Gene Expression Profile In MS And EAE With Gene Chips And The PET Study In MS

Objective It is believed that Multiple Sclerosis( MS ) is caused by an aberrant immune response against one or more CNS myeline proteins that occurs in genetically susceptiple individuals. Experimental autoimmune encephalomyelitis(EAE) has long been used as an animal model for human MS. The advent of genomic screening has permitted a comprehensive approach to the genetic susceptibility of MS. (1) To construct the immune genes expression profile database of MS and to screen the high immune-related candidate genes by using microarray analysis. (2)To construct the genes expression profile database of experimental autoimmune encephalomyelitis(EAE) mice model induced by Myelin proteolipid protein (PLP)139-151 peptide and to screen the high candidate genes with microarray analysis.(S) To evaluate the application of 18F-FDG PET and compare with MRI tests to pathological examinations in multiple sclerosis, especially in demyelinating pseudotumor and the course of the disease.Methods (1) Polymerase chain reaction (PCR) products on behalf of 484 immune-related genes from mixed tissue library were assembled on the modified Oako glass slide. The general RNA from MS patients and normal persons lymphocytes was transcripted to cDNA by RT-PCR and labelled with cy-3 and cy-5. The two probes were mixed and hybridized with the above mentioned gene chips. Scan array 4000 was used for scanning the hybridizing signals and GenePixProS.O for date analysis. (2) PCR products on behalf of 4096 genes from mixed mice tissue library were assembled on the modified Oako glass slide. The general RNA from EAE mice model and normal mice head was transcripted to cDNA by RT-PCR and labelled with cy-3 and cy-5. The two probes were mixed and hybridized with the above mentioned gene chips. Scan array 4000 was used for scanning the hybridizing signals and GenePixPro3.0 for date analysis. (3) Two patients clinically verified multiple sclerosis, had PET and MRI tests performed andfollowed with pathologic examination for intra cranial sclerosis and disease staging.Results (1)Of the total 484 double genes monitored, 22 genes of group one showed changes in expression level of the ratio outside 0.5 and 2, 27 genes differ in group 2, 72 genes change in group 3.With the same consistent Gene ID of the double genes, the group one was 6, the group tow was 9 and the group three was 30. (2)Of the total 4096 genes monitored, 43 genes in group one showed changes in expression level of the ratio outside 0.5 and 2, 30 genes differ in group two, 176 genes change in group three, 76 in group four, 294 in group five and 129 in group six. (3) MR imaging demonstrated low signal on T1-weight and high signal on T2-weight. PET showed mild increase of oxygen metabolism in the right parietal lobe and left cerebellum in case 1 and general reduction of oxygen metabolism in the left parietal, temporal and occipital cortex in case 2. On the pathological examination, CD68 was stained for a mass of macrophages around the vessel. HE stained for gelatinous fiber hyperplasia, perivascular cuffing of lymphocyte infiltration. Luxol fast blue stain showed demyelination.Conclusions (1) These results show that the different expression of immune-related genes might occur between MS patients and normal persons. It might also afford a view of the changes that these genes should be probably related to the occurrence, development or progress of MS. The cell immune-related genes might be the important and most immune-related genes involved in MS pathogenesis. The results suggest the deeper insights into the mechanism, relapsing and treatment of MS. (2) The results showed the consistent different genes expression throughout the EAE mice model. The genes related to immune, cell structure, cell cycle, ion chanal,signal transduction, protein synthesis and metabolism involved in EAE pathogenesis. The results provide deeper insights into the mechanism of EAE and Multiple Sclerosis.(3) PET will help to definite the course of the lesion in the white matter and differentiate the demyelinating...