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.

中文翻译：

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苯并[a]芘亚慢性给药通过抑制大鼠 CaMK II/PKC/PKA-ERK-CREB ​​信号传导破坏海马长时程增强

苯并[a]芘 (B[a]P) 被认为是哺乳动物的神经毒性污染物，可能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)，一种神经细胞中的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研究阐明，特别是 B[a]P 对 NMDAR 下游信号转导通路的影响。在本研究中，我们检查了亚慢性给药 B[a]P 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着缺陷以及海马 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抑制 NMDAR NR1 亚基转录和蛋白质磷酸化有关。更重要的是，在 2.5 和 6.25 mg/kg B[a]P 处理组均检测到海马中 CaMK II/PKC/PKA-ERK-CREB ​​信号通路的失活，表明 NMDAR 和下游信号通路中的多个靶点参与 B[a]P 诱导的神经毒性。