Upregulation of TRESK Channels Contributes to Motor and Sensory Recovery after Spinal Cord Injury
TWIK (tandem-pore domain weak inward rectifying K<sup>+</sup>)-related spinal cord K<sup>+</sup> channel (TRESK), a member of the two-pore domain K<sup>+</sup> channel family, is abundantly expressed in dorsal root ganglion (DRG) neurons. It is well documented tha...
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/8997 |
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| author | Gyu-Tae Kim Adrian S. Siregar Eun-Jin Kim Eun-Shin Lee Marie Merci Nyiramana Min Seok Woo Young-Sool Hah Jaehee Han Dawon Kang |
| author_facet | Gyu-Tae Kim Adrian S. Siregar Eun-Jin Kim Eun-Shin Lee Marie Merci Nyiramana Min Seok Woo Young-Sool Hah Jaehee Han Dawon Kang |
| author_sort | Gyu-Tae Kim |
| collection | DOAJ |
| description | TWIK (tandem-pore domain weak inward rectifying K<sup>+</sup>)-related spinal cord K<sup>+</sup> channel (TRESK), a member of the two-pore domain K<sup>+</sup> channel family, is abundantly expressed in dorsal root ganglion (DRG) neurons. It is well documented that TRESK expression is changed in several models of peripheral nerve injury, resulting in a shift in sensory neuron excitability. However, the role of TRESK in the model of spinal cord injury (SCI) has not been fully understood. This study investigates the role of TRESK in a thoracic spinal cord contusion model, and in transgenic mice overexpressed with the TRESK gene (TG<sub>TRESK</sub>). Immunostaining analysis showed that TRESK was expressed in the dorsal and ventral neurons of the spinal cord. The TRESK expression was increased by SCI in both dorsal and ventral neurons. TRESK mRNA expression was upregulated in the spinal cord and DRG isolated from the ninth thoracic (T9) spinal cord contusion rats. The expression was significantly upregulated in the spinal cord below the injury site at acute time points (6, 24, and 48 h) after SCI (<i>p</i> < 0.05). In addition, TRESK expression was markedly increased in DRGs below and adjacent to the injury site. TRESK was expressed in inflammatory cells. In addition, the number and fluorescence intensity of TRESK-positive neurons increased in the dorsal and ventral horns of the spinal cord after SCI. TG<sub>TRESK</sub> SCI mice showed faster paralysis recovery and higher mechanical threshold compared to wild-type (WT)-SCI mice. TG<sub>TRESK</sub> mice showed lower TNF-α concentrations in the blood than WT mice. In addition, IL-1β concentration and apoptotic signals in the caudal spinal cord and DRG were significantly decreased in TG<sub>TRESK</sub> SCI mice compared to WT-SCI mice (<i>p</i> < 0.05). These results indicate that TRESK upregulated following SCI contributes to the recovery of paralysis and mechanical pain threshold by suppressing the excitability of motor and sensory neurons and inflammatory and apoptotic processes. |
| first_indexed | 2024-03-10T14:32:04Z |
| format | Article |
| id | doaj.art-6564d907b6d64389936ea19ccc29b6cc |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:32:04Z |
| publishDate | 2020-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6564d907b6d64389936ea19ccc29b6cc2023-11-20T22:30:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123899710.3390/ijms21238997Upregulation of TRESK Channels Contributes to Motor and Sensory Recovery after Spinal Cord InjuryGyu-Tae Kim0Adrian S. Siregar1Eun-Jin Kim2Eun-Shin Lee3Marie Merci Nyiramana4Min Seok Woo5Young-Sool Hah6Jaehee Han7Dawon Kang8Department of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Rehabilitation Medicine, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaBiomedical Research Institute, Gyeongsang National University Hospital, Jinju 52727, KoreaDepartment of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaTWIK (tandem-pore domain weak inward rectifying K<sup>+</sup>)-related spinal cord K<sup>+</sup> channel (TRESK), a member of the two-pore domain K<sup>+</sup> channel family, is abundantly expressed in dorsal root ganglion (DRG) neurons. It is well documented that TRESK expression is changed in several models of peripheral nerve injury, resulting in a shift in sensory neuron excitability. However, the role of TRESK in the model of spinal cord injury (SCI) has not been fully understood. This study investigates the role of TRESK in a thoracic spinal cord contusion model, and in transgenic mice overexpressed with the TRESK gene (TG<sub>TRESK</sub>). Immunostaining analysis showed that TRESK was expressed in the dorsal and ventral neurons of the spinal cord. The TRESK expression was increased by SCI in both dorsal and ventral neurons. TRESK mRNA expression was upregulated in the spinal cord and DRG isolated from the ninth thoracic (T9) spinal cord contusion rats. The expression was significantly upregulated in the spinal cord below the injury site at acute time points (6, 24, and 48 h) after SCI (<i>p</i> < 0.05). In addition, TRESK expression was markedly increased in DRGs below and adjacent to the injury site. TRESK was expressed in inflammatory cells. In addition, the number and fluorescence intensity of TRESK-positive neurons increased in the dorsal and ventral horns of the spinal cord after SCI. TG<sub>TRESK</sub> SCI mice showed faster paralysis recovery and higher mechanical threshold compared to wild-type (WT)-SCI mice. TG<sub>TRESK</sub> mice showed lower TNF-α concentrations in the blood than WT mice. In addition, IL-1β concentration and apoptotic signals in the caudal spinal cord and DRG were significantly decreased in TG<sub>TRESK</sub> SCI mice compared to WT-SCI mice (<i>p</i> < 0.05). These results indicate that TRESK upregulated following SCI contributes to the recovery of paralysis and mechanical pain threshold by suppressing the excitability of motor and sensory neurons and inflammatory and apoptotic processes.https://www.mdpi.com/1422-0067/21/23/8997dorsal root ganglioninflammationoxidative stressspinal cord injuriestwo-pore domain K<sup>+</sup> channel |
| spellingShingle | Gyu-Tae Kim Adrian S. Siregar Eun-Jin Kim Eun-Shin Lee Marie Merci Nyiramana Min Seok Woo Young-Sool Hah Jaehee Han Dawon Kang Upregulation of TRESK Channels Contributes to Motor and Sensory Recovery after Spinal Cord Injury International Journal of Molecular Sciences dorsal root ganglion inflammation oxidative stress spinal cord injuries two-pore domain K<sup>+</sup> channel |
| title | Upregulation of TRESK Channels Contributes to Motor and Sensory Recovery after Spinal Cord Injury |
| title_full | Upregulation of TRESK Channels Contributes to Motor and Sensory Recovery after Spinal Cord Injury |
| title_fullStr | Upregulation of TRESK Channels Contributes to Motor and Sensory Recovery after Spinal Cord Injury |
| title_full_unstemmed | Upregulation of TRESK Channels Contributes to Motor and Sensory Recovery after Spinal Cord Injury |
| title_short | Upregulation of TRESK Channels Contributes to Motor and Sensory Recovery after Spinal Cord Injury |
| title_sort | upregulation of tresk channels contributes to motor and sensory recovery after spinal cord injury |
| topic | dorsal root ganglion inflammation oxidative stress spinal cord injuries two-pore domain K<sup>+</sup> channel |
| url | https://www.mdpi.com/1422-0067/21/23/8997 |
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