Shared Transcriptomic and Epigenomic Signatures Between Traumatic Brain Injury and Music Exposure: An Integrative...

Music-based interventions have shown promise in aiding recovery in individuals with brain damage (BD), including acquired and traumatic brain injury (ABI and TBI). To investigate the underlying molecular mechanisms, we conducted a study integrating transcriptomic and epigenomic data. We compared gene expression changes driven by musical stimuli in healthy individuals exposed to music with transcriptomic data from TBI patients, identifying 154 common differentially expressed genes (DEGs) affected in TBI and impacted by music, including STK35, HNRNPA0. These genes are notably involved in synaptic plasticity, and neurodegenerative processes. Epigenomic analysis revealed that 92 of these DEGs also exhibited significant differential methylation in TBI samples, particularly in genes associated with neurodevelopment, neuroinflammation, and mood regulation. Pathway enrichment and cross-validation in independent datasets of TBI patients highlighted the cGMP-PKG signaling pathway, a key regulator of memory and plasticity. Co-expression network analysis further revealed six gene modules significantly associated with TBI, including modules centered on TXNIP and ALG13 genes, previously implicated in neuroinflammation and epilepsy, two conditions commonly associated with TBI. Interestingly, several hub genes from these modules also showed sensitivity to musical stimuli, suggesting that music may target biologically relevant networks involved in TBI pathology. These findings reveal intriguing molecular parallels between signatures associated with TBI and the biological response to music exposure, providing a proof-of-concept for future investigation. This molecular insight suggests a potential role for music as a biologically grounded component of neurorehabilitation. However, future studies should directly assess transcriptomic and epigenomic responses to music-based interventions in BD patients.