Inhibition of adult neurogenesis in a Marburg´s variant of multiple sclerosis (P4.028)

Objective: To study the neurogenesis in the Marburg´s variant of multiple sclerosis Background: Under pathological conditions the subventricular zone (SVZ) and the dentate gyrus of the hippocampus (DG) modify their activity and morphology. There are very few studies in multiple sclerosis about the differentiation and proliferation of oligodendrocyte precursor cells in both areas. Methods: We study the case of a 27 years old immunocompetent patient with a fulminant Marburg´s disease. The disease duration was 20 days. The patient´s postmorten sample was studied using conventional histological dying (H/E, luxol fast blue and oil-red stain) and immunochemical and immunofluorescence techniques.. SVZ and DG were analyzed with confocal microscopy using markers for proliferation (Ki67, PCNA), neuroblasts (TUJ1), stem cells (GFAPd, SOX2, PAX6, Musashi), astrocytes (GFAP, AQ4), oligodendrocytes (NG2, Olig), microglia and cellular infiltrates (IBA-1, CD68 , MHCII) and cellular death (Tunel). Results: The neuropathological study showed extensive areas of inflammation with severe destruction of myelin and a generalized vasogenic edema. We found a 10-fold decrease in the number of Ki-67+ cells and PCNA in the SVZ in comparison with healthy controls, indicating an almost absent cell proliferation. GFAPδ (0.215±0.015 cells per mm2), PAX6 (8.41±0.83 cells per mm2) and SOX2 were significantly reduced in SVZ and DG. NG2 positive cells were decreased in corpus callosum. A very low expression of Olig and NG2 and a strong increase of inflammatory cells (IBA-1 +, CD68+, MHCII+) in lesions were found. Glial stem cells (musashi positive) were not found in DG and SVZ Conclusions: Cell proliferation was drastically decreased in the SVZ and in DG. Neurogenesis was not found despite the strong inflammatory response and the high level of cellular death associated to the pathology. The fulminant course of the case could be explained by the reduction of the neurogenesis and no differentiation of oligodendrocyte precursor cells. Disclosure: Dr. Oreja-Guevara has received research support from Biogen Idec and Merck Serono. Dr. Garcia-Lopez has nothing to disclose. Dr. Sanchez-Sanchez has nothing to disclose. Dr. Orviz-Garcia has nothing to disclose. Dr. Gonzalez-Suarez has nothing to disclose. Dr. Rabano has nothing to disclose. Dr. Gomez-Pinedo has nothing to disclose. Dr. Matias-Guiu has received personal compensation for activities with Jannsen Pharmaceuticals and Biogen Idec as a consultant and/or speaker.