Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie
Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie
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DOI：
10.1111/j.1365-2990.2010.01065.x
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发表时间：
2010-06-01
影响因子：
5
通讯作者：
Badiola, J. J.
中科院分区：
文献类型：
--
作者：
Bolea, R.;Hortells, P.;Badiola, J. J.
目的：缺乏 PrPc 和感染朊病毒的小鼠大脑中的铜和锰水平发生变化。本研究的目的是分析锰和铜失衡对痒病感染 Tga20 小鼠模型中神经元凋亡的影响。方法：在用以下几种饮食之一治疗的痒病感染小鼠和对照 Tga20 小鼠的脑部 9 个区域中，评估了凋亡蛋白 Bax 和活性 caspase-3 的免疫反应性：贫铜 (-Cu)、负载锰 (+Mn)、贫铜/负载锰 (-Cu+Mn) 和常规饮食。 NeuN 的免疫组织化学测定用于检测可能的神经元损失。结果：用改良饮食喂养的动物，特别是用贫铜饮食治疗的动物，细胞内 Bax 检测显着降低。活性 caspase-3 的减少主要在饲喂强化锰饮食的动物中观察到。我们的结果表明，-Cu、-Cu+Mn 和+Mn 饮食可防止感染瘙痒病的小鼠发生细胞凋亡。然而，NeuN 免疫标记定量显示，没有饮食足以阻止神经元死亡。结论：在细胞凋亡诱导方面，Tga20 小鼠对朊病毒感染的反应与报道的其他小鼠模型相似。我们的结果证明了 -Cu、-Cu+Mn 和 +Mn 饮食在瘙痒病小鼠模型中的神经保护作用。然而，朊病毒感染引起的神经元死亡似乎与细胞凋亡标记信号传导无关。此外，铜改良饮食对 Tga20 对照和感染小鼠中的朊病毒转基因可能产生的毒性具有神经保护作用，尽管补充锰不能抵消这种毒性。
Aims: Copper and manganese levels are altered in mice both lacking PrPc and prion-infected brains. The aim of this study was to analyse the effects of manganese and copper imbalance on neuronal apoptosis in a scrapie-infected Tga20 mouse model. Methods: Immunoreactivities for the apoptotic proteins Bax and active caspase-3 were evaluated in nine regions of the brain of scrapie-infected and control Tga20 mice treated with one of several diets: depleted cooper (-Cu), loaded manganese (+Mn), depleted copper/loaded manganese (-Cu+Mn) and regular diet. Immunohistochemical determination of NeuN was used to detect possible neuronal loss. Results: Intracellular Bax detection was significantly decreased in animals fed with modified diets, particularly in those treated with copper-depleted diets. A decrease in active caspase-3 was primarily observed in animals fed with enhanced manganese diets. Our results show that the -Cu, -Cu+Mn and +Mn diets protected against apoptosis in scrapie-infected mice. However, NeuN immunolabelling quantification revealed that no diet was sufficient to arrest neuronal death. Conclusions: With regard to apoptosis induction, the response of Tga20 mice to prion infection was similar to that reported for other mice models. Our results demonstrate the neuroprotective effects of -Cu, -Cu+Mn and +Mn diets in a murine model of scrapie. However, neuronal death induced by infection with prions seems to be independent of apoptosis marker signalling. Moreover, copper-modified diets were neuroprotective against the possible toxicity of the prion transgene in Tga20 control and infected mice even though manganese supplementation could not counteract this toxicity.