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Bisphenol A (BPA), a component of plastic products, can penetrate the blood-brain barrier and pose a threat to the nervous system. Selenium (Se) deficiency can also cause nervous system damage. Resulting from the rapid industrial development, BPA pollution and Se deficiency often coexist. However, it is unclear whether brain damage in chickens caused by BPA exposure and Se deficiency is related to the crosstalk disorder between mitophagy and apoptosis. In this study, 60 chickens (1 day old) were fed with a diet that contained 20 mg/kg BPA but was insufficient in Se (only 0.039 mg/kg) for 42 days to establish a chicken brain injury model. In vitro, the primary chicken embryo brain neurons were treated for 24 h with Se-deficient medium containing 75 μM BPA. The results showed that BPA exposure and Se deficiency inhibited the expression of the mitochondrial respiratory chain complex in brain neurons, and a large number of mitochondrial reactive oxygen species were released. Furthermore, the expression levels of mitochondrial fusion proteins (OPA1, Mfn1, and Mfn2) decreased, while the expression levels of mitochondrial fission proteins (Drp1, Mff, and Fis1) increased, thus exacerbating mitochondrial division. In addition, the results of immunofluorescence and flow cytometry analysis, as well as the elevated expressions of mitophagy related genes (PINK1, Parkin, ATG5, and LC3II/I) and pro-apoptotic markers (Bax, Cytc, Caspase3, and Caspase9) indicated that BPA exposure and Se deficiency disrupted the crosstalk homeostasis between mitophagy and apoptosis. However, this crosstalk homeostasis was restored after Mito-Tempo and Rapamycin treatment. In contrast, 3-methyladenine treatment exacerbated this crosstalk disorder. In conclusion, BPA exposure and Se deficiency can induce mitochondrial reactive oxygen species bursts and disorders of mitochondrial dynamics by destroying the mitochondrial respiratory chain complex. The result is indicative of an imbalance in mitochondrial autophagy and apoptosis crosstalk homeostasis, which damages the chicken brain. Copyright © 2023. Published by Elsevier B.V.
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