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ABSTRACT: Receptor protein tyrosine phosphatase sigma (RPTPsigma) plays a role in inhibiting axon growth during development. It has also been shown to slow axon regeneration after peripheral nerve injury and inhibit axon regeneration in the optic nerve. Here, we assessed the ability of the corticospinal tract (CST) axons to regenerate after spinal hemisection and contusion injury in RPTPsigma deficient (RPTPsigma(-/-)) mice. We show that damaged CST fibers in RPTPsigma(-/-) mice regenerate and appear to extend for long distances after a dorsal hemisection or contusion injury of the thoracic spinal cord. In contrast, no long distance axon regeneration of CST fibers is seen after similar lesions in wild-type mice. In vitro experiments indicate that cerebellar granule neurons from RPTPsigma(-/-) mice have reduced sensitivity to the inhibitory effects of chondroitin sulfate proteoglycan (CSPG) substrate, but not myelin, which may contribute to the growth of CST axons across the CSPG-rich glial scar. Our data suggest that RPTPsigma may function to prevent axonal growth after injury in the adult mammalian spinal cord and could be a target for promoting long distance regeneration after spinal cord injury.
Glia 09/2009; 58(4):423-33. · 4.82 Impact Factor
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ABSTRACT: The morphogenesis of oligodendrocytes is essential for central nervous system myelin formation and the rapid propagation of axon potentials through saltatory conduction. However, the discrete cellular events involved in the three-dimensional maturation of oligodendrocytes remain to be fully described. To address this, we followed the developmental stages of oligodendrocytes in mouse organotypic hippocampal slice cultures for 7-60 days using viral-mediated gene delivery of membrane-targeted fluorescent proteins. Using static and time-lapse confocal imaging, we find that postmigratory NG2-expressing cells exhibit slow anatomical reorganization over the course of hours. This is in direct contrast to oligodendrocytes that take on a promyelinating and transitional phenotype, which display a more complex morphology and undergo dramatic actin-dependent structural remodeling over just minutes. More mature myelinating oligodendrocytes, which have pruned most of their processes, still retain some local remodeling behavior at developing internodes, but in general, revert to a relatively stable state. Our findings provide a detailed characterization of cellular events that help shape oligodendrocyte morphology and likely participate in neuron-glial cell interactions and the process of myelination.
Glia 01/2009; 57(9):1000-13. · 4.82 Impact Factor
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ABSTRACT: The Nogo receptor (NgR), which was identified as a common receptor for three axon growth inhibitors associated with myelin, has been extensively characterized for its role in triggering growth cone collapse and arresting neurite/axon growth. Recent studies indicate that NgR is also expressed in nonneuronal cells and modulates macrophage responses during inflammation after peripheral nerve injury. In this article, we discuss the possibility that NgR might have wider effects on inflammation in a variety of neurological conditions ranging from central nervous system trauma to diseases such as multiple sclerosis or Alzheimer's disease.
Trends in Neurosciences 06/2008; 31(5):221-6. · 14.23 Impact Factor
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ABSTRACT: We report a role for Nogo receptors (NgRs) in macrophage efflux from sites of inflammation in peripheral nerve. Increasing numbers of macrophages in crushed rat sciatic nerves express NgR1 and NgR2 on the cell surface in the first week after injury. These macrophages show reduced binding to myelin and MAG in vitro, which is reversed by NgR siRNA knockdown and by inhibiting Rho-associated kinase. Fourteen days after sciatic nerve crush, regenerating nerves with newly synthesized myelin have fewer macrophages than cut/ligated nerves that lack axons and myelin. Almost all macrophages in the cut/ligated nerves lie within the Schwann cell basal lamina, while in the crushed regenerating nerves the majority migrate out. Furthermore, crush-injured nerves of NgR1- and MAG-deficient mice and Y-27632-treated rats show impaired macrophage efflux from Schwann cell basal lamina containing myelinated axons. These data have implications for the resolution of inflammation in peripheral nerve and CNS pathologies.
Neuron 04/2007; 53(5):649-62. · 14.74 Impact Factor
