Animal Pathology Department, University of Zaragoza, Zaragoza, Spain.
Neuropathol Appl Neurobiol. 2010 Jun;36(4):300-11. doi: 10.1111/j.1365-2990.2010.01065.x. Epub 2010 Jan 7.
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.
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.
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.
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.
缺乏 PrPc 的小鼠和感染朊病毒的大脑中的铜和锰水平发生改变。本研究的目的是分析锰和铜失衡对感染瘙痒病的 Tga20 小鼠模型中神经元凋亡的影响。
用几种饮食（缺铜（-Cu）、高锰（+Mn）、缺铜/高锰（-Cu+Mn）和常规饮食）处理感染瘙痒病的 Tga20 小鼠和对照 Tga20 小鼠，分析脑内 9 个区域的凋亡蛋白 Bax 和活性半胱天冬酶-3 的免疫反应。用 NeuN 免疫组化检测可能的神经元丢失。
用改良饮食喂养的动物中细胞内 Bax 的检测明显减少，特别是用铜缺乏饮食喂养的动物。在给予高锰饮食的动物中，主要观察到活性半胱天冬酶-3 的减少。结果表明，-Cu、-Cu+Mn 和+Mn 饮食可防止感染瘙痒病的小鼠发生凋亡。然而，NeuN 免疫标记定量显示，没有一种饮食足以阻止神经元死亡。
就凋亡诱导而言，Tga20 小鼠对朊病毒感染的反应与其他小鼠模型报道的反应相似。本研究结果表明，-Cu、-Cu+Mn 和+Mn 饮食对瘙痒病的小鼠模型具有神经保护作用。然而，感染朊病毒引起的神经元死亡似乎与凋亡标志物信号无关。此外，即使锰补充不能抵消这种毒性，铜修饰饮食对 Tga20 对照和感染小鼠中的朊病毒转基因的潜在毒性也具有神经保护作用。
