Evaluation of transcriptomic changes after photobiomodulation in spinal cord injury
Stevens, Andrew R ; Hadis, Mohammed ; Alldrit, Hannah ; Milward, Michael R ; Di Pietro, Valentina ; Gendoo, Deena M A ; Belli, Antonio ; Palin, William ; Davies, David J ; Ahmed, Zubair
Stevens, Andrew R
Hadis, Mohammed
Alldrit, Hannah
Milward, Michael R
Di Pietro, Valentina
Gendoo, Deena M A
Belli, Antonio
Palin, William
Davies, David J
Ahmed, Zubair
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Publication date
2025-01-25
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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/cm, 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), 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.
Citation
Stevens AR, Hadis M, Alldrit H, Milward MR, Di Pietro V, Gendoo DMA, Belli A, Palin W, Davies DJ, Ahmed Z. Evaluation of transcriptomic changes after photobiomodulation in spinal cord injury. Sci Rep. 2025 Jan 25;15(1):3193. doi: 10.1038/s41598-025-87300-4.
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