Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis.
Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis.
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DOI：
10.1016/j.redox.2022.102550
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发表时间：
2023-02
期刊：
影响因子：
11.4
通讯作者：
Van Remmen, Holly
中科院分区：
文献类型：
--
作者：
Bhaskaran, Shylesh;Kumar, Gaurav;Thadathil, Nidheesh;Piekarz, Katarzyna M.;Mohammed, Sabira;Lopez, Sergio Dominguez;Qaisar, Rizwan;Walton, Dorothy;Brown, Jacob L.;Murphy, Ashley;Smith, Nataliya;Saunders, Debra;Beckstead, Michael J.;Plafker, Scott;Lewis, Tommy L., Jr.;Towner, Rheal;Deepa, Sathyaseelan S.;Richardson, Arlan;Axtellb, Robert C.;Van Remmen, Holly
关键词：
神经元氧化应激与衰老和神经退行性疾病有关。在这里，我们研究了在Sod2组小鼠(I-Mn-Sod2KO)中使用神经元特异性Cre重组酶(I-Mn-Sod2KO)缺失锰超氧化物歧化酶(MnSOD)而导致的小鼠脊髓氧化应激增加的影响。脊髓神经元中SOD2的缺失与线粒体改变和过氧化氢的产生有关。表现为，I-Mn-Sod2 KO小鼠出现后肢瘫痪和抱抱行为，伴随着广泛的脱髓鞘和神经传导速度减慢，轴突变性，血脑屏障通透性增强，炎性细胞因子升高，小胶质细胞激活，中性粒细胞浸润和脊髓内坏死性下垂。相比之下，脊髓运动神经元数量、神经肌肉接头的神经支配、肌肉质量和收缩功能没有改变。总体而言，我们的发现表明，脊髓中MnSOD的丢失促进了脱髓鞘、炎症和进行性瘫痪的表型，类似于进行性多发性硬化症的表型。神经元特异性缺失Sod2及相关表型。
Neuronal oxidative stress has been implicated in aging and neurodegenerative disease. Here we investigated the impact of elevated oxidative stress induced in mouse spinal cord by deletion of Mn-Superoxide dismutase (MnSOD) using a neuron specific Cre recombinase in Sod2 floxed mice (i-mn-Sod2 KO). Sod2 deletion in spinal cord neurons was associated with mitochondrial alterations and peroxide generation. Phenotypically, i-mn-Sod2 KO mice experienced hindlimb paralysis and clasping behavior associated with extensive demyelination and reduced nerve conduction velocity, axonal degeneration, enhanced blood brain barrier permeability, elevated inflammatory cytokines, microglia activation, infiltration of neutrophils and necroptosis in spinal cord. In contrast, spinal cord motor neuron number, innervation of neuromuscular junctions, muscle mass, and contractile function were not altered. Overall, our findings show that loss of MnSOD in spinal cord promotes a phenotype of demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis. Neuron specific deletion of Sod2 and associated phenotypes.
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影响因子：
7.8
作者：
Bhaskaran S;Pollock N;C Macpherson P;Ahn B;Piekarz KM;Staunton CA;Brown JL;Qaisar R;Vasilaki A;Richardson A;McArdle A;Jackson MJ;Brooks SV;Van Remmen H
通讯作者：
Van Remmen H
影响因子：
4.8
作者：
Hill LK;Hoang DM;Chiriboga LA;Wisniewski T;Sadowski MJ;Wadghiri YZ
通讯作者：
Wadghiri YZ
影响因子：
2.9
作者：
Blesa J;Trigo-Damas I;Quiroga-Varela A;Jackson-Lewis VR
通讯作者：
Jackson-Lewis VR
影响因子：
7.7
作者：
Bhaskaran, Shylesh;Pharaoh, Gavin;Deepa, Sathyaseelan S.
通讯作者：
Deepa, Sathyaseelan S.
影响因子：
3.3
作者：
Bennett, Jami;Basivireddy, Jayasree;McQuaid, Stephen
通讯作者：
McQuaid, Stephen