Research projects

The first objective of this project was to compare the mobilization of NG2-glial cells in multiple sclerosis (MS), using experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ) models induced in C57BL/6 mice. This goal was addressed by combining the StarTrack clonal analysis tool and the induction of
experimental MS models. E14 neural progenitors were labeled with StarTrack and their NG2-glial progeny were analyzed clonally, at the peak of disease. Our results show, before the induction of EAE in the cortex and corpus callosum, a clonal and heterogeneous response of the NG2 glia, both in the proliferation capacity and in the morphological change towards hypertrophy of these cells. Further analysis of the morphology of NG2 glia in the cortex and corpus callosum (CC) showed that under physiological conditions there are at least three groups of NG2 glia according to their morphology: one both in the CC and in layer I of the cortex, another in the upper cortical layers and the third in the lower cortical layers. 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 this, a comparison of the proteomic profile was first made between different regions (cortex and spinal cord) of mice with EAE and CPZ, with respect to control animals. Our results show regional differences in the regional glial response in both MS models, identifying only one common protein altered in the two regions of EAE and CPZ: Orosomucoid-1 (Orm1), also known as Alpha-1-acid glycoprotein 1 (AGP1). This protein has previously been described in serum and in cerebrospinal fluid in patients with MS, however, with this work we have described for the first time Orm1 alterations in the cortex of EAE and CPZ mice, and its presence in the brain of patients with RRMS, reflecting the importance of these changes in MS.