Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in mice
Abstract Background Deficient DNA repair and excessive DNA damage contribute to neurodegenerative disease. However, the role of DNA damage and repair in spinal cord injury (SCI) is unclear. SCI, a debilitating disruption of the structural and biological network of the spinal cord, is characterized b...
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BMC
2025-01-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | https://doi.org/10.1186/s12929-024-01104-8 |
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| author | Elle EM Scheijen Naomi Veeningen Sam Duwé Anna Ivanova Jana Van Broeckhoven Sven Hendrix David M Wilson |
| author_facet | Elle EM Scheijen Naomi Veeningen Sam Duwé Anna Ivanova Jana Van Broeckhoven Sven Hendrix David M Wilson |
| author_sort | Elle EM Scheijen |
| collection | DOAJ |
| description | Abstract Background Deficient DNA repair and excessive DNA damage contribute to neurodegenerative disease. However, the role of DNA damage and repair in spinal cord injury (SCI) is unclear. SCI, a debilitating disruption of the structural and biological network of the spinal cord, is characterized by oxidative stress. Nevertheless, the pathophysiological mechanisms leading to neuronal loss following SCI remain incompletely defined. Methods: Using a contusion model, a severe SCI was induced at the L1 spinal level in C57Bl/6J mice. The temporal and spatial presence of DNA damage was then determined via immunolabeling for the DNA damage marker, γH2AX, from 1 h post-injury (hpi) to 28 days post-injury (dpi). Results: Our analysis revealed that increased DNA damage foci were present from 1 hpi to 3 dpi in SCI mice relative to controls (sham surgery and naive), with the damage signal spreading over time longitudinally from the affected area to more rostral and caudal regions. Co-labeling of γH2AX with NeuN revealed neuronal specificity of DNA damage, with increased early cell death (pan-nuclear γH2AX) peaking at 1 dpi and apoptosis (cleaved Caspase-3) arising later at 3 dpi. Conclusion: Our study indicates a possible role of DNA damage in neuronal loss following SCI and highlights the need for early interventions targeting DNA repair to preserve neuronal tissue. |
| format | Article |
| id | doaj-art-81c8a843e8a34448a8f50f628dccfcfc |
| institution | Kabale University |
| issn | 1423-0127 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Journal of Biomedical Science |
| spelling | doaj-art-81c8a843e8a34448a8f50f628dccfcfc2025-01-26T12:46:17ZengBMCJournal of Biomedical Science1423-01272025-01-0132111610.1186/s12929-024-01104-8Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in miceElle EM Scheijen0Naomi Veeningen1Sam Duwé2Anna Ivanova3Jana Van Broeckhoven4Sven Hendrix5David M Wilson6Neurosciences, Biomedical Research Institute, Hasselt UniversityImmunology and Infection, Biomedical Research Institute, Hasselt UniversityAdvanced Optical Microscopy Centre, Biomedical Research Institute, Hasselt UniversityData Science Institute, Biomedical Research Institute, Hasselt UniversityImmunology and Infection, Biomedical Research Institute, Hasselt UniversityInstitute for Translational Medicine, Medical School HamburgNeurosciences, Biomedical Research Institute, Hasselt UniversityAbstract Background Deficient DNA repair and excessive DNA damage contribute to neurodegenerative disease. However, the role of DNA damage and repair in spinal cord injury (SCI) is unclear. SCI, a debilitating disruption of the structural and biological network of the spinal cord, is characterized by oxidative stress. Nevertheless, the pathophysiological mechanisms leading to neuronal loss following SCI remain incompletely defined. Methods: Using a contusion model, a severe SCI was induced at the L1 spinal level in C57Bl/6J mice. The temporal and spatial presence of DNA damage was then determined via immunolabeling for the DNA damage marker, γH2AX, from 1 h post-injury (hpi) to 28 days post-injury (dpi). Results: Our analysis revealed that increased DNA damage foci were present from 1 hpi to 3 dpi in SCI mice relative to controls (sham surgery and naive), with the damage signal spreading over time longitudinally from the affected area to more rostral and caudal regions. Co-labeling of γH2AX with NeuN revealed neuronal specificity of DNA damage, with increased early cell death (pan-nuclear γH2AX) peaking at 1 dpi and apoptosis (cleaved Caspase-3) arising later at 3 dpi. Conclusion: Our study indicates a possible role of DNA damage in neuronal loss following SCI and highlights the need for early interventions targeting DNA repair to preserve neuronal tissue.https://doi.org/10.1186/s12929-024-01104-8Spinal cord injuryDNA damageOxidative stressGamma-H2AXNeuronal deathDNA repair |
| spellingShingle | Elle EM Scheijen Naomi Veeningen Sam Duwé Anna Ivanova Jana Van Broeckhoven Sven Hendrix David M Wilson Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in mice Journal of Biomedical Science Spinal cord injury DNA damage Oxidative stress Gamma-H2AX Neuronal death DNA repair |
| title | Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in mice |
| title_full | Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in mice |
| title_fullStr | Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in mice |
| title_full_unstemmed | Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in mice |
| title_short | Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in mice |
| title_sort | temporal and spatial pattern of dna damage in neurons following spinal cord injury in mice |
| topic | Spinal cord injury DNA damage Oxidative stress Gamma-H2AX Neuronal death DNA repair |
| url | https://doi.org/10.1186/s12929-024-01104-8 |
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