on bidirectional axo-glia signaling and on downstream molecular mechanisms in both, the peripheral and central nervous system. We do not capture any email address. The stick-like structure model (15, 50) of MBP is useful to explain the compaction between 2 layers of cell membranes in the myelin structural unit (Fig. S1B). (B) Anchoring particles (indicated by white arrowheads) in the myelin sheath. Although this process Studies on Shiverer (Shi/Shi) mice have shown that MBP is 1 of the proteins that is important for maintaining the normal structure of the myelin sheath. In the case of CSPGs, their removal using the enzyme chondroitinase ABC also improved regeneration [ 74 , 96 ], although it did not have a differential effect on motor versus sensory … White arrows indicated a bridge between 2 myelin sheaths (M1 and M2 or M3 and M4). Anchoring of the myelin sheath by lipophilin particles might be required for the formation of a compacted myelin sheath. NGFR P75 is a marker of both MSCs and NMSCs. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA, e In all cases the Ref. Flashcards. S3). What triggers Schwann cell transdifferentiation in Match. Neuroregeneration refers to the regrowth or repair of nervous tissues, cells or cell products. Immunofluorescence staining showed that the distribution of MSCs in the sciatic nerve was significantly lower than in the optic nerve and oculomotor nerve. It is important to recognise that axonal injury has implications for the entire length of the neuron, as well as immediate functional consequences for the brain. The regeneration of mammalian peripheral nerves after injury requires glial cells called Schwann cells (SCs), which dedifferentiate to a progenitor-like state to direct the regeneration process. There are 4 main types of mature Schwann cells. Published by PNAS. Furthermore, the expression of MBP in the nerve tube group was lower than that in the autologous nerve graft (Fig. steps of nerve regeneration. These observations indicated that it might be not possible to distinguish between afferent and efferent nerve fibers based solely on the axon diameter. Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA, c Immunofluorescence staining for NF200, an axonal marker, showed that the axons have different diameters within each nerve (SI Appendix, Fig. The current gold standard treatment for critical-sized nerve defects is autologous nerve graft transplantation; however, this method is limited in many ways and does not always lead to satisfactory outcomes. During the experimental repair of peripheral nerve injury (26⇓–28), the sciatic nerve is usually used as the target (29⇓⇓–32). Those particles are radially distributed and pass through multiple double-bilayers (55). do not need to formally request permission to reproduce material contained in this Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA The regeneration here begins a few weeks after the injury has had time to rest. Lipophilin accounts for about 50% of the PLP (15). Lipophilin is a distinct component of the PLP fraction, and is not equivalent to PLP (15, 56). 2B) were observed on the myelin sheaths of all 3 types of nerves. 4A), indicating that they were also formed by the same Schwann cell, but they have no axons inside. 1). demyelinating and axonal diseases of the PNS? peripheral neuropathies and to develop therapeutic strategies that promote nerve integrity and function. Peripheral nerve injury is a common disease that affects more than 20 million people in the United States alone and remains a major burden to society. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. The relative expression levels of GFAP on day 7 and day 14 were ranked as follows: Nerve tube transplantation < autologous nerve transplantation < end-to-end anastomosis. Structural unit of the myelin sheath (double- bilayer) and particles. 2 A and C). It has become apparent that a purely microsurgical approach to nerve repair will fail to address the complex cellular and molecular events of peripheral nerve regeneration. DAPI, MBP101, GFAP NGFR P75, and NF200 immunofluorescent staining of the cross-sections of growth cones in the nerve tube obtained on the 30th day after transplantation. is available on our Permission Requests page. The myelin sheath (wrapped around the C-fiber in the Remark bundle) formed by NMSCs is composed of a single layer of double-bilayers. In green, myelinated internodes are visualized (antibody against myelin basic protein), together with axons in red (antibody against Reproduced material should be attributed as follows: If the material has been adapted instead of reproduced from the original RSC publication There are 4 main isoforms of MBCs (45, 48), with molecular mass of 21.5, 18.5, 17, and 14 kDa, respectively, and its amino acid sequence is highly conserved throughout different species (43). 4A). These findings indicate that all of 3 types contain both MSCs and NMSCs. The adult mammalian peripheral nervous system (PNS) harbors an exceptional In these mice, the myelin sheath of the central nervous system is characterized by a lack of MDL (40). Nerve regeneration proceeds from the peripheral recipient cornea into the donor cornea very slowly and, even many years later, the innervation density of the grafted tissue remains far less than that of the host, peripheral cornea (Figure 7). Since Schwann cells are wrapped around axons, differences in the axon distribution would naturally lead to differences in the Schwann cell distribution. In contrast, in the cross-sections of the sciatic nerve (Fig. In order to answer these questions, we take advantage of different animal models for peripheral nerve injuries combined with in-vitro systems of myelinating glia-neuron co-cultures. For our research, we are taking advantage of mouse models for autoimmune encephalomyelitis, leukodystrophies and toxin-induced A large genomic dataset reveals ancient demographic events that accompanied the transition to agriculture and changes in metallurgic practices in France. 1). As shown in SI Appendix, Fig. 2C), the nonlayered myelin sheath (between 2 black arrowheads in Fig. Of note, the myelin structure was grossly normal in the spinal nerve roots and sciatic nerves of the Shiverer mice at ∼35 d of age (42). S1A, there was a difference in the distribution of Schwann cells in different nerves. Peripheral nerves have Schwann cells and endoneurium that helps in regeneration. demyelination in the central nervous system. TEM images of cross-sections of the optic nerve, oculomotor nerve, and sciatic nerve. Observing the structure and regeneration of the myelin sheath in peripheral nerves following injury and during repair would help in understanding the pathogenesis and treatment of neurological diseases caused by an abnormal myelin sheath. The relative expression levels of NGFR P75 did not show obvious trends either based on the group or the time point. Neuregulin-1 expressed by neurons controls almost all steps of Schwann cell development in This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1910292116/-/DCSupplemental. When an axon is damaged, the distal segment undergoes Wallerian degeneration, losing its myelinsheath. As shown in Fig. However, the MDL in the nerve tube group were abnormal (Fig. These suggested that compacted myelin could not be formed without particles. However, after acute nerve injury, Neuregulin-1 expression switches from neurons to glia, where it contributes to nerve repair and remyelination. To observe the structure and regeneration of the myelin sheath during rat (SI Appendix, Section S1) peripheral nerve injury repair, transmission electron microscopy (TEM) observation (SI Appendix, Section S2), immunofluorescence staining (SI Appendix, Section S3), and transcriptome analyses (SI Appendix, Sections S4 and S5) of the myelin sheath were performed following end-to-end anastomosis, autologous nerve transplantation, and nerve tube (SI Appendix, Section S6) transplantation in a rat model of sciatic nerve injury (SI Appendix, Section S7), with the optic nerve, oculomotor nerve, sciatic nerve (SI Appendix, Section S8), and Schwann cells (SI Appendix, Section S9) used as controls. There is a large body of existing literature about the structure and formation of the myelin sheath (11⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓–22), but there is confusion regarding some issues, such as the development and roles of major dense lines (MDL), myelin basic protein (MBP), myelin compaction, and anchoring.

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