PCB 118 Exposure Modulates Chromatin Organization, Ribosome Biogenesis, and Autophagy-Related Pathways in...

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants associated with neurodevelopmental and neurodegenerative disorders. PCB 118 is one of the most abundant congeners and exerts neurotoxic effects, yet the molecular mechanisms underlying its impact on human neurons remain poorly understood. We investigated the molecular response of retinoic acid-differentiated, neuron-like SH-SY5Y cells exposed to 5 µM PCB 118 for 24 h, a concentration that did not affect cell viability. RNA sequencing identified 1239 differentially expressed genes. Functional enrichment and protein-protein interaction analyses identified upregulation of histone and chromatin structural genes, indicative of substantial chromatin remodeling. In parallel, a significant downregulation of genes involved in ribosome biogenesis and rRNA processing was observed, potentially indicating impairment of the protein synthesis machinery. These transcriptional changes point to a coordinated reprogramming of nuclear architecture and translational machinery, potentially compromising neuronal homeostasis. The modulation of proteostasis-related pathways further supports a mechanistic link between PCB 118 exposure and neuronal dysfunction. Our results provide a comprehensive transcriptional framework connecting PCB 118 to chromatin-mediated gene regulation and suppression of ribosome biogenesis in human neuron-like cells. This study offers mechanistic insights into how environmental PCB exposure may contribute to neurotoxicity and highlights molecular pathways potentially implicated in the development of neurodegenerative disorders.