scholarly journals Immunomodulation Eliminates Inflammation in the Hippocampus in Experimental Autoimmune Encephalomyelitis, but Does Not Ameliorate Anxiety-Like Behavior

2021 ◽  
Vol 12 ◽  
Author(s):  
Pece Kocovski ◽  
Nuzhat Tabassum-Sheikh ◽  
Stephanie Marinis ◽  
Phuc T. Dang ◽  
Matthew W. Hale ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Treatment Strategies ◽  
The Other ◽  
Autoimmune Encephalomyelitis ◽  
Inflammatory Infiltration ◽  
Other Hand ◽  
Wide Range ◽  
Sphingosine 1 Phosphate ◽  
Novel Treatment Strategies ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system, characterized by an unpredictable disease course and a wide range of symptoms. Emotional and cognitive deficits are now recognized as primary disease manifestations and not simply the consequence of living with a chronic condition, raising questions regarding the efficacy of current therapeutics for these specific symptoms. Mechanisms underlying psychiatric sequelae in MS are believed to be similar to those underlying pathogenesis, that is mediated by cytokines and other inflammatory mediators. To gain insight into the pathogenesis of MS depression, we performed behavioral assays in the murine experimental autoimmune encephalomyelitis (EAE) MS model, in the presence or absence of immunomodulation using the drug FTY720, an analogue of the lipid signaling molecule sphingosine-1-phosphate (S1P). Specifically, mice were challenged with the elevated plus maze (EPM) test, a validated experimental paradigm for rodent-specific anxiety-like behavior. FTY720 treatment failed to ameliorate anxiety-like symptoms, irrespective of dosage. On the other hand, it was effective in reducing inflammatory infiltration, microglial reactivity and levels of pro-inflammatory molecules in the hippocampus, confirming the anti-inflammatory capacity of treatment. To explore the absence of FTY720 effect on behavior, we confirmed expression of S1P receptors (S1PR) S1PR1, S1PR3 and S1PR5 in the hippocampus and mapped the dynamics of these receptors in response to drug treatment alone, or in combination with EAE induction. We identified a complex pattern of responses, differing between (1) receptors, (2) dosage and (3) hippocampal sub-field. FTY720 treatment in the absence of EAE resulted in overall downregulation of S1PR1 and S1PR3, while S1PR5 exhibited a dose-dependent upregulation. EAE induction alone resulted in overall downregulation of all three receptors. On the other hand, combined FTY720 and EAE showed generally no effect on S1PR1 and S1PR3 expression except for the fimbrium region, but strong upregulation of S1PR5 over the range of doses examined. These data illustrate a hitherto undescribed complexity of S1PR response to FTY720 in the hippocampus, independent of drug effect on effector immune cells, but simultaneously emphasize the need to explore novel treatment strategies to specifically address mood disorders in MS.

scholarly journals Partial Deficiency of Sphingosine-1-Phosphate Lyase Confers Protection in Experimental Autoimmune Encephalomyelitis

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e59630 ◽  
Author(s):  
Andreas Billich ◽  
Thomas Baumruker ◽  
Christian Beerli ◽  
Marc Bigaud ◽  
Christian Bruns ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Sphingosine 1 Phosphate ◽  
Partial Deficiency ◽  
Experimental Autoimmune

scholarly journals Sphingosine 1-Phosphate Receptor 1 (S1P1) Upregulation and Amelioration of Experimental Autoimmune Encephalomyelitis by an S1P1 Antagonist

2012 ◽  
Vol 83 (2) ◽  
pp. 316-321 ◽  
Author(s):  
Stuart M. Cahalan ◽  
Pedro J. Gonzalez-Cabrera ◽  
Nhan Nguyen ◽  
Miguel Guerrero ◽  
Elizabeth A. George Cisar ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Sphingosine 1 Phosphate ◽  
Experimental Autoimmune

scholarly journals Treatment With CD52 Antibody Protects Neurons in Experimental Autoimmune Encephalomyelitis Mice During the Recovering Phase

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenlin Hao ◽  
Qinghua Luo ◽  
Michael D. Menger ◽  
Klaus Fassbender ◽  
Yang Liu
Keyword(s):  
Spinal Cord ◽  
T Lymphocytes ◽  
Experimental Autoimmune Encephalomyelitis ◽  
B Lymphocytes ◽  
Neuroprotective Effect ◽  
Recovery Phase ◽  
Conditional Knockout ◽  
Autoimmune Encephalomyelitis ◽  
Inflammatory Infiltration ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic autoimmune disease driven by T and B lymphocytes. The remyelination failure and neurodegeneration results in permanent clinical disability in MS patients. A desirable therapy should not only modulate the immune system, but also promote neuroprotection and remyelination. To investigate the neuroprotective effect of CD52 antibody in MS, both C57BL/6J and SJL mice with experimental autoimmune encephalomyelitis (EAE) were treated with CD52 antibody at the peak of disease. Treatment with CD52 antibody depleted T but not B lymphocytes in the blood, reduced the infiltration of T lymphocytes and microglia/macrophages in the spinal cord. Anti-CD52 therapy attenuated EAE scores during the recovery phase. It protected neurons immediately after treatment (within 4 days) as shown by reducing the accumulation of amyloid precursor proteins. It potentially promoted remyelination as it increased the number of olig2/CC-1-positive mature oligodendrocytes and prevented myelin loss in the following days (e.g., 14 days post treatment). In further experiments, EAE mice with a conditional knockout of BDNF in neurons were administered with CD52 antibodies. Neuronal deficiency of BDNF attenuated the effect of anti-CD52 treatment on reducing EAE scores and inflammatory infiltration but did not affect anti-CD52 treatment-induced improvement of myelin coverage in the spinal cord. In summary, anti-CD52 therapy depletes CD4-positive T lymphocytes, prevents myelin loss and protects neurons in EAE mice. Neuronal BDNF regulates neuroprotective and anti-inflammatory effect of CD52 antibody in EAE mice.

scholarly journals Evaluation of IL-17 Serum Level, Brain Inflammation and Demyelination in Experimental Autoimmune Encephalomyelitis C57BL/6 Mice Model with Different Doses of Myelin Oligodendrocyte Glycoprotein

2019 ◽  
Author(s):  
Mohammad Mehdi Ghorbani ◽  
Touraj Farazmandfar ◽  
Mehrab Nasirikenari ◽  
Saeid Abediankenari ◽  
Ali Meamarian ◽  
...  
Keyword(s):  
Serum Level ◽  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Brain Inflammation ◽  
Therapeutic Interventions ◽  
Nerve Tissue ◽  
Autoimmune Encephalomyelitis ◽  
Wide Range ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system.MS creates a wide range of symptoms with lifelong debilitating consequences. The hallmark of the disease is the inflammation of the nervous system, which can lead to damage to the nerve tissue and loss of function of the neurons. IL-17 has a prominent role in the beginning of inflammatory reactions. Here, we analyzed a mouse model developed using anti-myelin antibodies. This mouse model mimics many symptoms of MS in humans. C57BL/6 mice were randomly divided into five groups. Mice were immunized subcutaneously with 50 μg, 100 μg, 150 μg and 200 μg myelin oligodendrocyte glycoprotein in complete Freund’s adjuvant containing 4 mg/Ml Mycobacterium tuberculosis and two injections of 800 ng of pertussis toxin intraperitoneally, on day 0 and 2 post immunization. Serum level of IL-17 was measured, inflammation and demyelination of brain tissue were also evaluated. Mice with experimental autoimmune encephalomyelitis demonstrated inflammatory cell accumulation, different degrees of demyelination in the brain, and rising levels of serum IL-17 depending on the dose of the anti-myelin antibody. Our study demonstrates that level of IL-17 production is directly associated with inflammation and demyelination. In addition, different degrees of experimental autoimmune encephalomyelitis in mice can be utilized to test a wide range of therapeutic interventions for MS treatment.  

scholarly journals Experimental autoimmune encephalomyelitis from a tissue energy perspective

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1973 ◽  
Author(s):  
Roshni A Desai ◽  
Kenneth J Smith
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Neurological Disorders ◽  
Energy Production ◽  
Therapeutic Strategies ◽  
Cellular Damage ◽  
Nitrogen Species ◽  
Autoimmune Encephalomyelitis ◽  
Wide Range ◽  
Energy Failure ◽  
Experimental Autoimmune

Increasing evidence suggests a key role for tissue energy failure in the pathophysiology of multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE), a commonly used model of MS, have been instrumental in illuminating the mechanisms that may be involved in compromising energy production. In this article, we review recent advances in EAE research focussing on factors that conspire to impair tissue energy metabolism, such as tissue hypoxia, mitochondrial dysfunction, production of reactive oxygen/nitrogen species, and sodium dysregulation, which are directly affected by energy insufficiency, and promote cellular damage. A greater understanding of how inflammation affects tissue energy balance may lead to novel and effective therapeutic strategies that ultimately will benefit not only people affected by MS but also people affected by the wide range of other neurological disorders in which neuroinflammation plays an important role.

Role of Sphingosine 1-Phosphate (S1P) Receptor 1 in Experimental Autoimmune Encephalomyelitis —II

2013 ◽  
Vol 04 (08) ◽  
pp. 638-646 ◽  
Author(s):  
Noriyasu Seki ◽  
Hirotoshi Kataoka ◽  
Kunio Sugahara ◽  
Atsushi Fukunari ◽  
Kenji Chiba
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Experimental Autoimmune

scholarly journals Role of Sphingosine 1-Phosphate (S1P) Receptor 1 in Experimental Autoimmune Encephalomyelitis —I

2013 ◽  
Vol 04 (08) ◽  
pp. 628-637 ◽  
Author(s):  
Noriyasu Seki ◽  
Yasuhiro Maeda ◽  
Hirotoshi Kataoka ◽  
Kunio Sugahara ◽  
Kenji Chiba
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Experimental Autoimmune

scholarly journals BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sofia Fernanda Gonçalves Zorzella-Pezavento ◽  
Clara Pires Fujiara Guerino ◽  
Fernanda Chiuso-Minicucci ◽  
Thais Graziela Donegá França ◽  
Larissa Lumi Watanabe Ishikawa ◽  
...  
Keyword(s):  
Immune Response ◽  
Weight Loss ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Molecular Mimicry ◽  
Clinical Score ◽  
Recovery Phase ◽  
Protective Effects ◽  
Autoimmune Encephalomyelitis ◽  
Inflammatory Infiltration ◽  
Experimental Autoimmune

A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65) after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE) development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γlevels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

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