染砷小鼠脑突触结构变化及相关基因差异表达

Changes of synapse and differential expression of relevant genes in cerebrum of mice exposed to arsenic

目的观察染砷小鼠大脑神经突触结构变化及相关基因表达。方法30只昆明种小鼠,按体重分为3组,即对照组、1和4 mg/L染砷组,染毒60 d。应用电镜和基因芯片技术观察砷对小鼠大脑神经突触结构及相关基因表达的影响。结果对照组小鼠大脑突触结构清晰,突触前膜、间隙和后膜特化带清晰,前突触中可见较多的突触小泡。染砷组小鼠大脑突触前膜、间隙及后膜轮廓清晰,突触前膜的突触小泡数量明显减少。基因芯片结果显示,染砷组小鼠大脑突触相关基因差异表达共有10条。上调基因为依赖于钙-钙调蛋白的蛋白激酶IV(Camk4)、速激肽1(Tac1)、多巴胺受体D1A(Drd1a)和多巴胺受体D2(Drd2);表达下调的基因共有6条,分别为complexin蛋白2(Cplx2)、钙通道α1A亚单位(Cacna1a)、谷氨酸受体互变异构NMDA2B(Grin2b)、亲代谢性谷氨酸受体7(Grm7)、肌萎缩性(脊髓)侧索硬化2(Als2)和亲代谢性谷氨酸受体2(Grm2)。结论亚慢性砷暴露对小鼠大脑突触结构及相关基因表达造成损伤性影响,提示大脑神经元突触可能是砷神经毒性作用靶部位。

Objective To examine the influence of subchronic arsenic （As） exposure on synapse ultrastructures and expressions of relevant genes in cerebrum of mice. Methods Thirty mice were divided into three groups including two experimental groups（ 1 mg/L or 4 mg/L As2O3 ） and one control. AS2O3 was given for consecutive 60 days, followed by decollation. Changes of synapse ultrastructure and differential expressions of the relevant genes were examined with electron microscope and GeneChip technique. Results In controls, synaptic vesicle increased obviously within presynapse in cerebrum of the mice. Compared to the controls, synaptic vesicle decreased obviously within presynapse in cerebrum of the mice exposed to As. In genechip screening, 10 differential expressions of the relevant genes were observed in experimental groups. Among these genes, Camk4, Tacl, Drdl a and Drd2 were upregulated and Cplx2, Cacnal a, Grirl2b, Grm7, Als2 and Grin2 were downregulated. Conclusion Subchronic exposure to As may affect adversely synapse ultrastructure and expressions of relevant genes in cerebrum of mice. These results indicate that synapse in cerebrum may be a target of As- induced neurotoxicity.