| Summary: | Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon formed by the incomplete combustion of organic matter. Environmental B[a]P contamination poses a serious health risk to many organisms because the pollutant may negatively affect many physiological systems. As such, chronic exposure to B[a]P is known to lead to locomotor dysfunction and neurodegeneration in several organisms. In this study, we used the zebrafish model to delineate the acute toxic effects of B[a]P on the developing nervous system. We found that embryonic exposure of B[a]P downregulates <i>shh</i> and <i>isl1</i>, causing morphological hypoplasia in the telencephalon, ventral thalamus, hypothalamus, epiphysis and posterior commissure. Moreover, hypoxia-inducible factors (<i>hif1a</i> and <i>hif2a</i>) are repressed upon embryonic exposure of B[a]P, leading to reduced expression of the Hif-target genes, <i>epo</i> and <i>survivin</i>, which are associated with neural differentiation and maintenance. During normal embryogenesis, low-level oxidative stress regulates neuronal development and function. However, our experiments revealed that embryonic oxidative stress is greatly increased in B[a]<i>P-</i>treated embryos. The expression of <i>catalase</i> was decreased and <i>sod1</i> expression increased in B[a]<i>P-</i>treated embryos. These transcriptional changes were coincident with increased embryonic levels of H<sub>2</sub>O<sub>2</sub> and malondialdehyde, with the levels in B[a]<i>P-</i>treated fish similar to those in embryos treated with 120-μM H<sub>2</sub>O<sub>2</sub>. Together, our data suggest that reduced Hif signaling and increased oxidative stress are involved in B[a]<i>P-</i>induced acute neurotoxicity during embryogenesis.
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