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Progression of different forms of multiple sclerosis related to the stem/progenitor cells potential

19th national competition for scientific and technical research

Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS): Molecular Etiology and Novel Treatments

Senior Researcher : Laura López Mascaraque

Research Centre or Institution : Instituto Cajal. CSIC. Madrid.

Abstract

The first objective of this project was to compare the mobilization of NG2-glial cells in multiplesclerosis (MS), using experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ) models induced in C57BL/6 mice. To this end, we combined the StarTrack clonal analysis tool in both experimental MS models. Neural E14 progenitors were targeted using the StarTrack mix, to evaluate the clonal response of their derived NG2-glia progeny to brain damage at the peak of the disease in both models: EAE mice 15 days postinduction (dPI), and CPZ induced mice 35 dPI. Our results showed a heterogenic and clonal response of NG2-glia to the EAE induction in both cortex and the corpus callosum. This heterogeneous NG2-glia response was evident in both clonal proliferation and in their morphological change towards hypertrophy. 
 
OA deeper analysis of NG2-glia morphology throughout the cortex was made in order to understand their morphological change due to inflammation, based on different morphometric parameters. We revealed that in physiological conditions there are at least three NG2-glia clusters: the first in both the corpus callosum (CC) and layer I, the second in the upper cortical layers, and the third one in lower cortical layers. Moreover, in response to EAE and CPZ, NG2-glia of the corpus callosum modified their morphology in a more significant way than in lower cortical layers cells.

The second objective was to analyze the cell response in postmortem human brains of the relapsing remitting (RRMS) and the primary progressive multiple sclerosis (PPMS). To address it, first we are performing a proteomic analysis of the cortex and the spinal cord (SC) in both experimental models. This will help us understand the pathophysiology of MS, to find proteins altered in the disease that may act as new targets for future therapeutic treatments. The expression of these altered proteins will be verified in the human tissue in order to characterize what type of cells express them in response to MS disease. For this, the human tissue was requested to the Netherlands Brain Bank, Amsterdam, and the immunohistochemical staining are currently made on control human tissue.

 

Scientific Production
 
Magazine Articles 5
Communications at national conferences 12
Communications at international conferences 9

 

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