ISDN2012_0282: Variation in neural physiology and anatomy due to diet related factors as a possible cue to neurodegeneration

S. Sekizar 1,2,3, K. Mannioui 1,2,3, A. Desmazieres 1,2,3, J.L.Thomas 1,2,3,4, B. Zonta 5, P.J. Brophy 5, B. Zalc 1,2,3,4 1 Université Pierre et Marie Curie-Paris 6; Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière, France 2 UMRS 975, Paris 75013, France 3 CNRS UMR 7225, France 4 AP-HP, Hôpital de la Pitié Salpêtrière, France 5 Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, UK Myelination process allows a rapid and efficient conduction of action potential along axons. Oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS) are two types of myelinating glial cells. These glial cells enwrap the axon in segments alternating with the nodes of Ranvier. The nodes correspond to non-myelinated axonal domains with high density of voltage gated ion channels, which allow rapid propagation of action potentials. These channels form molecular complexes with cell adhesion and scaffolding molecules involved in nodal assembly and stabilization. During development the axoglial interaction facilitates recruitment and clustering of molecules to the node and surrounding domains, namely paranodes and juxta paranodes. The dynamic changes that occur during myelination and remyelination have not yet been investigated in vivo in real time. Our aim is to investigate these dynamic changes in vivo using Xenopus as a model. The external development of embryos and transparency of tadpoles makes it a suitable model for live imaging. The myelin structure in Xenopus has been shown to be very similar to rodents. We have established that nodal organization in Xenopus is also close to rodents, using immunohistochemistry and bioinformatic approach. Our approach is to develop transgenic Xenopus lines expressing various proteins coupled to fluorescent markers to follow myelination and dynamic changes that occur at the nodes of Ranvier during development and remyelination. Our laboratory has already generated a transgenic Xenopus with GFP fused to proteolipid protein (PLP) to visualize myelination. We are now in the process of generating transgenic Xenopus where neuronal isoform of Neurofascin (Nfasc), a cell adhesion molecule of the L1CAM family shown to be necessary for assembly of nodes of Ranvier, is expressed in fusion with a fluorescent protein. This transgenic would allow us to visualize the dynamic changes during myelination.