Prenatal benzo[a]pyrene exposure impairs hippocampal synaptic plasticity and cognitive function in SD rat offspring during adolescence and adulthood via HDAC2-mediated histone deacetylation

Benzo[a]pyrene (B[a]P) is a widespread carcinogenic pollutant in the environment. Although previous studies have demonstrated the neurodevelopmental toxicity of B[a]P, the precise mechanisms underlying the neurotoxic effects induced by prenatal B[a]P exposure remain largely unknown. In the present study, pregnant Sprague-Dawley (SD) rats were injected intraperitoneally with 0, 10, 20, or 40 mg/kg-bw of B[a]P for three consecutive days on embryonic days 17–19. The learning and memory abilities of offspring were determined by Morris Water Maze (MWM) test, while the number of dendritic branches and the density of dendritic spines in hippocampal CA1 and DG regions were evaluated by Golgi-Cox staining at PND 45 and PND 75. The mRNA expression of BDNF, PSD-95, and SYP in offspring hippocampus were detected by qRT-PCR, and the protein expression of BDNF, PSD-95, SYP, HDAC2, acH3K9, and acH3K14 were measured by Western blotting or immunohistochemistry. CHIP-PCR was performed to further detect the levels of acH3K9 and acH3K14 in the promoter regions of BDNF and PSD-95 genes. Our results showed that rats prenatally exposed to B[a]P exhibited impaired spatial learning and memory abilities and the number of dendritic branches and the density of dendritic spines in the hippocampal CA1 and DG regions were significantly reduced during adolescence and adulthood. The expression of HDAC2 protein was significantly upregulated, while acH3K9, acH3K14, BDNF, PSD-95, and SYP protein levels were significantly downregulated in the hippocampus of B[a]P- exposed rats. In addition, CHIP results showed that prenatal B[a]P exposure markedly decreased the level of acH3K9 and acH3K14 in the promoter region of BDNF and PSD-95 gene in the hippocampus of PND 45 and PND 75 offspring. All of the results suggest that prenatal B[a]P exposure impairs cognitive function and hippocampal synaptic plasticity of offspring in adolescence and adulthood, and HDAC2-mediated histone deacetylation plays a crucial role in these deficits.