Exon Expression Changes in the Spinal Cords of Lewis Rats with Myelin Basic Protein-Induced Experimental Autoimmune Encephalomyelitis (EAE)
Ontology highlight
ABSTRACT: Myelin Basic Protein (MBP) induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat, produces an an acute weakness, or paralysis of the tail and hind limb ataxia ,weakness or paralysis associated with increased permiability of the blood brain barrier, inflammation and demyelination in central nervous system (CNS). Clinical symptoms , ascending weakness or paralysis of the tail followed by the hind limbs and in rare cases the fore limbs occurs 8 and 14 days post immunisation (dpi) and is generally resolved completely by day 20 dpi. We have carried out transcriptome analysis of total RNA from the spinal cords of female Lewis rats at the peak of disease (EAE) and age matched healthy controls to identify exon expression changes associated with the disease. In these data sets we include the exon expression data obtained from total RNA preparations from the spinal cords of female Lewis rats sacrificed at the clinical peak of MBP induced EAE and age matched , untreated, healthy controls. 8 total RNA samples were prepared. A two way ANOVA comparison carried out in Partek Genomics Suite was used to detect differences in exon expression in the spinal cord of female lewis rats with MBP induced EAE and age matched healthy controls.
Project description:Myelin Basic Protein (MBP) induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat, produces an an acute weakness, or paralysis of the tail and hind limb ataxia ,weakness or paralysis associated with increased permiability of the blood brain barrier, inflammation and demyelination in central nervous system (CNS). Clinical symptoms , ascending weakness or paralysis of the tail followed by the hind limbs and in rare cases the fore limbs occurs 8 and 14 days post immunisation (dpi) and is generally resolved completely by day 20 dpi. We have carried out transcriptome analysis of total RNA from the spinal cords of female Lewis rats at the peak of disease (EAE) and age matched healthy controls to identify gene expression changes associated with the disease. In these data sets we include the exon and gene expression data obtained from total RNA preparations from the spinal cords of female Lewis rats sacrificed at the clinical peak of MBP induced EAE and age matched , untreated, healthy controls. This data was used to obtain 2265 mapped IDS wich identified 1190 known genes which were differentially expressed in the spinal cord in EAE compared to healthy animals. 8 total RNA samples were prepared. A two way ANOVA comparison carried out in Partek Genomics Suite was used to detect gene transcripts for which the expression levels varied significantly (un-adjusted p-values M-bM-^IM-$ 0.05) from the healthy controls. 2265 mapped IDs were uploaded to the Ingenuity pathway analysis suite (IPA) where 1190 known genes were identified as being differentially regulated between groups. An FDR M-bM-^IM-$ 5% and fold change limit of +/- 4.0 further refined the data set to identify the 72 most highly and significantly differentially regulated genes in the spinal cord at the clinical peak of disease in MBP induced EAE in the Lewis rat.
Project description:Myelin Basic Protein (MBP) induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat, produces an an acute weakness, or paralysis of the tail and hind limb ataxia ,weakness or paralysis associated with increased permiability of the blood brain barrier, inflammation and demyelination in central nervous system (CNS). Clinical symptoms , ascending weakness or paralysis of the tail followed by the hind limbs and in rare cases the fore limbs occurs 8 and 14 days post immunisation (dpi) and is generally resolved completely by day 20 dpi. We have carried out transcriptome analysis of total RNA from the spinal cords of female Lewis rats at the peak of disease (EAE) and age matched healthy controls to identify exon expression changes associated with the disease. In these data sets we include the exon expression data obtained from total RNA preparations from the spinal cords of female Lewis rats sacrificed at the clinical peak of MBP induced EAE and age matched , untreated, healthy controls.
Project description:Myelin Basic Protein (MBP) induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat, produces an an acute weakness, or paralysis of the tail and hind limb ataxia ,weakness or paralysis associated with increased permiability of the blood brain barrier, inflammation and demyelination in central nervous system (CNS). Clinical symptoms , ascending weakness or paralysis of the tail followed by the hind limbs and in rare cases the fore limbs occurs 8 and 14 days post immunisation (dpi) and is generally resolved completely by day 20 dpi. We have carried out transcriptome analysis of total RNA from the spinal cords of female Lewis rats at the peak of disease (EAE) and age matched healthy controls to identify gene expression changes associated with the disease. In these data sets we include the exon and gene expression data obtained from total RNA preparations from the spinal cords of female Lewis rats sacrificed at the clinical peak of MBP induced EAE and age matched , untreated, healthy controls. This data was used to obtain 2265 mapped IDS wich identified 1190 known genes which were differentially expressed in the spinal cord in EAE compared to healthy animals.
Project description:The possibility of generating neural stem/precursor cells (NPCs) from induced pluripotent stem cells (iPSCs) has opened a new avenue of research that might nurture bench-to bedside translation of novel and more efficient protocols of cell transplantation in central nervous system (CNS) myelin disorders. We have performed the transcriptome analysis in the spinal cord of mice with sham treated Experimental Animal Encephelomyletis (EAE), miPSC-NPC treated EAE mice and naive mice, in order understand the gene expression changes related to the miPSC-NPC treatment.
Project description:We have performed transcriptomic analysis in the spinal cord of experimental autoimmune encephalomyelitis (EAE) mice compared to naive mice at different time intervals in order to observe the gene expression changes within the CNS compartment
Project description:The intention of the study was to examine the spinal cord gene expression at three different EAE disease points and to compare them with three nonimmunised, healthy rats. We immunised female DA rats with recombinant MOG-protein and sacrificed them during the acute phase of EAE defined as the first EAE attack leading to a clinical score of at least three, in the recovery phase in which the rats have begun to gain weight after the acute phase and in the relapsing phase - rats belonging to this group have been sacrificed while they were in the peak of the first relaps. Three healthy control rats, three from the acute phase of EAE (day 11 and 12 after EAE induction), three from the recovery phase (day 13 and 14 after EAE induction) and four rats from the relapsing phase (day 24 and 25 after EAE induction) have been finally sacrificed for the study.
Project description:Microarrays were used to identify genes that were differently expressed in mouse spinal cord as a resut of experimental autoimmune encephalomyelitis (EAE), which is a model for demyelinating disease. Mice were injected with PLP peptide or vechicle.
Project description:Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system (CNS). Ursolic acid (UA) can be used in the MS treatment with anti-inflammatory and neuroprotective activities. However, UA is insoluble in water, which may affect its medication effectiveness. In this study, we evaluated the pharmacological effects of UAOS-Na, a water-soluble UA derivative, on experimental autoimmune encephalomyelitis (EAE) mouse, explored its underlying mechanism, and verified the mechanism by in vitro and in vivo experiments. As we expected, UAOS-Na (30 mg/kg/d) delayed the onset time of EAE from 11.78 days post immunization (dpi) to 14.33 dpi, reduced the incidence from 90.0% to 42.9%, and was more effective than UA. UAOS-Na (60 mg/kg/d) significantly decreased the serum levels of IFN-γ, IL-17A, TNF-α and IL-6, reduced the mononuclear cell infiltration of spinal cord, and inhibited the overexpression of key transcription factors T-bet and ROR-γt of EAE mouse spinal cord and spleen. In addition, UAOS-Na attenuated demyelination and astrogliosis in the CNS of EAE and Cuprizone-induced mice. Mechanically, proteomics showed that 217 differential expression proteins (DEPs) were enriched and 215 were upregulated in EAE mice. After UAOS-Na treatment, 52 DEPs were enriched and 49 were downregulated, and these DEPs were markedly enriched in inositol phosphate metabolism, calcium, sphingolipid, cAMP, and antigen processing and presentation (APP) signaling pathways. Among them, there were few studies on APP signaling pathway related with MS. Therefore, we further investigated the effect of UAOS-Na on APP signaling pathway and found that UAOS-Na downregulated the protein levels of Tapbp and H2-T23 in MHC-I antigen presentation pathway and decreased the proliferation of splenic CD8 T cells, thereby inhibiting the CNS infiltration of CD8 T cells. Together, our findings demonstrated that UAOS-Na have both direct anti-demyelination and anti-inflammation effects. And it could reduce the inflammation of MS by downregulating the expression of Tapbp and H2-T23 in the MHC-I antigen presentation pathway.
Project description:Experimental autoimmune encephalomyelitis (EAE) is a murine model of multiple sclerosis, a chronic neurodegenerative and inflammatory autoimmune condition of the central nervous system (CNS). Pathology is driven by the infiltration of autoreactive CD4+ lymphocytes into the CNS where they attack neuronal sheaths causing ascending paralysis. We used an isotope-coded protein labelling approach to investigate the proteome of CD4+ cells isolated from the spinal cord and brain of mice at various stages of EAE progression in two EAE disease models; PLP139-151-induced relapsing-remitting EAE and MOG35-55-induced chronic EAE, which emulate the two forms of human multiple sclerosis. A total of 1120 proteins were quantified across disease onset, peak-disease and remission phases of disease and of these, 13 up-regulated proteins of interest were identified with functions relating to the regulation of inflammation, leukocyte adhesion and migration, tissue repair and the regulation of transcription/translation. Proteins implicated in processes such as inflammation (S100A4 and S100A9) and tissue repair (Annexin A1), which represent key events during EAE progression were validated by quantitative PCR. This is the first targeted analysis of autoreactive cells purified from the CNS during EAE, highlighting fundamental CD4+ cell-driven processes that occur during the initiation of relapse and remission stages of disease.
Project description:Neural progenitor cells (NPCs) have regenerative capabilities that are activated during inflammation. By measuring the global transcriptome and performing functional studies, we aimed at elucidating if and how NPCs from the non-germinal niche of the spinal cord differ from germinal niche NPCs, here represented by the subventricular zone (SVZ) NPCs. Moreover, we investigated how these cells are affected by chronic inflammation modeled by Experimental Autoimmune Encephalomyelitis (EAE). NPCs were isolated and propagated from the SVZ and cervical, thoracic and caudal regions of the spinal cord from healthy rats and rats subjected to EAE. Using Affymetrix microarray analyses, the global transcriptome was measured in the different NPC populations both in undifferentiated and differentiated cultures. These analyses were paralleled by differentiation studies and quantitative RT-PCR of differentiation-specific genes. In NPCs isolated from healthy rats, transcriptional and functional analyses revealed a higher neurogenic potential in SVZ-derived NPCs compared to spinal cord NPCs. The neurogenicity of spinal cord NPCs was increased by exposure to the inflammatory environment. Concurrently, their gliogenicity was decreased which was supported by a decreased expression of glial differentiation signature genes and related signaling pathways. Differentiation analyses showed that spinal cord NPCs from EAE rats generated fewer oligodendrocytes and astrocytes than NPCs isolated from healthy controls. 54 samples were analysed. The transcriptome of NPCs isolated from healthy rats or rats with EAE was measured. The NPCs were isolated from the SVZ and the cervical, thoracic and caudal parts of the spinal cord. Pair wise student t-test analysis between the 3 EAE replicates and naive controls for each respective tissue type was performed. Genes with a signal value above the cut-off of 50 and with FDR M-bM-^IM-$ 5% and a foldchange of M-bM-^IM-%1.2 or M-bM-^IM-$-1.2 were selected for further analysis.