Department of Health Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, China.
Department of Biochemistry and Molecular Biology, School of Preclinical Medicine, Shanxi Medical University, Taiyuan, China.
Environ Toxicol. 2020 Sep;35(9):961-970. doi: 10.1002/tox.22932. Epub 2020 Apr 7.
Benzo[a]pyrene (B[a]P) is recognized as a neurotoxic pollutant to mammals, which could impair learning and memory function. Although there is some evidence to suggest that N-methyl-d-aspartate receptor (NMDAR), a glutamate receptor and ion channel protein in nerve cells, is involved into the B[a]P induced neurotoxicity, the exact molecular mechanisms remain to be elucidated, particularly the effects of B[a]P on the NMDAR downstream signaling transduction pathways. In the present study, we examined the neurotoxicity of sub-chronic administrated B[a]P on male Sprague-Dawley rats. Our data suggested that B[a]P exposure caused significant deficits in learning and memory function and the impairment of hippocampal LTP in rats. Further mechanistic studies indicate that B[a]P-induced learning and memory deficits are associated with the inhibition of NMDAR NR1 subunit transcription and protein phosphorylation. More importantly, the inactivation of CaMK II/PKC/PKA-ERK-CREB signaling pathways in hippocampus was detected at both the 2.5 and 6.25 mg/kg B[a]P-treated groups, indicating that multiple targets in NMDAR and downstream signaling pathways are involved in the B[a]P-induced neurotoxicity.
苯并[a]芘（B[a]P）被认为是一种对哺乳动物具有神经毒性的污染物，可损害学习和记忆功能。尽管有一些证据表明，N-甲基-D-天冬氨酸受体（NMDAR）是神经细胞中的一种谷氨酸受体和离子通道蛋白，参与了 B[a]P 诱导的神经毒性，但确切的分子机制仍有待阐明，特别是 B[a]P 对 NMDAR 下游信号转导途径的影响。在本研究中，我们研究了亚慢性 B[a]P 处理对雄性 Sprague-Dawley 大鼠的神经毒性。我们的数据表明，B[a]P 暴露导致大鼠学习和记忆功能显著受损，海马长时程增强（LTP）受损。进一步的机制研究表明，B[a]P 诱导的学习和记忆缺陷与 NMDAR NR1 亚基转录和蛋白磷酸化的抑制有关。更重要的是，在 2.5 和 6.25mg/kg B[a]P 处理组的海马中检测到 CaMK II/PKC/PKA-ERK-CREB 信号通路失活，表明 NMDAR 和下游信号通路中的多个靶标参与了 B[a]P 诱导的神经毒性。
