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[背景]环境烟草烟雾(ETS)暴露与发育缺陷和疾病相关,已知包括影响小脑的功能。然而,直接的生物学效应及内在的神经化学机制仍不清楚。[目的]明确并评估在大鼠小脑发育的关键时期,ETS暴露所导致的潜在神经化学变化。[方法]将出生后第8天(PD8)到第PD23的大鼠,每天暴露于ETS(总悬浮颗粒浓度为300、100和0μg/m3),然后测定行为、神经蛋白质组和细胞水平的反应。[结果]产后ETS暴露诱导在新环境中的运动反应升高,等同于安非他明刺激诱发的效果。ETS暴露大鼠小脑的线粒体亚蛋白质组明显受到干扰。研究结果显示,呈剂量依赖性的需氧过程上调是通过修饰和增加HK1转运至线粒体,伴随ATP合成酶表达的相应提高。ETS暴露也诱导总Dnm1l线粒体分裂因素呈剂量依赖性增加;虽然发现更活跃的膜结合Dnm1l呈低剂量。Dnm1l激活与线粒体染色更强相关,特别是在分子层,它独立于应力诱导的Bcl-2家族的动态。此外,电子显微镜观察显示,Dnm1l介导的线粒体分裂与生物合成增加而非分裂相关。[结论]出生后小脑发育的关键时期对ETS暴露的影响易感,会导致行为改变。ETS的生物效应部分是因为在通常严格控制的情况下,Dnm1l介导的线粒体活跃应答。这些结果显示环境暴露影响神经系统发育和功能的一种新的机制。
[Background] Environmental tobacco smoke (ETS) exposure is associated with developmental defects and diseases and is known to include effects on the cerebellum. However, direct biological effects and intrinsic neurochemical mechanisms remain unclear. [Objective] To identify and assess the potential neurochemical changes caused by ETS exposure during the critical period of rat cerebellar development. [Methods] Rats on day 8 postnatally (PD8) to day PD23 were exposed daily to ETS (total suspended particle concentrations of 300, 100, and 0 μg / m3), and behavioral, neuroprotein, and cellular levels were measured . [Results] Postpartum ETS exposure induced an increased motor response in the new milieu, equivalent to the effect of amphetamine stimulation. Mitochondria sub-proteomes exposed to ETS in rat cerebellum were significantly disturbed. The results showed that up-regulation of the aerobic process in a dose-dependent manner was achieved by modifying and increasing the transport of HK1 to mitochondria, accompanied by a corresponding increase in ATP synthase expression. ETS exposure also induced a dose-dependent increase in total Dnmll mitochondrial fission factors; although a more active membrane-bound Dnmll was found to be in low doses. Dnm1l activation is more strongly associated with mitochondrial staining, especially in the molecular layer, which is independent of the stress-induced dynamics of the Bcl-2 family. In addition, electron microscopy revealed that Dnmll-mediated mitochondrial division is associated with increased biosynthesis but not division. [Conclusion] The critical period of postnatal cerebellum development is susceptible to ETS exposure and leads to behavioral changes. The biological effect of ETS is due in part to the Dnmll-mediated mitochondrial active response under generally controlled conditions. These results show that environmental exposure affects a new mechanism of nervous system development and function.