BMSCs transplantation downregulated NF-κB signaling pathways by being induced to differentiate into neurons in Experimental autoimmune encephalomyelitis (EAE) animal model

2020 ◽  
Author(s):  
Guo-yi Liu ◽  
Fan-yi Kong ◽  
Shu Ma ◽  
Li-yan Fu ◽  
Jia Geng
Keyword(s):  
Animal Model ◽  
Survival Rate ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Neurological Function ◽  
Autoimmune Encephalomyelitis ◽  
Neuroinflammatory Disease ◽  
Marrow Mesenchymal Stem Cells ◽  
Effective Therapeutic Strategy ◽  
Immunofluorescence Labeling ◽  
Experimental Autoimmune

Abstract Background: Multiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity and poorly find an effective therapeutic strategy. Currently, experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS.Methods: In our study, we performed flow cytometry to identify BMSCs. To systematically evaluate whether BMSCs can be differentiate into neuron cells, astrocytes and oligodendrocyte, we analyzed the biomarkers by immunofluorescence labeling. We demonstrated the effect of bone marrow mesenchymal stem Cells (BMSCs) transplant on the EAE animal model, and determined the expression of MAP-2, GFAP, and MBP in the cortex and hippocampus of mice.Results: Our results showed that BMSCs could be induced to differentiate into neuron cells astrocytes and oligodendrocyte. BMSCs transplant improved the survival rate, neurological function scores, and obvious remyelination of mice in BMSCs transplantation group was significantly higher than EAE group (P<0.01). Morever, BMSCs transplant decreased the levels of IL-2, IL-10, IL-17 and IL-22 in the serum of EAE mice. Western blotting showed that the expression of NF-κB, IκB-α and IL-17 was decreased in BMSCs transplant group.Conclusions: Herein, our results revealed that BMSCs were transplanted into the brain of EAE mice, differentiated into neurons, improved the survival rate, neurological function recovery and the extent of demyelination in EAE mice by downregulation of NF-κB signaling pathway.

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

2021 ◽  
Author(s):  
William E. Barclay ◽  
M. Elizabeth Deerhake ◽  
Makoto Inoue ◽  
Toshiaki Nonaka ◽  
Kengo Nozaki ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Animal Model ◽  
Cell Death ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammasome Activation ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.SIGNIFICANCE STATEMENTInflammasome activation in the peripheral immune system is pathogenic in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, inflammasome activity in the central nervous system (CNS) is largely unexplored. Here, we used genetically modified mice to determine inflammasome activation in the CNS during EAE. Our data indicated heightened AIM2 inflammasome activation in astrocytes after the disease peak. Unexpectedly, neither CNS-infiltrated myeloid cells nor microglia were the primary cells with activated inflammasomes in SC during EAE. Despite AIM2 inflammasome activation, astrocytes did not undergo apparent cell death and produced little of the proinflammatory cytokine, IL-1β, during EAE. This study showed that CNS inflammasome activation occurs during EAE without associating with IL-1β-mediated inflammation.

scholarly journals Salate derivatives found in sunscreens block experimental autoimmune encephalomyelitis in mice

2017 ◽  
Vol 114 (32) ◽  
pp. 8528-8531 ◽  
Author(s):  
Yanping Wang ◽  
Steven J. Marling ◽  
Lori A. Plum ◽  
Hector F. DeLuca
Keyword(s):  
Animal Model ◽  
Autoimmune Disease ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Uv Radiation ◽  
Uv Light ◽  
Autoimmune Encephalomyelitis ◽  
Insight Into ◽  
Experimental Autoimmune

UV light suppresses experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, in mice and may be responsible for the decreased incidence of MS in equatorial regions. To test this concept further, we applied commercially available sunblock preparations to mice before exposing them to UV radiation. Surprisingly, some of the sunblock preparations blocked EAE without UV radiation. Furthermore, various sunblock preparations had variable ability to suppress EAE. By examining the components of the most effective agents, we identified homosalate and octisalate as the components responsible for suppressing EAE. Thus, salates may be useful in stopping the progression of MS, and may provide new insight into mechanisms of controlling autoimmune disease.

scholarly journals Environmental enrichment alleviates the deleterious effects of stress in experimental autoimmune encephalomyelitis

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732095980
Author(s):  
Antoine Philippe Fournier ◽  
Erwan Baudron ◽  
Isabelle Wagnon ◽  
Philippe Aubert ◽  
Denis Vivien ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Environmental Enrichment ◽  
Acute Stress ◽  
Stressful Events ◽  
Autoimmune Encephalomyelitis ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Experimental Autoimmune

Background Clinical observations support the hypothesis that stressful events increase relapse occurrence in multiple sclerosis patients, while stress-reduction strategies can modulate this effect. However, a direct cause-effect relationship between stress level and relapse cannot be firmly established from these data. Objectives The purpose of this work was to address whether modulation of stress could interfere with symptom relapse in an animal model of multiple sclerosis with relapsing-remitting course. Methods Mice bred in standard or enriched environment were subjected to repeated acute stress during the remission phase of relapsing-remitting PLP-induced experimental autoimmune encephalomyelitis. Results We report that repeated acute stress induced a twofold increase in relapse incidence in experimental autoimmune encephalomyelitis. On the other hand, environmental enrichment reduced relapse incidence and severity, and reversed the effects of repeated acute stress. Conclusion These data provide the platform for further studies on the biological processes that link stress and multiple sclerosis relapses in a suitable animal model.

scholarly journals Experimental autoimmune encephalomyelitis in the common marmoset: a translationally relevant model for the cause and course of multiple sclerosis

2019 ◽  
Vol 6 (1) ◽  
pp. 17-58 ◽  
Author(s):  
Bert A. &amp;apos;t Hart
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Common Marmoset ◽  
Preclinical Research ◽  
Autoimmune Encephalomyelitis ◽  
Neuroinflammatory Disease ◽  
Mouse Experimental Autoimmune Encephalomyelitis ◽  
Eae Model ◽  
Experimental Treatments ◽  
Experimental Autoimmune

Abstract. Aging Western societies are facing an increasing prevalence of chronic autoimmune-mediated inflammatory disorders (AIMIDs) for which treatments that are safe and effective are scarce. One of the main reasons for this situation is the lack of animal models, which accurately replicate clinical and pathological aspects of the human diseases. One important AIMID is the neuroinflammatory disease multiple sclerosis (MS), for which the mouse experimental autoimmune encephalomyelitis (EAE) model has been frequently used in preclinical research. Despite some successes, there is a long list of experimental treatments that have failed to reproduce promising effects observed in murine EAE models when they were tested in the clinic. This frustrating situation indicates a wide validity gap between mouse EAE and MS. This monography describes the development of an EAE model in nonhuman primates, which may help to bridge the gap.

scholarly journals BMSCs differentiated into neurons, astrocytes and oligodendrocytes alleviated the inflammation and demyelination of EAE mice models

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0243014
Author(s):  
Guo-yi Liu ◽  
Yan Wu ◽  
Fan-yi Kong ◽  
Shu Ma ◽  
Li-yan Fu ◽  
...  
Keyword(s):  
Disease Incidence ◽  
Inflammatory Factors ◽  
Autoimmune Encephalomyelitis ◽  
Inflammatory Infiltration ◽  
Neuroinflammatory Disease ◽  
Tnf Α ◽  
Marrow Mesenchymal Stem Cells ◽  
Effective Therapeutic Strategy

Multiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity. Currently, effective therapeutic strategy was poorly found in MS. Experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS. Cumulative research have shown that bone marrow mesenchymal stem Cells (BMSCs) transplantation could treat EAE animal models, but the mechanism was divergent. Here, we systematically evaluated whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes to alleviate the symptoms of EAE mice. We used Immunofluorescence staining to detect MAP-2, GFAP, and MBP to evaluate whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes. The effect of BMSCs transplantation on inflammatory infiltration and demyelination in EAE mice were detected by Hematoxylin-Eosin (H&E) and Luxol Fast Blue (LFB) staining, respectively. Inflammatory factors expression was detected by ELISA and RT-qPCR, respectively. Our results showed that BMSCs could be induced to differentiate into neuron cells, astrocytes and oligodendrocyte in vivo and in vitro, and BMSCs transplanted in EAE mice were easier to differentiate than normal mice. Moreover, transplanted BMSCs reduced neurological function scores and disease incidence of EAE mice. BMSCs transplantation alleviated the inflammation and demyelination of EAE mice. Finally, we found that BMSCs transplantation down-regulated the levels of pro-inflammatory factors TNF-α, IL-1β and IFN-γ, and up-regulated the levels of anti-inflammatory factors IL-10 and TGF-β. In conclusion, this study found that BMSCs could alleviate the inflammatory response and demyelination in EAE mice, which may be achieved by the differentiation of BMSCs into neurons, astrocytes and oligodendrocytes in EAE mice.

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