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Discoidin Domain Receptor 1, a Tyrosine Kinase Receptor, is Upregulated in an Experimental Model of Remyelination and During Oligodendrocyte Differentiation In Vitro

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Abstract

The discoidin domain receptor (DDR1) is highly expressed in oligodendrocytes during the neurodevelopmental myelination process and is genetically associated to schizophrenia. In this study, we aimed to further assess the involvement of DDR1 in both remyelination and oligodendrocyte differentiation. In the mouse model of demyelination–remyelination induced by oral administration of cuprizone, in situ hybridization showed an upregulation of the DDR1 gene in three different white matter areas (corpus callosum, dorsal fornix, and external capsule) during the remyelination period. Moreover, real time reverse transcriptase polymerase chain reaction showed that the increase in DDR1 messenger RNA (mRNA) was strongly correlated with the number of DDR1-positive cells in the corpus callosum (Spearman coefficient = 0.987, P = 0.013). Cells positive for DDR1 mRNA were also positive for oligodendrocyte markers (OLIG2, carnosine, and APC) but not for markers of oligodendrocyte precursors (NG2), myelin markers (CNPase), microglia (CD11b), or reactive glia (GFAP). Differentiation of a human oligodendroglial cell line, HOG16, was associated with an increase in mRNA expression of DDR1 and several myelin proteins (MBP and MOBP) but not other proteins (APC and CNPase). Here, we demonstrate that DDR1 is upregulated in vitro and in vivo when oligodendrocyte myelinating machinery is activated. Further studies are needed to identify the specific molecular pathway.

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Acknowledgments

This work was supported by the Spanish Ministry of Health (Fondo the investigación Sanitaria PI02/0498) and the Stanely Research Institute (#03R-392 and #05R-896).

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Authors and Affiliations

  1. Unitat de Psiquiatria i Psicologia Mèdica, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, C/Sant Llorenç 21, 43201, Reus, Spain

    Neus Franco-Pons, Jordi Tomàs, Bárbara Roig, Lourdes Martorell & Elisabet Vilella

  2. Departament de Formació i Investigació, Hospital Psiquiàtric Universitari Institut Pere Mata, Ctra. de l’Institut Pere Mata s/n, 43206, Reus, Spain

    Neus Franco-Pons, Jordi Tomàs, Bárbara Roig, Lourdes Martorell & Elisabet Vilella

  3. Departament de Biologia Cel·lular, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08034, Barcelona, Spain

    Carme Auladell

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  1. Neus Franco-Pons
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  2. Jordi Tomàs
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Correspondence to Elisabet Vilella.

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Franco-Pons, N., Tomàs, J., Roig, B. et al. Discoidin Domain Receptor 1, a Tyrosine Kinase Receptor, is Upregulated in an Experimental Model of Remyelination and During Oligodendrocyte Differentiation In Vitro. J Mol Neurosci 38, 2–11 (2009). https://doi.org/10.1007/s12031-008-9151-x

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