The Research Of Therapeutical Effect And Mechanism About Progesterone Treating The Experimental Allergic Encephalomyelitis

Multiple sclerosis is one kind of central nervous system(CNS) demyelinating disearses, which typical example course is release- relapse and aggravation in progress. The pathogenesy is not clear and there is not active treatment. After demyelination of CNS, the spontaneous remyelination is not sufficient. So that there are no myelin to encapselate naked axon. Finaly, the axon are damaged secondary. Above all, it is active treatment to promote the remyelination of MS. Progesterone is one of progestins which are clinically used widely. It is cheap and gained easily. It has been confirmed that progesterone can promote the differentiation of oligodendrocyte, the myelination and the remyelination in CNS.Myelin basic protein(MBP) protein is a main composition of myelin which is importment for maintaining the membrane layer of myelin. MBP liberates from myelin when myelin has been destoried. The impairment of myelin in CNS can be conclude by detect the MBP protein in blood and cerebrospinal fluid. The PDGF-αR is an early and importment marker of oligodendrocyte precursor cells. With the differentiation, the PDGF-αR disapears. The Olig1 which expresses in oligodendrocyte cells is one of basic helix-loop-helix(bHLH). It can increase the expression of MBP,myelin proteolipid protein(PLP1),myelin associated glucoprotein (MAG).at same time, it can suppress the expression of GFAP. Perhaps, the Olig1 regulates the remyelination only. Because of the low Olig1 protein, the remyelination of older rats were sufficient by immunohistochemistry(IHC). Resently, the translocation of Olig1 protein in myelination and remyelination was reported. Only in nucleus, the Olig1 protein can be active. In some Olig1+ cell of MS brain, the Olig1 protein located in cytoplasmic. Those cells can't differentiate to mature oligodendrocyte to remyelinate axon. The translocation of Olig1 protein may be a key factor of remyelination.The experimental allergic encephalomyelitis(EAE) is a good animal modle. In this study, the EAE rats were treated with progesterone. The therapeutic efficacy was judgement by nerve function score, staining of myelin and electron microscope et al. Meanshile, the machanism was researched initially by IHC,Western Blot, real time RT-PCR, et al. There are some revelations.Firstly, there was no obvious differention in the nerve function score between treating and control group. The nerve function score was used usually in similar researchs. But it is too rough. So according to the score, it is not concluded that the progesterone can lessen the symptom of EAE rats. But the density of normal myelin in treating group was higher than that in control group by electron microscope. The gray scale of normal myelin in treating group was higher and cataplasis myelin in treating myelin was lower than that in control by LFB and marchi's staining. So it can be concluded that the progesterone can promote the remyelination of EAE rats.Secondly, PDGF-αR expressing cells were found in the forebrain and midbrain, but not in the cerebellum and brainstem. Based on the number of cell processes and branches, the main distinction among PDGF-αR expressing cells in different regions, the cells were classified into 3 categories, ie., type I to type III. From type I to type III, number of processes increased gradually. The OB and hippocampus which were I type cells mainly may be the germinal areas of PDGF-αR expressing cells in the adult rat brain. It may be relatively difficult for myelination and remyelination to occur in the cerebellum and brainstem resulting in a high susceptibility of the cerebellum and brainstem to chronic damages.Thirdly, it is about the mechanism. 1)The gray scale of myelin debris in treating group was lower than that in control. 2)The MBP protein in treating group was lower than that in control also. 3)In early stage, the PDGF-αR protein didn't change in treating and control groups. After this, it decreased . But in 25th, the PDGF-αR protein came back to the level of normal rats. There was no difference among treating and control groups. 4)The Olig1mRNA of EAE rat was not different than that of normal all course. 5)The quantity of Olig1+ cells in which the olig1 protein located in nucleus in treating group was higher than that in control. Those results suggest that 1)the progesterone can decrease the myelin debris which come from the demyelination. So it can decrease the inhibitory of myelin debris to remyelination. 2)The progesterone can stabilize the structure of myelin's membrane layer. 3)The progesterone can promote the OPCs differentiating to mature oligodendrocyte to remyelination. 4)The progesterone can not in creasethe Olig1mRNA in EAE rats. 5)But it can promote the Olig1 protein translocating from cytoplasm to nucleus.Above all, the progesterone may be an active drug. The translocation of Olig1 protein from cytoplasm to nucleus may be a action point of new drugs for demyelination diseases.