Long-term dysregulation of histone acetylation, BDNF expression, and the hippocampal transcriptome in adult rats exhibiting a depressive-like phenotype following repeated chlorpyrifos exposure

Repeated chlorpyrifos exposure in adult rats is linked to long-term reductions in hippocampal BDNF protein and Bdnf promoter IV H3K9 acetylation, alongside 100 differentially expressed genes.

• Why it matters: Occupational chlorpyrifos exposure in adults is associated with higher depression risk, but the persistent molecular changes underlying depressive-like states are unclear.
• What they did: Adult rats received chlorpyrifos at 5 mg/kg/day for 21 days; three months later, hippocampal HDAC3 and HDAC5 were upregulated, Bdnf promoter IV H3K9ac occupancy was measured by chromatin immunoprecipitation, and exploratory RNA-seq identified genes with FDR < 5%.
• The result: CPF rats showed reduced H3K9ac at Bdnf promoter IV with decreased BDNF protein, plus 100 significantly differentially expressed hippocampal genes enriched for neurogenesis, neuronal projections, and myelination pathways.

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