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Synaptic dopamine release is positively regulated by SNAP-25 that involves in benzo[a]pyrene-induced neurotoxicity
- Yang, Kai, Jiang, Xuejun, Cheng, Shuqun, Bai, LuLu, Xia, Yinyin, Chen, Chengzhi, Meng, Pan, Wang, Jing, Li, Chunlin, Tang, Qianghu, Cao, Xianqing, Tu, Baijie
- Chemosphere 2019 v.237 pp. 124378
- CRISPR-Cas systems, apoptosis, benzo(a)pyrene, cerebral cortex, cytotoxicity, dopamine, dopamine receptors, intragastric administration, neurotoxicity, plasmids, pollutants, rats, synaptic transmission
- Benzo[a]pyrene (B[a]P) is a ubiquitous neurotoxic pollutant that widely distributes in the natural environment. However, the exact mechanism of B[a]P-induced neurotoxicity has not been well established. As one key synaptic protein, SNAP-25 plays an important role in the regulation of neurotransmitter release, including synaptic dopamine release. In this study, we demonstrated that, after intragastric administration of B[a]P in rats aged postnatal day 5 for 7 weeks, B[a]P significantly increased the level of dopamine and the expression of SNAP-25, dopamine receptor 1 (DRD1) and DRD 3. Moreover, treatment of B[a]P also caused the ultra-structural pathological changes in the cerebral cortex of rats. To further reveal the potential role of SNAP-25 in the regulation of DRDs, we treated the dopaminergic PC-12 cells with 20 μM B[a]P for 24 h. A significant cytotoxicity and apoptosis were observed, and more importantly, we found that SNAP-25, DRD 1 and DRD 3 co-localized in the cells, and down-regulation of SNAP-25 by CRISPR-Cas9 plasmid remarkably reduced the expression of DRD1 and DRD3. Together, our findings suggest that, synaptic dopamine release may be positively regulated by SNAP-25 via its receptors, and thus affecting the neurotoxicity induced by B[a]P.