Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis
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). S...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722003226 |
| _version_ | 1797954107739209728 |
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| author | Shylesh Bhaskaran Gaurav Kumar Nidheesh Thadathil Katarzyna M. Piekarz Sabira Mohammed Sergio Dominguez Lopez Rizwan Qaisar Dorothy Walton Jacob L. Brown Ashley Murphy Nataliya Smith Debra Saunders Michael J. Beckstead Scott Plafker Tommy L. Lewis, Jr. Rheal Towner Sathyaseelan S. Deepa Arlan Richardson Robert C. Axtell Holly Van Remmen |
| author_facet | Shylesh Bhaskaran Gaurav Kumar Nidheesh Thadathil Katarzyna M. Piekarz Sabira Mohammed Sergio Dominguez Lopez Rizwan Qaisar Dorothy Walton Jacob L. Brown Ashley Murphy Nataliya Smith Debra Saunders Michael J. Beckstead Scott Plafker Tommy L. Lewis, Jr. Rheal Towner Sathyaseelan S. Deepa Arlan Richardson Robert C. Axtell Holly Van Remmen |
| author_sort | Shylesh Bhaskaran |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T23:13:28Z |
| format | Article |
| id | doaj.art-81eb975c107342e8860817ab0704bc01 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-10T23:13:28Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-81eb975c107342e8860817ab0704bc012023-01-13T04:16:12ZengElsevierRedox Biology2213-23172023-02-0159102550Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosisShylesh Bhaskaran0Gaurav Kumar1Nidheesh Thadathil2Katarzyna M. Piekarz3Sabira Mohammed4Sergio Dominguez Lopez5Rizwan Qaisar6Dorothy Walton7Jacob L. Brown8Ashley Murphy9Nataliya Smith10Debra Saunders11Michael J. Beckstead12Scott Plafker13Tommy L. Lewis, Jr.14Rheal Towner15Sathyaseelan S. Deepa16Arlan Richardson17Robert C. Axtell18Holly Van Remmen19Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USAArthritis & Clinical Immunology, Oklahoma Medical Research Foundation, OK, USADepartment of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, OK, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USAStephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USA; Oklahoma City VA Medical Center, Oklahoma City, OK, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USAAdvanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, OK, USAAdvanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, OK, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USA; Oklahoma City VA Medical Center, Oklahoma City, OK, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USAAging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USAAdvanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, OK, USADepartment of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, OK, USA; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USADepartment of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, OK, USA; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma City VA Medical Center, Oklahoma City, OK, USAArthritis & Clinical Immunology, Oklahoma Medical Research Foundation, OK, USA; Corresponding author. Arthritis & Clinical Immunology,Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA.Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, OK, USA; Oklahoma City VA Medical Center, Oklahoma City, OK, USA; Corresponding author. Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA.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.http://www.sciencedirect.com/science/article/pii/S2213231722003226Mn superoxide dismutaseNeuronsDemyelinationMitochondriaMultiple sclerosisNecroptosis |
| spellingShingle | Shylesh Bhaskaran Gaurav Kumar Nidheesh Thadathil Katarzyna M. Piekarz Sabira Mohammed Sergio Dominguez Lopez Rizwan Qaisar Dorothy Walton Jacob L. Brown Ashley Murphy Nataliya Smith Debra Saunders Michael J. Beckstead Scott Plafker Tommy L. Lewis, Jr. Rheal Towner Sathyaseelan S. Deepa Arlan Richardson Robert C. Axtell Holly Van Remmen Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis Redox Biology Mn superoxide dismutase Neurons Demyelination Mitochondria Multiple sclerosis Necroptosis |
| title | Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis |
| title_full | Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis |
| title_fullStr | Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis |
| title_full_unstemmed | Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis |
| title_short | Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis |
| title_sort | neuronal deletion of mnsod in mice leads to demyelination inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis |
| topic | Mn superoxide dismutase Neurons Demyelination Mitochondria Multiple sclerosis Necroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722003226 |
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