The validity of animal models to explore the pathogenic role of the complement system in multiple sclerosis: A review
Animal models of multiple sclerosis (MS) have been extensively used to characterize the disease mechanisms in MS, as well as to identify potential pharmacologic targets for this condition. In recent years, the immune complement system has gained increased attention as an important effector in the pa...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1017484/full |
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| author | Nil Saez-Calveras Nil Saez-Calveras Amy L. Brewster Olaf Stuve Olaf Stuve Olaf Stuve |
| author_facet | Nil Saez-Calveras Nil Saez-Calveras Amy L. Brewster Olaf Stuve Olaf Stuve Olaf Stuve |
| author_sort | Nil Saez-Calveras |
| collection | DOAJ |
| description | Animal models of multiple sclerosis (MS) have been extensively used to characterize the disease mechanisms in MS, as well as to identify potential pharmacologic targets for this condition. In recent years, the immune complement system has gained increased attention as an important effector in the pathogenesis of MS. Evidence from histological, serum, and CSF studies of patients supports an involvement of complement in both relapsing-remitting and progressive MS. In this review, we discuss the history and advances made on the use of MS animal models to profile the effects of the complement system in this condition. The first studies that explored the complement system in the context of MS used cobra venom factor (CVF) as a complement depleting agent in experimental autoimmune encephalomyelitis (EAE) Lewis rats. Since then, multiple mice and rat models of MS have revealed a role of C3 and the alternative complement cascade in the opsonization and phagocytosis of myelin by microglia and myeloid cells. Studies using viral vectors, genetic knockouts and pharmacologic complement inhibitors have also shown an effect of complement in synaptic loss. Antibody-mediated EAE models have revealed an involvement of the C1 complex and the classical complement as an effector of the humoral response in this disease. C1q itself may also be involved in modulating microglia activation and oligodendrocyte differentiation in these animals. In addition, animal and in vitro models have revealed that multiple complement factors may act as modulators of both the innate and adaptive immune responses. Finally, evidence gathered from mice models suggests that the membrane attack complex (MAC) may even exert protective roles in the chronic stages of EAE. Overall, this review summarizes the importance of MS animal models to better characterize the role of the complement system and guide future therapeutic approaches in this condition. |
| first_indexed | 2024-04-11T16:58:25Z |
| format | Article |
| id | doaj.art-cdd63d542f3e4d958916ac59faacb98f |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-11T16:58:25Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-cdd63d542f3e4d958916ac59faacb98f2022-12-22T04:13:13ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-10-011510.3389/fnmol.2022.10174841017484The validity of animal models to explore the pathogenic role of the complement system in multiple sclerosis: A reviewNil Saez-Calveras0Nil Saez-Calveras1Amy L. Brewster2Olaf Stuve3Olaf Stuve4Olaf Stuve5Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesNeurology Section, Parkland Hospital, Dallas, TX, United StatesDepartment of Biological Sciences, Southern Methodist University, Dallas, TX, United StatesDepartment of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesNeurology Section, VA North Texas Health Care System, Dallas, TX, United StatesPeter O’Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, United StatesAnimal models of multiple sclerosis (MS) have been extensively used to characterize the disease mechanisms in MS, as well as to identify potential pharmacologic targets for this condition. In recent years, the immune complement system has gained increased attention as an important effector in the pathogenesis of MS. Evidence from histological, serum, and CSF studies of patients supports an involvement of complement in both relapsing-remitting and progressive MS. In this review, we discuss the history and advances made on the use of MS animal models to profile the effects of the complement system in this condition. The first studies that explored the complement system in the context of MS used cobra venom factor (CVF) as a complement depleting agent in experimental autoimmune encephalomyelitis (EAE) Lewis rats. Since then, multiple mice and rat models of MS have revealed a role of C3 and the alternative complement cascade in the opsonization and phagocytosis of myelin by microglia and myeloid cells. Studies using viral vectors, genetic knockouts and pharmacologic complement inhibitors have also shown an effect of complement in synaptic loss. Antibody-mediated EAE models have revealed an involvement of the C1 complex and the classical complement as an effector of the humoral response in this disease. C1q itself may also be involved in modulating microglia activation and oligodendrocyte differentiation in these animals. In addition, animal and in vitro models have revealed that multiple complement factors may act as modulators of both the innate and adaptive immune responses. Finally, evidence gathered from mice models suggests that the membrane attack complex (MAC) may even exert protective roles in the chronic stages of EAE. Overall, this review summarizes the importance of MS animal models to better characterize the role of the complement system and guide future therapeutic approaches in this condition.https://www.frontiersin.org/articles/10.3389/fnmol.2022.1017484/fullcomplement systemmultiple sclerosisexperimental autoimmune encephalomyelitisprogressive multiple sclerosissynaptic pruningadaptive immune response |
| spellingShingle | Nil Saez-Calveras Nil Saez-Calveras Amy L. Brewster Olaf Stuve Olaf Stuve Olaf Stuve The validity of animal models to explore the pathogenic role of the complement system in multiple sclerosis: A review Frontiers in Molecular Neuroscience complement system multiple sclerosis experimental autoimmune encephalomyelitis progressive multiple sclerosis synaptic pruning adaptive immune response |
| title | The validity of animal models to explore the pathogenic role of the complement system in multiple sclerosis: A review |
| title_full | The validity of animal models to explore the pathogenic role of the complement system in multiple sclerosis: A review |
| title_fullStr | The validity of animal models to explore the pathogenic role of the complement system in multiple sclerosis: A review |
| title_full_unstemmed | The validity of animal models to explore the pathogenic role of the complement system in multiple sclerosis: A review |
| title_short | The validity of animal models to explore the pathogenic role of the complement system in multiple sclerosis: A review |
| title_sort | validity of animal models to explore the pathogenic role of the complement system in multiple sclerosis a review |
| topic | complement system multiple sclerosis experimental autoimmune encephalomyelitis progressive multiple sclerosis synaptic pruning adaptive immune response |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1017484/full |
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