Lysophosphatidic Acid can Support the Formation of

Authors: Luciana Nogaroli Larra M Yuelling Jameel Dennis Karen Gorse Shawn G Payne Babette Fuss

Publish Date: 2008/07/02

Volume: 34, Issue: 1, Pages: 182-193

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Abstract

During development differentiating oligodendrocytes progress in distinct maturation steps from premyelinating to myelinating cells Such maturing oligodendrocytes express both the receptors mediating signaling via extracellular lysophosphatidic acid LPA and the major enzyme generating extracellular LPA namely phosphodiesteraseIα/autotaxin PDIα/ATX However the biological role of extracellular LPA during the maturation of differentiating oligodendrocytes is currently unclear Here we demonstrate that application of exogenous LPA induced an increase in the area occupied by the oligodendrocytes’ process network but only when PDIα/ATX expression was downregulated This increase in network area was caused primarily by the formation of membranous structures In addition LPA increased the number of cells positive for myelin basic protein MBP This effect was associated by an increase in the mRNA levels coding for MBP but not myelin oligodendrocyte glycoprotein MOG Taken together these data suggest that LPA may play a crucial role in regulating the later stages of oligodendrocyte maturationThe authors thank S Pfeiffer for the hybridoma cell line O4 and S Spiegel for helpful discussions and comments Confocal and fluorescent microscopy was performed at VCU’s Department of Neurobiology and Anatomy Microscopy Facility which was supported in part through NIHNINDS Center Core grant 5P30NS047463 This work was supported by grants from the National Institute of Health BF the National Multiple Sclerosis Society BF a postdoctoral fellowship award from the National Multiple Sclerosis Society JD and a predoctoral fellowship award from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior of the Brazilian Ministry of Education LN

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