Unknown,Transcriptomics,Genomics,Proteomics

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Exon Expression Changes in the Spinal Cords of Lewis Rats with Myelin Basic Protein-Induced Experimental Autoimmune Encephalomyelitis (EAE)

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.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Hayley Inglis

PROVIDER: E-GEOD-39120 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.

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Dataset Information

Exon Expression Changes in the Spinal Cords of Lewis Rats with Myelin Basic Protein-Induced Experimental Autoimmune Encephalomyelitis (EAE)

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