Deciphering peripheral nerve myelination by using Schwann cell expression profiling

Washington University in St. Louis, San Luis, Missouri, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 07/2002; 99(13):8998-9003. DOI: 10.1073/pnas.132080999
Source: PubMed


Although mutations in multiple genes are associated with inherited demyelinating neuropathies, the molecular components and pathways crucial for myelination remain largely unknown. To approach this question, we performed genome-wide expression analysis in several paradigms where the status of peripheral nerve myelination is dynamically changing. Anchor gene correlation analysis, a form of microarray analysis that integrates functional information, using correlation-based clustering, with a statistically rigorous test, the Westfall and Young step-down algorithm, was applied to this data set. Biological pathways active in myelination, genes encoding proteins involved in myelin synthesis, and genes whose mutation results in myelination defects were identified. Many known genes and previously uncharacterized ESTs not heretofore associated with myelination were also identified. One of these ESTs, MASR (myelin-associated SUR4 protein), encodes a member of the SUR4 family of fatty acid desaturases, enzymes involved in elongation of very long chain fatty acids. Its specific localization in myelinating Schwann cells indicates a crucial role for MASR in normal myelin lipid synthesis.

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Available from: Toshiyuki Araki, Jul 10, 2014
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    • " The quantification of the normalized density of cleaved caspase - 3 ( A ) and cleaved caspase - 9 ( B ) is shown . Values are means ± SEM of six independent experiments . * p < 0 . 05 . development and the remyelination process after nerve injury have revealed that cholesterol / lipid metabolism in peripheral nerve myelination is also important ( Nagarajan et al . , 2002 ; Verheijen et al . , 2003 ) . Next , we examined the activation of Acly , which is a marker of lipid - synthesis enzymes . Together with the expression of MBP , MeCbl promoted the expression of Acly in SCs in the differentiation medium but not in the growth medium ( Figure 4D ) . In addition , to clarify the increasing expression of MB"
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    ABSTRACT: Schwann cells (SCs) are constituents of the peripheral nervous system. The differentiation of SCs in injured peripheral nerves is critical for regeneration after injury. Methylcobalamin (MeCbl) is a vitamin B12 analog that is necessary for the maintenance of the peripheral nervous system. In this study, we estimated the effect of MeCbl on SCs. We showed that MeCbl downregulated the activity of Erk1/2 and promoted the expression of the myelin basic protein in SCs. In a dorsal root ganglion neuron-SC coculture system, myelination was promoted by MeCbl. In a focal demyelination rat model, MeCbl promoted remyelination and motor and sensory functional regeneration. MeCbl promoted the in vitro differentiation of SCs and in vivo myelination in a rat demyelination model and may be a novel therapy for several types of nervous disorders.
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    • "Based on its prominent reduction in the aforementioned PLP mutant mouse model with axonal degeneration, the cytosolic sirtuin member SIRT2 in OLGs may play an axon-supportive role (Werner et al., 2007). Moreover, arguing for a metabolic role of SIRT2 in SCs, this sirtuin was identified in gene expression profiling experiments as highly abundant protein in nascent SCs (Nagarajan et al., 2002). Surprisingly, SC-restricted SIRT2 knockout mice do not show axon degeneration even if aged, despite metabolic dysregulation in SCs (Beirowski et al., 2011). "
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    ABSTRACT: Long axons and their enwrapping glia (EG; Schwann cells (SCs) and oligodendrocytes (OLGs)) form a unique compound structure that serves as conduit for transport of electric and chemical information in the nervous system. The peculiar cytoarchitecture over an enormous length as well as its substantial energetic requirements make this conduit particularly susceptible to detrimental alterations. Degeneration of long axons independent of neuronal cell bodies is observed comparatively early in a range of neurodegenerative conditions as a consequence of abnormalities in SCs and OLGs . This leads to the most relevant disease symptoms and highlights the critical role that these glia have for axon integrity, but the underlying mechanisms remain elusive. The quest to understand why and how axons degenerate is now a crucial frontier in disease-oriented research. This challenge is most likely to lead to significant progress if the inextricable link between axons and their flanking glia in pathological situations is recognized. In this review I compile recent advances in our understanding of the molecular programs governing axon degeneration, and mechanisms of EG's non-cell autonomous impact on axon-integrity. A particular focus is placed on emerging evidence suggesting that EG nurture long axons by virtue of their intimate association, release of trophic substances, and neurometabolic coupling. The correction of defects in these functions has the potential to stabilize axons in a variety of neuronal diseases in the peripheral nervous system and central nervous system (PNS and CNS).
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    • "Intriguingly , leprosy bacteria appear to hijack this process and generate dedifferentiated Schwann cells by causing initial demyelination to establish the infection, colonize the cells, and subsequently reprogram them to a pSLC-like stage to spread the infection (Masaki et al., 2013; Rambukkana 2010; Rambukkana et al., 2002; Tapinos et al., 2006). In peripheral nerve injury, immune-related genes are also activated in dedifferentiated adult Schwann cells, which serve as repair cells for regeneration process (Nagarajan et al., 2002; Napoli et al., 2012). These include immune factors that activate and attract macrophages and other immune cells. "
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