Inhibition of neurogenesis in a case of Marburg variant multiple sclerosis

Abstract

Introduction: Neural stem cells (NSC) are located essentially in the subventricular zone (SVZ), subgranular zone (SGZ), and along the central canal of the spinal cord. These cells can proliferate in vitro and differentiate into neurons, oligodendrocytes, and astroglia, thus contributing to repair in multiple sclerosis (MS). We conducted a pathological study to analyse neurogenic response in a patient with Marburg variant MS.

Methods: We present the case of a 27-year-old immunocompetent patient with Marburg variant MS, a fulminant form of the disease. The condition lasted 20 days. Diagnosis was based on clinical symptoms and MRI showed demyelinating lesions located in subependymal areas and histopathological findings. Neurogenic niches (SVZ and dentate gyrus) were analysed by confocal microscopy using markers of proliferation (Ki-67, PCNA), neuroblasts (PSA-NCAM, DCX, Tuj1), stem cells (Nestin, GFAPδ, SOX2, PAX6, Musashi), astrocytes (GFAP, AQ4), oligodendrocytes (NG2, Olig), microglia and cell infiltrates (IBA-1, CD68, MHCII), and cell death (TUNEL).

Results: Expression of the markers GFAPδ, SOX2, and PAX6 in NSC was found to be very low. Likewise, markers of proliferation (Ki-67) and intermediate precursors (NG2) were also reduced. This lack of markers of the first stages of cell differentiation means that neurogenesis is inhibited even in very early stages of the disease.

Conclusion: Inhibition of neurogenesis in our patient, which cannot be explained by the fulminant nature of his symptoms, may be related to inflammation and immune response. This finding may further our knowledge of repair mechanisms in MS.

Keywords: Adult neurogenesis; Marburg variant; Multiple sclerosis; SVZ.