Evaluation of transcriptomic changes after photobiomodulation in spinal cord injury

Abstract Spinal cord injury (SCI) is a significant cause of lifelong disability, with no available disease-modifying treatments to promote neuroprotection and axon regeneration after injury. Photobiomodulation (PBM) is a promising therapy which has proven effective at restoring lost function after S...

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Main Authors: Andrew R. Stevens, Mohammed Hadis, Hannah Alldrit, Michael R. Milward, Valentina Di Pietro, Deena M. A. Gendoo, Antonio Belli, William Palin, David J. Davies, Zubair Ahmed
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87300-4
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author Andrew R. Stevens
Mohammed Hadis
Hannah Alldrit
Michael R. Milward
Valentina Di Pietro
Deena M. A. Gendoo
Antonio Belli
William Palin
David J. Davies
Zubair Ahmed
author_facet Andrew R. Stevens
Mohammed Hadis
Hannah Alldrit
Michael R. Milward
Valentina Di Pietro
Deena M. A. Gendoo
Antonio Belli
William Palin
David J. Davies
Zubair Ahmed
author_sort Andrew R. Stevens
collection DOAJ
description Abstract Spinal cord injury (SCI) is a significant cause of lifelong disability, with no available disease-modifying treatments to promote neuroprotection and axon regeneration after injury. Photobiomodulation (PBM) is a promising therapy which has proven effective at restoring lost function after SCI in pre-clinical models. However, the precise mechanism of action is yet to be determined. Here, we used an in-vivo model of SCI in adult rats that received daily PBM (660 nm, 24 mW/cm2, 1 min) and at three days post-injury, the injured spinal cord segment was harvested and subjected to whole transcriptome sequencing and subsequent pathway analysis (generally applicable gene-set enrichment (GAGE)). Pathway analysis demonstrated 1275 differentially expressed genes (DEGs) after PBM treatment, of which 397 were upregulated and 878 were downregulated. Key pathways were significantly enriched, including 8.6-fold enrichment of “neuron projection morphogenesis” (adjusted p = 8.10 × 10− 14), with upregulation of Notch3, Slit1/Robo2 and Sema3g pathways. Ribosomal and oxidative phosphorylation pathways and NADH dehydrogenase were downregulated, and there was upregulation of ATP-dependent activity, cAMP and calcium signalling pathways. Key genes in apoptotic pathways were downregulated, as were S100 and cyclo-oxygenase components. Together, our study supports the favourable effects of PBM in promoting neuroregeneration and suppressing apoptosis after neurological injury. Further findings from pathway analysis suggest that downregulation of metabolism-associated pathways is a mechanism by which acute post-injury mitochondrial dysfunction may be averted by PBM therapy.
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spelling doaj-art-172575c1b477413fb39cb2cb8eb61d9b2025-01-26T12:27:55ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-87300-4Evaluation of transcriptomic changes after photobiomodulation in spinal cord injuryAndrew R. Stevens0Mohammed Hadis1Hannah Alldrit2Michael R. Milward3Valentina Di Pietro4Deena M. A. Gendoo5Antonio Belli6William Palin7David J. Davies8Zubair Ahmed9Neuroscience and Ophthalmology, Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of BirminghamPhototherapy Research Group, School of Dentistry, College of Medicine and Health, University of BirminghamDepartment of Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of BirminghamSchool of Dentistry, College of Medicine and Health, University of BirminghamNeuroscience and Ophthalmology, Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of BirminghamDepartment of Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of BirminghamNeuroscience and Ophthalmology, Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of BirminghamPhototherapy Research Group, School of Dentistry, College of Medicine and Health, University of BirminghamNeuroscience and Ophthalmology, Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of BirminghamNeuroscience and Ophthalmology, Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of BirminghamAbstract Spinal cord injury (SCI) is a significant cause of lifelong disability, with no available disease-modifying treatments to promote neuroprotection and axon regeneration after injury. Photobiomodulation (PBM) is a promising therapy which has proven effective at restoring lost function after SCI in pre-clinical models. However, the precise mechanism of action is yet to be determined. Here, we used an in-vivo model of SCI in adult rats that received daily PBM (660 nm, 24 mW/cm2, 1 min) and at three days post-injury, the injured spinal cord segment was harvested and subjected to whole transcriptome sequencing and subsequent pathway analysis (generally applicable gene-set enrichment (GAGE)). Pathway analysis demonstrated 1275 differentially expressed genes (DEGs) after PBM treatment, of which 397 were upregulated and 878 were downregulated. Key pathways were significantly enriched, including 8.6-fold enrichment of “neuron projection morphogenesis” (adjusted p = 8.10 × 10− 14), with upregulation of Notch3, Slit1/Robo2 and Sema3g pathways. Ribosomal and oxidative phosphorylation pathways and NADH dehydrogenase were downregulated, and there was upregulation of ATP-dependent activity, cAMP and calcium signalling pathways. Key genes in apoptotic pathways were downregulated, as were S100 and cyclo-oxygenase components. Together, our study supports the favourable effects of PBM in promoting neuroregeneration and suppressing apoptosis after neurological injury. Further findings from pathway analysis suggest that downregulation of metabolism-associated pathways is a mechanism by which acute post-injury mitochondrial dysfunction may be averted by PBM therapy.https://doi.org/10.1038/s41598-025-87300-4PhotobiomodulationSpinal cord injuryLow-level laser therapyNeurotraumaNeuroprotectionNeuroregeneration
spellingShingle Andrew R. Stevens
Mohammed Hadis
Hannah Alldrit
Michael R. Milward
Valentina Di Pietro
Deena M. A. Gendoo
Antonio Belli
William Palin
David J. Davies
Zubair Ahmed
Evaluation of transcriptomic changes after photobiomodulation in spinal cord injury
Scientific Reports
Photobiomodulation
Spinal cord injury
Low-level laser therapy
Neurotrauma
Neuroprotection
Neuroregeneration
title Evaluation of transcriptomic changes after photobiomodulation in spinal cord injury
title_full Evaluation of transcriptomic changes after photobiomodulation in spinal cord injury
title_fullStr Evaluation of transcriptomic changes after photobiomodulation in spinal cord injury
title_full_unstemmed Evaluation of transcriptomic changes after photobiomodulation in spinal cord injury
title_short Evaluation of transcriptomic changes after photobiomodulation in spinal cord injury
title_sort evaluation of transcriptomic changes after photobiomodulation in spinal cord injury
topic Photobiomodulation
Spinal cord injury
Low-level laser therapy
Neurotrauma
Neuroprotection
Neuroregeneration
url https://doi.org/10.1038/s41598-025-87300-4
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