Oligodendrocyte Precursor Cell Transplantation into Organotypic Cerebellar Shiverer Slices: A Model to Study Myelination and Myelin Maintenance

• DOI: 10.1371/journal.pone.0041237
• Publication Date: 2012-07-21T08:33:51Z
• Authors: Jenea M. Bin; Soo Yuen Leong; Sarah-Jane Bull; Jack P. Antel; Timothy E. Kennedy
• Keywords: 0303 health sciences; Science; Q; Primary Cell Culture; Transplantation, Heterologous; R; Myelin Basic Protein; Axons; Rats; Tissue Culture Techniques; Mice; Oligodendroglia; 03 medical and health sciences; Neural Stem Cells; Cerebellum; Medicine; Animals; Humans; Myelin Sheath; Research Article

Current in vitro models to investigate the consequence of oligodendrocyte-specific loss-of-function mutations on myelination are primarily limited co-culture experiments, which do not accurately recapitulate complex vivo environment. Here, we describe development an model and myelin maintenance oligodendrocyte precursor cells transplanted into organotypic cerebellar slice cultures derived from dysmyelinated shiverer mice. Compared neuron-oligodendrocyte co-cultures, slices more closely mimic environment vivo, while utilizing a genetic background that allows for straight-forward identification generated by cells. We show at ultrastructural level wild-type oligodendrocytes is compact terminates cytoplasmic loops form paranodal junctions with axon. This results appropriate sequestering axonal proteins specialized domains surrounding nodes Ranvier. also demonstrate applicability this approach xenograft transplantation rat or human sources. method provides time-efficient cost-effective adjunct conditional knockout mouse lines study mutations. Furthermore, can be readily used assess effect pharmacological manipulations myelin, providing tool better understand develop effective therapeutic strategies treat myelin-related diseases.