Gao Dongxu, Wu Meifang, Wang Chonggang, Wang Yuanchuan, Zuo Zhenghong
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China; State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian 361005, China.
Aquat Toxicol. 2015 Oct;167:200-8. doi: 10.1016/j.aquatox.2015.08.013. Epub 2015 Sep 2.
Previous epidemiological and animal studies report that exposure to environmental pollutant exposure links to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Benzo[a]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, has been increasingly released into the environment during recent decades. So far, the role of BaP on the development of neurodegenerative diseases remaind unclear. This study aimed to determine whether chronic exposure to low dose BaP would cause neurodegenerative disease-like syndromes in zebrafish (Danio rerio). We exposed zebrafish, from early embryogenesis to adults, to environmentally relevant concentrations of BaP for 230 days. Our results indicated that BaP decreased the brain weight to body weight ratio, locomotor activity and cognitive ability; induced the loss of dopaminergic neurons; and resulted in neurodegeneration. In addition, obvious cell apoptosis in the brain was found. Furthermore, the neurotransmitter levels of dopamine and 3,4-dihydroxyphenylacetic acid, the mRNA levels of the genes encoding dopamine transporter, Parkinson protein 7, phosphatase and tensin-induced putative kinase 1, ubiquitin carboxy-terminal hydrolase L1, leucine-rich repeat serine/threonine kinase 2, amyloid precursor protein b, presenilin 1 and presenilin 2 were significantly down-regulated by BaP exposure. These findings suggest that chronic exposure to low dose BaP could cause the behavioral, neuropathological, neurochemical, and genetic features of neurodegenerative diseases. This study provides clues that BaP may constitute an important environmental risk factor for neurodegenerative diseases in humans.
以往的流行病学和动物研究报告称,接触环境污染物与帕金森病和阿尔茨海默病等神经退行性疾病有关。苯并[a]芘(BaP)是一种具有神经毒性的多环芳烃,近几十年来其在环境中的释放量不断增加。到目前为止,BaP在神经退行性疾病发展过程中的作用仍不清楚。本研究旨在确定长期低剂量接触BaP是否会在斑马鱼(Danio rerio)中引发类似神经退行性疾病的综合征。我们将斑马鱼从胚胎早期发育到成年期暴露于环境相关浓度的BaP中230天。我们的结果表明,BaP降低了脑重与体重的比值、运动活性和认知能力;诱导了多巴胺能神经元的损失;并导致了神经退行性变。此外,还发现大脑中存在明显的细胞凋亡。此外,BaP暴露显著下调了多巴胺和3,4-二羟基苯乙酸的神经递质水平以及编码多巴胺转运体、帕金森蛋白7、磷酸酶和张力蛋白诱导的假定激酶1、泛素羧基末端水解酶L1、富含亮氨酸重复序列的丝氨酸/苏氨酸激酶2、淀粉样前体蛋白b、早老素1和早老素2的基因的mRNA水平。这些发现表明,长期低剂量接触BaP可能导致神经退行性疾病的行为、神经病理学、神经化学和遗传特征。本研究提供了线索,表明BaP可能是人类神经退行性疾病的一个重要环境危险因素。