Supplementary Materials<b> </b>for <b>Whole RNA sequencing of mouse cortex and hippocampus after 808 nm transcranial photobiomodulation: mechanisms of light therapy for Alzheimer’s disease</b>

Light therapy using 600–980 nm red and near-infrared (NIR) irradiation is currently actively utilized in clinics and extensively studied due to the positive outcomes it yields. However, the previously explored interactions between light and cells are associated with cellular pathways linked to the cytochrome-c-oxidase photoacceptor, reactive oxygen species and calcium ion receptors activated by light-induced depolarization of the cellular membrane. To identify new molecular mechanisms of tPBM on neuronal cells in vivo, we conducted the first-ever next-generation whole RNA sequencing (RNA-Seq) of the cortex and hippocampus of BALB/c mice following an 808 nm light treatment with a 30-day course of daily 1-hour sessions (36 J/cm² at 10 mW/cm²). RNA-Seq analysis of over 30,000 mRNA molecules for each studied brain region reveals significant dysregulation of transcription after tPBM. Transcriptional alterations were found in 1,005 genes in the hippocampus and 1,482 genes in the cortex. Pathway-gene enrichment network analyses identified 50 pathways involving these genes. The constructed disease-gene network highlights potential diseases in which gene expression may change after tPBM. Additionally, light also modulates the transcription of key genes identified as main risk factors for AD, involved in APP processing or associated with oxidative stress, inflammation and apoptosis, thereby supporting AD development.