Adenosine A2A receptor dysfunction in the mouse hippocampus following benzyl butyl phthalate exposure through integrated transcriptomic and molecular dynamics analyses

Benzyl butyl phthalate (BBP) is widely used as a plasticizer in numerous products. BBP has ability to cross the blood–brain barrier, and it accumulates in neurons. Therefore, identifying any vulnerable target pathway through which BBP operates is necessary for understanding their neurotoxicity. Here, we investigated whether BBP may disrupt adenosine A2A receptor (ADORA2A) signalling using an integrated transcriptomic and computational framework. Publicly available RNA-seq data revealed that ADORA2A expression was repressed in BBP exposed mice (3.7-fold downregulation; log2FC = −1.87, p = 5 × 10 −5 ), together with transcript isoform remodelling both annotated and novel isoforms, indicating possible effects on transcriptional regulation and transcript architecture. In addition, molecular docking was performed with ADORA2A-BBP, adenosine and preladenant as comparator ligands. BBP occupied the canonical ligand cavity, with a docking score of −7.46 kcal/mol. The findings suggest that BBP may interfere with hippocampal ADORA2A signalling, may pose a risk of neurotoxicity.