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 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

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 Siponimod Inhibits the Formation of Meningeal Ectopic Lymphoid Tissue in Experimental Autoimmune Encephalomyelitis

2021 ◽  
Vol 9 (1) ◽  
pp. e1117
Author(s):  
Rosa Margareta Brand ◽  
Jolien Diddens ◽  
Verena Friedrich ◽  
Monika Pfaller ◽  
Helena Radbruch ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Lymphoid Tissue ◽  
Disease Onset ◽  
Autoimmune Encephalomyelitis ◽  
Disease Treatment ◽  
Beneficial Effects ◽  
Sphingosine 1 Phosphate ◽  
Inflammatory Infiltrates ◽  
Histology And Immunohistochemistry ◽  
Experimental Autoimmune

Background and ObjectivesTo investigate whether the formation or retention of meningeal ectopic lymphoid tissue (mELT) can be inhibited by the sphingosine 1-phosphate receptor 1,5 modulator siponimod (BAF312) in a murine model of multiple sclerosis (MS).MethodsA murine spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model, featuring meningeal inflammatory infiltrates resembling those in MS, was used. To prevent or treat EAE, siponimod was administered daily starting either before EAE onset or at peak of disease. The extent and cellular composition of mELT, the spinal cord parenchyma, and the spleen was assessed by histology and immunohistochemistry.ResultsSiponimod, when applied before disease onset, ameliorated EAE. This effect was also present, although less prominent, when treatment started at peak of disease. Treatment with siponimod resulted in a strong reduction of the extent of mELT in both treatment paradigms. Both B and T cells were diminished in the meningeal compartment.DiscussionBeneficial effects on the disease course correlated with a reduction in mELT, suggesting that inhibition of mELT may be an additional mechanism of action of siponimod in the treatment of EAE. Further studies are needed to establish causality and confirm this observation in MS.

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.

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