jinwei Pang Jinwei Pang Jinwei Pang Xianhui Zhang Lifang Zhang Yuxuan Zhang Yuke Xie Kecheng Guo Ligang Chen Ligang Chen Ligang Chen Jianhua Peng Jianhua Peng Jianhua Peng Yong Jiang Yong Jiang Yong Jiang Yong Jiang |
| author_facet | Tianqi Tu Shigang Yin Shigang Yin Jinwei Pang Jinwei Pang Jinwei Pang Xianhui Zhang Lifang Zhang Yuxuan Zhang Yuke Xie Kecheng Guo Ligang Chen Ligang Chen Ligang Chen Jianhua Peng Jianhua Peng Jianhua Peng Yong Jiang Yong Jiang Yong Jiang Yong Jiang |
| author_sort | Tianqi Tu |
| collection | DOAJ |
| description | Subarachnoid hemorrhage (SAH) is a devastating form of stroke, which poses a series of intractable challenges to clinical practice. Imbalance of mitochondrial homeostasis has been thought to be the crucial pathomechanism in early brain injury (EBI) cascade after SAH. Irisin, a protein related to metabolism and mitochondrial homeostasis, has been reported to play pivotal roles in post-stroke neuroprotection. However, whether this myokine can exert neuroprotection effects after SAH remains unknown. In the present study, we explored the protective effects of irisin and the underlying mechanisms related to mitochondrial biogenesis in a SAH animal model. Endovascular perforation was used to induce SAH, and recombinant irisin was administered intracerebroventricularly. Neurobehavioral assessments, TdT-UTP nick end labeling (TUNEL) staining, dihydroethidium (DHE) staining, immunofluorescence, western blot, and transmission electron microscopy (TEM) were performed for post-SAH assessments. We demonstrated that irisin treatment improved neurobehavioral scores, reduced neuronal apoptosis, and alleviated oxidative stress in EBI after SAH. More importantly, the administration of exogenous irisin conserved the mitochondrial morphology and promoted mitochondrial biogenesis. The protective effects of irisin were partially reversed by the mitochondrial uncoupling protein-2 (UCP-2) inhibitor. Taken together, irisin may have neuroprotective effects against SAH via improving the mitochondrial biogenesis, at least in part, through UCP-2 related targets. |
| first_indexed | 2024-12-19T11:20:56Z |
| format | Article |
| id | doaj.art-f35e62a3f98247bb8784272fa82564c1 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-19T11:20:56Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-f35e62a3f98247bb8784272fa82564c12022-12-21T20:23:49ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-02-011310.3389/fnagi.2021.640215640215Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid HemorrhageTianqi Tu0Shigang Yin1Shigang Yin2Jinwei Pang3Jinwei Pang4Jinwei Pang5Xianhui Zhang6Lifang Zhang7Yuxuan Zhang8Yuke Xie9Kecheng Guo10Ligang Chen11Ligang Chen12Ligang Chen13Jianhua Peng14Jianhua Peng15Jianhua Peng16Yong Jiang17Yong Jiang18Yong Jiang19Yong Jiang20Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaLuzhou Key Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaSichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaSichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaSichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaLuzhou Key Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaLuzhou Key Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaSichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaLuzhou Key Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaSichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaLuzhou Key Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaSichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaSubarachnoid hemorrhage (SAH) is a devastating form of stroke, which poses a series of intractable challenges to clinical practice. Imbalance of mitochondrial homeostasis has been thought to be the crucial pathomechanism in early brain injury (EBI) cascade after SAH. Irisin, a protein related to metabolism and mitochondrial homeostasis, has been reported to play pivotal roles in post-stroke neuroprotection. However, whether this myokine can exert neuroprotection effects after SAH remains unknown. In the present study, we explored the protective effects of irisin and the underlying mechanisms related to mitochondrial biogenesis in a SAH animal model. Endovascular perforation was used to induce SAH, and recombinant irisin was administered intracerebroventricularly. Neurobehavioral assessments, TdT-UTP nick end labeling (TUNEL) staining, dihydroethidium (DHE) staining, immunofluorescence, western blot, and transmission electron microscopy (TEM) were performed for post-SAH assessments. We demonstrated that irisin treatment improved neurobehavioral scores, reduced neuronal apoptosis, and alleviated oxidative stress in EBI after SAH. More importantly, the administration of exogenous irisin conserved the mitochondrial morphology and promoted mitochondrial biogenesis. The protective effects of irisin were partially reversed by the mitochondrial uncoupling protein-2 (UCP-2) inhibitor. Taken together, irisin may have neuroprotective effects against SAH via improving the mitochondrial biogenesis, at least in part, through UCP-2 related targets.https://www.frontiersin.org/articles/10.3389/fnagi.2021.640215/fullFNDC5/irisinsubarachnoid hemorrhagemitochondrial homeostasisoxidative stressneuronal apoptosis |
| spellingShingle | Tianqi Tu Shigang Yin Shigang Yin Jinwei Pang Jinwei Pang Jinwei Pang Xianhui Zhang Lifang Zhang Yuxuan Zhang Yuke Xie Kecheng Guo Ligang Chen Ligang Chen Ligang Chen Jianhua Peng Jianhua Peng Jianhua Peng Yong Jiang Yong Jiang Yong Jiang Yong Jiang Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage Frontiers in Aging Neuroscience FNDC5/irisin subarachnoid hemorrhage mitochondrial homeostasis oxidative stress neuronal apoptosis |
| title | Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage |
| title_full | Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage |
| title_fullStr | Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage |
| title_full_unstemmed | Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage |
| title_short | Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage |
| title_sort | irisin contributes to neuroprotection by promoting mitochondrial biogenesis after experimental subarachnoid hemorrhage |
| topic | FNDC5/irisin subarachnoid hemorrhage mitochondrial homeostasis oxidative stress neuronal apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.640215/full |
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