GABAB receptors regulate the neural stem cell potential of Pkd2l1+ cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway
Cerebrospinal fluid-contacting neurons (CSF-cNs) exhibit neural stem cell (NSC) properties both in vitro and in vivo, and they may play a critical role in recovery after spinal cord injury (SCI). GABAB receptors (GABABRs) are expressed in Pkd2l1+ CSF-cNs. However, their role in Pkd2l1+ CSF-cNs still...
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Elsevier
2025-02-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025000292 |
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| author | Liang Cao Wei-Hong Yan Wenjun Pi Yi Zhang Yan-Xiang Xiong V. Wee Yong Mengzhou Xue Qing Li Chunfu Zheng Leiluo Yang |
| author_facet | Liang Cao Wei-Hong Yan Wenjun Pi Yi Zhang Yan-Xiang Xiong V. Wee Yong Mengzhou Xue Qing Li Chunfu Zheng Leiluo Yang |
| author_sort | Liang Cao |
| collection | DOAJ |
| description | Cerebrospinal fluid-contacting neurons (CSF-cNs) exhibit neural stem cell (NSC) properties both in vitro and in vivo, and they may play a critical role in recovery after spinal cord injury (SCI). GABAB receptors (GABABRs) are expressed in Pkd2l1+ CSF-cNs. However, their role in Pkd2l1+ CSF-cNs still needs to be discovered. In this study, we observed a significant reduction in GABABR expression in a murine model 7 d after SCI. We further discovered that GABABR activation enhanced the proliferation of Pkd2l1+ CSF-cNs while inhibiting apoptosis. Additionally, this activation mitigated vacuole loss and neuronal damage in the pericentral canal region of the spinal cord, attenuated myelin and axonal loss within the spinal cord, and facilitated motor function recovery in SCI model mice. Mechanistically, GABABR primed quiescent Pkd2l1+ CSF-cNs for cell cycle reentry through the activation of PI3K/Akt signaling. Our findings suggest that GABABR activation enhances the NSC potential of Pkd2l1+ CSF-cNs, ultimately enabling post-SCI recovery in murine models. |
| format | Article |
| id | doaj-art-678325629b454ef28afe3906b2f02922 |
| institution | Kabale University |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-678325629b454ef28afe3906b2f029222025-02-07T04:46:45ZengElsevierBrain Research Bulletin1873-27472025-02-01221111217GABAB receptors regulate the neural stem cell potential of Pkd2l1+ cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathwayLiang Cao0Wei-Hong Yan1Wenjun Pi2Yi Zhang3Yan-Xiang Xiong4V. Wee Yong5Mengzhou Xue6Qing Li7Chunfu Zheng8Leiluo Yang9Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury, Zhengzhou, Henan, ChinaDepartment of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, ChinaDepartment of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, ChinaShunyi Maternal and Children's Hospital of Beijing Children's Hospital, Beijing, ChinaDepartment of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, ChinaHotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, CanadaDepartment of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury, Zhengzhou, Henan, ChinaDepartment of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; Corresponding authors.Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada; Corresponding authors.Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; Corresponding authors.Cerebrospinal fluid-contacting neurons (CSF-cNs) exhibit neural stem cell (NSC) properties both in vitro and in vivo, and they may play a critical role in recovery after spinal cord injury (SCI). GABAB receptors (GABABRs) are expressed in Pkd2l1+ CSF-cNs. However, their role in Pkd2l1+ CSF-cNs still needs to be discovered. In this study, we observed a significant reduction in GABABR expression in a murine model 7 d after SCI. We further discovered that GABABR activation enhanced the proliferation of Pkd2l1+ CSF-cNs while inhibiting apoptosis. Additionally, this activation mitigated vacuole loss and neuronal damage in the pericentral canal region of the spinal cord, attenuated myelin and axonal loss within the spinal cord, and facilitated motor function recovery in SCI model mice. Mechanistically, GABABR primed quiescent Pkd2l1+ CSF-cNs for cell cycle reentry through the activation of PI3K/Akt signaling. Our findings suggest that GABABR activation enhances the NSC potential of Pkd2l1+ CSF-cNs, ultimately enabling post-SCI recovery in murine models.http://www.sciencedirect.com/science/article/pii/S0361923025000292Spinal cord injuryPkd2l1Neural stem cellsGABAB receptorsCSF-cNsPI3K/Akt |
| spellingShingle | Liang Cao Wei-Hong Yan Wenjun Pi Yi Zhang Yan-Xiang Xiong V. Wee Yong Mengzhou Xue Qing Li Chunfu Zheng Leiluo Yang GABAB receptors regulate the neural stem cell potential of Pkd2l1+ cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway Brain Research Bulletin Spinal cord injury Pkd2l1 Neural stem cells GABAB receptors CSF-cNs PI3K/Akt |
| title | GABAB receptors regulate the neural stem cell potential of Pkd2l1+ cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway |
| title_full | GABAB receptors regulate the neural stem cell potential of Pkd2l1+ cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway |
| title_fullStr | GABAB receptors regulate the neural stem cell potential of Pkd2l1+ cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway |
| title_full_unstemmed | GABAB receptors regulate the neural stem cell potential of Pkd2l1+ cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway |
| title_short | GABAB receptors regulate the neural stem cell potential of Pkd2l1+ cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway |
| title_sort | gabab receptors regulate the neural stem cell potential of pkd2l1 cerebrospinal fluid contacting neurons via the pi3k akt signaling pathway |
| topic | Spinal cord injury Pkd2l1 Neural stem cells GABAB receptors CSF-cNs PI3K/Akt |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025000292 |
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