氧化还原失衡被认为有助于与一些神经退行性疾病的发生发展。我们的目标是开发一个动物模型，在中枢神经系统表现出神经元特异性氧化应激研究的后果，最终找到线索对神经细胞稳态氧化损伤的病理机制。因此，产生了一种新的神经元特异性超氧化物歧化酶2(SOD2)-缺陷小鼠通过删除使用CaMKIIα启动子驱动Cre表达SOD2基因3外显子。这些神经元特异性基因敲除小鼠(sod2nko)，虽然出世在正常的频率，死在关键生长发育迟缓，4周龄，能源严重失败，和几个神经表型。
此外，sod2nko小鼠表现出严重的神经元的改变如星形胶质细胞，神经元细胞周期的抑制作用，并诱导细胞凋亡。JNK的激活，p53的稳定，因此活性氧的积累，是最有可能在sod2nko小鼠神经细胞凋亡的诱导。值得注意的是，下丘脑调节糖代谢的影响，从而引起的坏死性脑病变的小鼠sod2nko。总之，我们的研究结果表明，独家缺乏神经元中结果在受损的中枢调节能量平衡，导致持续性低血糖低血糖相关的神经病理学，SOD2，和突变小鼠的早期致死。-麦迪库马尔，G.，塔尔，罗斯福，鲍曼，B，scharffetter Kochanek博士，K，和沃斯，T.神经元氧化还原失衡的结果改变能量平衡和出生后早期的杀伤力。
原文
Neuronal redox imbalance results in altered energy homeostasis and early postnatal lethality
Abstract
Redox imbalance is believed to contribute to the development and progression of several neurodegenerative disorders. Our aim was to develop an animal model that exhibits neuron-specific oxidative stress in the CNS to study the consequences and eventually find clues regarding the pathomechanisms of oxidative insults in neuronal homeostasis. We therefore generated a novel neuron-specific superoxide dismutase 2 (SOD2)-deficient mouse by deleting exon 3 of the SOD2 gene using CamKIIα promoter-driven Cre expression. These neuron-specific SOD2 knockout (SOD2nko) mice, although born at normal frequencies, died at the age of 4 weeks with critical growth retardation, severe energy failure, and several neurologic phenotypes. In addition, SOD2nko mice exhibited severe neuronal alterations such as reactive astrogliosis, neuronal cell cycle inhibition, and induction of apoptosis. JNK activation and stabilization of p53, as a result of reactive oxygen species accumulation, are most likely the inducers of neuronal apoptosis in SOD2nko mice. It is remarkable that hypothalamic regulation of glucose metabolism was affected, which in turn induced necrotic brain lesions in SOD2nko mice. Taken together, our findings suggest that exclusive deficiency of SOD2 in neurons results in an impaired central regulation of energy homeostasis that leads to persistent hypoglycemia, hypoglycemia-related neuropathology, and an early lethality of the mutant mice.—Maity-Kumar, G., Thal, D. R., Baumann, B., Scharffetter-Kochanek, K., and Wirth, T. Neuronal redox imbalance results in altered energy homeostasis and early postnatal lethality.
