Abstract：
Persistent organic pollutants (POPs), which encompass pesticides and industrial chemicals widely utilized across the globe, pose a covert threat to human health. β-hexachlorocyclohexane (β-HCH) is an organochlorine pesticide with striking stability, still illegally dumped in many countries, and recognized as responsible for several pathogenetic mechanisms. This study represents a pioneering exploration into the neurotoxic effects induced by the exposure to β-HCH specifically targeting neuronal cells (N2a), microglia (BV-2), and C57BL/6 mice. As shown by western blot and qPCR analyses, the administration of β-HCH triggered a modulation of NF-κB, a key factor influencing both inflammation and pro-inflammatory cytokines expression. We demonstrated by proteomic and western blot techniques epigenetic modifications in H3 histone induced by β-HCH. Histone acetylation of H3K9 and H3K27 increased in N2a, and in the prefrontal cortex of C57BL/6 mice administered with β-HCH, whereas it decreased in BV-2 cells and in the hippocampus. We also observed a severe detrimental effect on recognition memory and spatial navigation by the Novel Object Recognition Test (NORT) and the Object Place Recognition Task (OPRT) behavioural tests. Cognitive impairment was linked to decreased expression of the genes BDNF and SNAP-25, which are mediators involved in synaptic function and activity. The obtained results expand our understanding of the harmful impact produced by β-HCH exposure by highlighting its implication in the pathogenesis of neurological diseases. These findings will support intervention programs to limit the risk induced by exposure to POPs. Regulatory agencies should block further illicit use, causing environmental hazards and endangering human and animal health.
摘要：
持久性有机污染物(POPs)其中包括全球广泛使用的农药和工业化学品，对人类健康构成秘密威胁。β-六氯环己烷（β-HCH）是一种有机氯农药，具有惊人的稳定性，仍然在许多国家非法倾销，并被认为是几种致病机制的原因。这项研究代表了对暴露于β-HCH引起的神经毒性效应的开创性探索，特别是针对神经元细胞（N2a），小胶质细胞（BV-2），和C57BL/6小鼠。如westernblot和qPCR分析所示，β-HCH的给药触发了NF-κB的调节，影响炎症和促炎细胞因子表达的关键因素。我们通过蛋白质组学和蛋白质印迹技术证明了β-HCH诱导的H3组蛋白的表观遗传修饰。H3K9和H3K27的组蛋白乙酰化在N2a中增加，在给予β-HCH的C57BL/6小鼠的前额叶皮层中，而在BV-2细胞和海马中下降。我们还通过新型物体识别测试（NORT）和物体位置识别任务（OPRT）行为测试观察到对识别记忆和空间导航的严重不利影响。认知障碍与BDNF和SNAP-25基因的表达降低有关，它们是参与突触功能和活动的介质。所获得的结果通过强调β-HCH暴露在神经系统疾病发病机理中的意义，扩大了我们对β-HCH暴露所产生的有害影响的理解。这些发现将支持干预计划，以限制暴露于POPs引起的风险。监管机构应阻止进一步的非法使用，造成环境危害，危害人类和动物健康。
