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Fig. 7 | Acta Neuropathologica Communications

Fig. 7

From: Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis

Fig. 7

EAE in RR-EAE SJL/J mice treated with an LPAR2 agonist. a Plasma concentration time courses and basic pharmacokinetics of the LPAR2 agonist GRI 977143 in SJL/J mice after intraperitoneal injection (i.p.), oral gavage or administration with soaked cornflakes (n = 5–6 per group, i.e. per way of administration). Basic PK parameters were calculated from i.p. data using non-linear, 1-phase decay curve fitting. b Analysis of LPA receptor activation in COS-1 cells transfected with human LPAR1, 2, 3 or 4 along with the promiscuous G-protein alpha subunit (Gα15). Cells were stimulated with the LPAR2 agonist GRI 977143 to confirm LPAR2 specificity. The EC50 was in agreement with the reported EC50 of about 1–3 μM. Data show the mean and sem of 3 replicate analyses. Mock- Gα15 transduced cells were used as controls. c Time courses of clinical EAE scores and body weights of SJL/J mice treated with the LPAR2 agonist GRI 977143 or vehicle perorally starting 3d after immunization (n = 10 per group). AUCs of the scores and body weights were compared with Mann Whitney U test or 2-tailed, unpaired t-test respectively, P < 0.05. d Immunofluorescent analysis of myeloid cell infiltration (CD11b green) into the white matter of the ventral horn in mice treated with vehicle or the LPAR2 agonist, GRI 977143, 36 days after immunization. Neurons were counterstained with NeuN (red) and nuclei are stained with DAP (blue). The white dashed lines show the boundary between the gray and white matter. The dashed yellow rectangles show the areas taken for zoom-in images. Scale bars 50 μm for overview, 25 μm for zoom-in images. Cells were quantified with FIJI ImageJ using images of 4 mice per group. CD11b positive particles were significantly reduced in the white matter of GRI 977143 treated mice, 2-way ANOVA for “site” by “genotype”, posthoc according to Šidák, **P < 0.01 for “genotype”

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