scholarly journals Genetic deletion of Autotaxin from CD11b+ cells decreases the severity of experimental autoimmune encephalomyelitis

2019 ◽  
Author(s):  
Ioanna Ninou ◽  
Ioanna Sevastou ◽  
Christiana Magkrioti ◽  
Eleanna Kaffe ◽  
George Stamatakis ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Diseases ◽  
Activated Macrophages ◽  
Extracellular Production ◽  
Pathogenic Role ◽  
Autoimmune Encephalomyelitis ◽  
Genetic Deletion ◽  
Different Sources ◽  
Experimental Autoimmune

AbstractAutotaxin (ATX) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a growth factor-like signaling lysophospholipid. ATX and LPA signaling have been incriminated in the pathogenesis of different chronic inflammatory diseases and various types of cancer. In this report, deregulated ATX and LPA levels were detected in the spinal cord and plasma of mice during the development of experimental autoimmune encephalomyelitis (EAE). Among the different sources of ATX expression in the inflamed spinal cord, F4/80+CD11b+ cells, mostly activated macrophages and microglia, were found to express ATX, further suggesting an autocrine role for ATX/LPA in their activation, an EAE hallmark. Accordingly, ATX genetic deletion from CD11b+ cells attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in neuroinflammatory disorders.

scholarly journals Oral Administration of Probiotic Enterococcus Durans Ameliorates Experimental Autoimmune Encephalomyelitis in Mice

2021 ◽  
Author(s):  
Seyed Abdollah Samani ◽  
◽  
Mohamad Raman Moloudi ◽  
Rashid Ramezan Zadeh ◽  
Mohammad Abdi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Control Group ◽  
Immunomodulatory Activity ◽  
Spinal Cord Tissue ◽  
Autoimmune Encephalomyelitis ◽  
Enterococcus Durans ◽  
Experimental Autoimmune

Introduction: Probiotics, including lactobacilli, are known to induce immunomodulatory activity with promising effects in inflammatory diseases. In this study, the potential of Enterococcus durans and three various strains of lactobacilli (lacto-mix), Including L.rhamnosus, L.casei, and L.plantarum for prevention of Experimental Autoimmune Encephalomyelitis (EAE) features were evaluated. Methods: C57BL/6 female mice were inoculated with (MOG35-55) / (CFA) to induce EAE. Different groups (five groups: n = 6 in each group) of animals received saline or probiotics by oral gavage with 200 µl of lactobacilli (1.5 *108 CFU/ml) for 2 week before the immunization and during the test for one month. Results: Histopathological studies showed an increase in infiltration of inflammatory cells and destruction of the myelin membrane in the EAE group but a decrease in the probiotic-treated animals. Pro-inflammatory cytokines (IL-17 and IFN-g) concentration in the supernatant of the brain and spinal cord tissues showed a significant increase in the EAE compared with the normal saline group (p <0.01), while in the spinal cord tissue there was a decrease in IL-17 in those animals treated with the Lacto-mix and Edu + Lacto- mix (p <0.01) and a significant decrease in IFN-g in those animals that received Edu (p <0.05). Western blot analysis of MMP-9 and MBP proteins showed a decrease and increase in treatment and EAE groups, compared to the normal control group respectively. Conclusion: our data suggest that probiotic Enterococcus durans and lacto-mix had a preventive effect against EAE but further studies are needed to clarify the exact mechanisms and their application in preclinical and clinical trials.

scholarly journals Oral Administration of Probiotic Enterococcus Durans Ameliorates Experimental Autoimmune Encephalomyelitis in Mice

2021 ◽  
Author(s):  
Seyed Abdollah Samani ◽  
◽  
Mohamad Raman Moloudi ◽  
Rashid Ramezan Zadeh ◽  
Mohammad Abdi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Diseases ◽  
Control Group ◽  
Immunomodulatory Activity ◽  
Autoimmune Encephalomyelitis ◽  
Enterococcus Durans ◽  
Pathologic Features ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a myelin-degenerating autoimmune disease in the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE), due to its clinical and pathologic features similar to multiple sclerosis, is widely used in many studies of this disease as an effective and similar model. Probiotics, comprising lactobacilli, are known to induce immunomodulatory activity with hopeful effects in inflammatory diseases. In this study, the potential of Enterococcus durans and three various strains of lactobacilli (lacto-mix), Including L.rhamnosus, L.casei, and L.plantarum was tested for prevention of EAE features. C57BL/6 female mice were inoculated with (MOG35-55) / (CFA) to induce EAE. Different groups (five groups: n = 6 in each group) of animals received saline or probiotics. Histopathological studies showed an increase in infiltration of inflammatory cells and destruction of the myelin membrane in the EAE group but reduced in the probiotic-treated animals. The concentration of Pro-inflammatory cytokines (IL-17 and IFN-ɣ) in the supernatant of the brain and spinal cord homogenized tissues was significantly increased in EAE compared with the normal saline group. While in the spinal cord, the levels of IL-17 decreased in animals treated with Lacto-mix and Edu + Lacto- mix and a level of IFN-ɣ in animals receiving Edu decreased significantly. In addition, Western blot analysis of MMP-9 and MBP proteins decreased and increased in treatment and EAE groups compared to the normal control group respectively. Collectively, our data indicate that probiotic Enterococcus durans and lacto-mix have a preventive effect on EAE, but more studies are needed to diagnose precise mechanisms and their application in preclinical and clinical trials.

scholarly journals Axonal damage in spinal cord is associated with gray matter atrophy in sensorimotor cortex in experimental autoimmune encephalomyelitis

2019 ◽  
Vol 26 (3) ◽  
pp. 294-303 ◽  
Author(s):  
Cassandra E Meyer ◽  
Josephine L Gao ◽  
James Ying-Jie Cheng ◽  
Mandavi R Oberoi ◽  
Hadley Johnsonbaugh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gray Matter ◽  
Sensorimotor Cortex ◽  
Axonal Damage ◽  
Strongly Correlated ◽  
Autoimmune Encephalomyelitis ◽  
Normal Controls ◽  
Experimental Autoimmune

Background: Gray matter (GM) atrophy in brain is one of the best predictors of long-term disability in multiple sclerosis (MS), and recent findings have revealed that localized GM atrophy is associated with clinical disabilities. GM atrophy associated with each disability mapped to a distinct brain region, revealing a disability-specific atlas (DSA) of GM loss. Objective: To uncover the mechanisms underlying the development of localized GM atrophy. Methods: We used voxel-based morphometry (VBM) to evaluate localized GM atrophy and Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY) to evaluate specific pathologies in mice with experimental autoimmune encephalomyelitis (EAE). Results: We observed extensive GM atrophy throughout the cerebral cortex, with additional foci in the thalamus and caudoputamen, in mice with EAE compared to normal controls. Next, we generated pathology-specific atlases (PSAs), voxelwise mappings of the correlation between specific pathologies and localized GM atrophy. Interestingly, axonal damage (end-bulbs and ovoids) in the spinal cord strongly correlated with GM atrophy in the sensorimotor cortex of the brain. Conclusion: The combination of VBM with CLARITY in EAE can localize GM atrophy in brain that is associated with a specific pathology in spinal cord, revealing a PSA of GM loss.

scholarly journals Characterization of microglial transcriptomes in the brain and spinal cord of mice in early and late experimental autoimmune encephalomyelitis using a RiboTag strategy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaona Acharjee ◽  
Paul M. K. Gordon ◽  
Benjamin H. Lee ◽  
Justin Read ◽  
Matthew L. Workentine ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Expression Patterns ◽  
Immune Functions ◽  
Autoimmune Encephalomyelitis ◽  
Transcriptional Changes ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Experimental Autoimmune

AbstractMicroglia play an important role in the pathogenesis of multiple sclerosis and the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). To more fully understand the role of microglia in EAE we characterized microglial transcriptomes before the onset of motor symptoms (pre-onset) and during symptomatic EAE. We compared the transcriptome in brain, where behavioral changes are initiated, and spinal cord, where damage is revealed as motor and sensory deficits. We used a RiboTag strategy to characterize ribosome-bound mRNA only in microglia without incurring possible transcriptional changes after cell isolation. Brain and spinal cord samples clustered separately at both stages of EAE, indicating regional heterogeneity. Differences in gene expression were observed in the brain and spinal cord of pre-onset and symptomatic animals with most profound effects in the spinal cord of symptomatic animals. Canonical pathway analysis revealed changes in neuroinflammatory pathways, immune functions and enhanced cell division in both pre-onset and symptomatic brain and spinal cord. We also observed a continuum of many pathways at pre-onset stage that continue into the symptomatic stage of EAE. Our results provide additional evidence of regional and temporal heterogeneity in microglial gene expression patterns that may help in understanding mechanisms underlying various symptomology in MS.

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