Project description:Vaccination with naked DNA encoding myelin basic protein represents a promising therapeutic strategy in multiple sclerosis (MS). In this study, we assessed the potential of vaccination with a DNA construct coding for the myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in MS, to induce tolerance and protect against experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrated that MOG-DNA vaccination reduced the clinical and histopathological signs of EAE when administered in both prophylactic and therapeutic settings. Further mechanistic experiments revealed that the protective effects of MOG-DNA vaccines were associated with a reduction of antigen-specific Th1 and Th17 cellular immune responses and expansion of regulatory T cells in periphery, and up-regulation in the central nervous system of genes encoding neurotrophic factors and proteins involved in remyelination. These results may set the rationale for the use of MOG-based DNA vaccines to induce tolerance in MS patients. We analyzed brain and spinal cord samples from five treated and five control mice
Project description:Vaccination with naked DNA encoding myelin basic protein represents a promising therapeutic strategy in multiple sclerosis (MS). In this study, we assessed the potential of vaccination with a DNA construct coding for the myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in MS, to induce tolerance and protect against experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrated that MOG-DNA vaccination reduced the clinical and histopathological signs of EAE when administered in both prophylactic and therapeutic settings. Further mechanistic experiments revealed that the protective effects of MOG-DNA vaccines were associated with a reduction of antigen-specific Th1 and Th17 cellular immune responses and expansion of regulatory T cells in periphery, and up-regulation in the central nervous system of genes encoding neurotrophic factors and proteins involved in remyelination. These results may set the rationale for the use of MOG-based DNA vaccines to induce tolerance in MS patients.
Project description:Genetic opticospinal EAE (OSE) and MOG-induced EAE (MOG-EAE) are two experimental autoimmune encephalomyelitis (EAE) mouse models of human multiple sclerosis. For the OSE model, double-transgenic 2D2 (TCRMOG) x IgHMOG mice were used. For MOG-EAE, wildtype C57BL/6 mice were immunized with a MOG peptide consisting of the amino acids 35-55, administered in complete Freund’s adjuvant containing 5mg / ml Mycobacterium tuberculosi. The severity of EAE was rated on the scale 0: healthy animal; 1: animal with a flaccid tail; [...]; 4: animal with both hind legs paralyzed. The case groups in the experiment were: OSE1: OSE with disease score 1; OSE4: OSE with disease score 4; MOG4: MOG-EAE injected with both MOG and adjuvant, with disease score 4. The control groups in the experiment were: OSE0: OSE with disease score 0; CFA: C57BL/6 mice injected only with adjuvant (no MOG); WT: Wildtype C57BL/6 mice. The aim of the experiment was to assess gene expression differences 1) between OSE4 and OSE0, 2) between OSE1 and OSE0, and 3) between MOG4 and CFA. For control, WT was compared to OSE0 and CFA. Subsequently, differentially expressed transcripts were compared, first, between the OSE4 vs. OSE0 and the MOG4 vs. CFA contrasts (different EAE models) and, second, between the OSE4 vs. OSE0 and the OSE1 vs. OSE0 contrasts (different EAE severity).
Project description:Experimental autoimmune encephalomyelitis (EAE)-susceptible DA and EAE-resistant PVG rats were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce an autoimmune response.<br>Seven days later draining inguinal lymph nodes were removed. 2 conditions were examined: 'ex vivo' and 'MOG restimulated', which involved 24hrs of incubation with an encephalogenic MOG 91-108 peptide.
Project description:Experimental autoimmune encephalomyelitis (EAE)-susceptible DA and EAE-resistant congenic R23 rats were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce an autoimmune response.<br><br>Seven days later draining inguinal lymph nodes were removed. 2 conditions were examined: 'ex vivo' and 'MOG restimulated', which involved 24hrs of incubation with an encephalogenic MOG 91-108 peptide.<br><br>
Project description:We identified that AIM2 protected against MOG-induced EAE, and AIM2 deficiency in microglia promoted the development of EAE. The purpose of this experiment was to identify how AIM2 protected against MOG-induced EAE.
Project description:Purpose: We used RNA sequencing to investigate the effect of needling treatments on GB20 acupoint in EAE model mice Methods: Retinal mRNA profiles of 13-week-old female sham control mice (SHAM), EAE model mice with MOG injection (MOG), EAE model mice with needling treatment at acupoint GB20 (GB20) and its control acupoint GV16 (GV16) were generated by deep sequencing, in triplicate, using Illumina Hiseq platform. The sequence reads that passed quality filters were analyzed with DESeq2 R package to identify differently expressed genes with padj<0.05. Results: RNA-seq identified total 234 DEGs, with 100 genes upregulated and 134 genes downregulated, comparing MOG group with SHAM group.Further analysis revealed that, among the MOG injection induced 100 up-regulated DEGs, 24 DEGs were reversed and significantly down-regulated by GB20 treatment, while 14 were reversed and significantly down-regulated by GV16 treatment. However, 12 of the 14 reversed DEGs of GV16 treatment were already included in the 24 DEGs of GB20. The left 2 DEGs specific to GV16 treatment were Gfap (glial fibrillary acidic protein) and Fgf2 (fibroblast growth factor 2). As to the MOG injection induced 134 down-regulated DEGs, 12 DEGs were reversed and significantly up-regulated by GB20 treatment, while only 3 DEGs were reversed and significantly up-regulated by GV16 control treatment, and all the 3 DEGs were included in the 12 DEGs of GB20 treatment. Conclusions: Our research first reported that needling treatment on GB20 had regulation effects on retinal transcriptome of EAE model mice, indicating potential way of therapy for treatment of optic neuritis.
Project description:Neuroprotective effects of NDP-MSH. We have characterized the signaling down-stream of melanocortin-1 receptor ligation to identify pathways mediating neuroprotective effects of NDP-MSH using transcriptional profiling. In this data set we included the expression data obtained from mouse brain tissue (MOG-immunized wild-type or C57BL/6Je/e mice at disease maximum, d14 after immunization). The data were used to obtain differentially regulated genes in wild-type or C57BL/6Je/e mice upon systemic NDP-MSH treatment.
Project description:The aim of the experiment is to characterize the genetics and mechanisms of the inflammatory response after induction of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, by studying the genome wide expression in the spleen in late disease. A backcross was created between EAE-susceptible DA and EAE-resistant PVG rats. At day 35 after induction of EAE with myelin oligodendrocyte glycoprotein (MOG) in these rats, spleens were taken for transcriptional profiling.
Project description:To evaluate the therapeutic potential of NLP(ITE+MOG) in a mouse model of secondary progressive multiple sclerosis, we induced EAE in NOD mice and initiated weekly treatment with nanoliposomes beginning at 35 days post immunization during the chronic phase of disease. NLP(ITE+MOG) administration ameliorated EAE, and the transcriptional analysis of CNS-resident astrocytes, microglia and monocytes revealed decreased expression of genes associated with pro-inflammatory responses and neurodegeneration.
