Defining the role of NG2-expressing cells in experimental models of multiple sclerosis. A biofunctional analysis of the neurovascular unit in wild type and NG2 null mice

• DOI: 10.1371/journal.pone.0213508
• Publication Date: 2019-03-14T18:35:15Z
• Authors: Francesco Girolamo; Mariella Errede; Giovanna Longo; Tiziana Annese; Carlotta Alias; Giovanni Ferrara; Sara Morando; Maria Trojano; Nicole Kerlero de...; Antonio Uccelli; Daniela Virgintino
• Keywords: Occludin

During experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis associated with blood-brain barrier (BBB) disruption, oligodendrocyte precursor cells (OPCs) overexpress proteoglycan nerve/glial antigen 2 (NG2), proliferate, and make contacts the microvessel wall. To explore whether OPCs may actually be recruited within neurovascular unit (NVU), de facto intervening in its cellular molecular composition, we quantified by immunoconfocal morphometry presence of contact brain microvessels, during postnatal cerebral cortex vascularization at day 6, wild-type (WT) NG2 knock-out (NG2KO) mice, adult naïve EAE-affected WT NG2KO mice. As observed mice development, higher number juxtavascular perivascular was revealed EAE compared to In were mostly microvessels that showed altered claudin-5 occludin tight junction (TJ) staining patterns leakage. contrast, which did not show any significant increase vessel-associated OPCs, seemed retain better preserved TJs BBB integrity. expected, absence NG2, both pericytes, led reduced content vessel basal lamina molecules, laminin, collagen VI, IV. addition, analysis major ligand/receptor systems known promote OPC proliferation migration indicated vascular endothelial growth factor A (VEGF-A), platelet-derived factor-AA (PDGF-AA), transforming factor-β (TGF-β) molecules most likely involved recruitment EAE. These results confirmed real time-PCR Fgf2, Pdgfa Tgfb expression on isolated dual RNAscope-immunohistochemistry/in situ hybridization (IHC/ISH), detected Vegfa Vegfr2 transcripts sections. Overall, this study suggests virtue their developmental arrangement response neuroinflammation factors, could integrated among classical NVU cell components. Moreover, synchronized activation pericytes development dysfunction, points as key regulator interactions.