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Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) is widely used as a broad-spectrum herbicide. Animal studies have demonstrated that ATR exposure can cause cell death in dopaminergic neurons. The molecular mechanisms underlying ATR-induced neuronal cell death, however, are unknown. In this study, we investigated the autophagy and apoptosis induced by ATR in dopaminergic neurons in vivo. Wistar rats were administered with ATR at doses of 10, 50 and 100 mg/kg body weight by oral gavage for three months. In terms of histopathology, the expression of autophagy- and apoptosis-related genes as well as proteins related to the Beclin-1/B-cell lymphoma 2 (Bcl-2) autophagy and apoptosis pathways were examined in the rat nigrostriatal dopaminergic system. We observed degenerative micromorphology indicative of neuronal apoptosis and mitochondrial autophagy by electron microscopy in ATR-exposed rat striatum. The rat ventral mesencephalon in the ATR-exposed groups also showed increased expression of Beclin-1, LC3-II, Bax and Caspase-9, and decreased expression of tyrosine hydroxylase (TH), Bcl-xl and Bcl-2. These findings indicate that ATR may induce autophagy- and apoptosis-related changes in doparminergic neurons. Furthermore, this induction may be regulated by the Beclin-1 and Bcl-2 autophagy and apoptosis pathways, and this may help to better understand the mechanism underlying the neurotoxicity of ATR.

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Bisphenol A (BPA) is one of the most widely produced chemicals in the world used in the production of epoxy resins and polycarbonate plastics. BPA is easily migrated from the outer packaging to the contents. Due to the lipophilic property, BPA is easily accumulated in organisms. Perinatal low-dose BPA exposure alters brain neural development in later generations. In this study, after BPA treatment, the spontaneous movement of zebrafish larvae from the cleavage period to the segmentation period (1–24 hpf) was significantly decreased, with speed decreasing by 18.97% and distance decreasing between 18.4 and 29.7% compared to controls. Transcriptomics analysis showed that 131 genes were significantly differentially expressed in the exposed group during the 1–24 hpf period, among which 39 genes were significantly upregulated and 92 genes were significantly downregulated. The GO enrichment analysis, gene function analysis and real-time quantitative PCR of differentially expressed genes showed that the mRNA level of guanine deaminase (cypin) decreased significantly in the 1–24 hpf period. Moreover, during the 1–24 hpf period, BPA exposure reduced guanine deaminase activity. Therefore, we confirmed that cypin is a key sensitive gene for BPA during this period. Finally, the cypin mRNA microinjection verified that the cypin level of zebrafish larvae was restored, leading to the restoration of the locomotor activity. Taken together, the current results show that the sensitive period of BPA to zebrafish embryos is from the cleavage period to the segmentation period (1–24 hpf), and cypin is a potential target for BPA-induced neurodevelopmental toxicity. This study provides a potential sensitive period and a potential target for the deep understanding of neurodevelopmental toxicity mechanisms caused by BPA.

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