A novel approach to 32-channel peripheral nervous system myelin imaging in vivo, with single axon resolution

2018 ◽  
Vol 130 (1) ◽  
pp. 163-171 ◽  
Author(s):  
Joey Grochmal ◽  
Wulin Teo ◽  
Hardeep Gambhir ◽  
Ranjan Kumar ◽  
Jo Anne Stratton ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nerve ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Tibial Nerve ◽  
Nile Red ◽  
Spectral Imaging ◽  
High Definition ◽  
Myelin Imaging

OBJECTIVEIntravital spectral imaging of the large, deeply situated nerves in the rat peripheral nervous system (PNS) has not been well described. Here, the authors have developed a highly stable platform for performing imaging of the tibial nerve in live rodents, thus allowing the capture of high-resolution, high-magnification spectral images requiring long acquisition times. By further exploiting the qualities of the topically applied myelin dye Nile red, this technique is capable of visualizing the detailed microenvironment of peripheral nerve demyelination injury and recovery, while allowing us to obtain images of exogenous Schwann cell myelination in a living animal.METHODSThe authors caused doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs to the zone of injury. Prior to acquiring images of myelin recovery in these nerves, a tibial nerve window was constructed using a silicone hemitube, a fast drying silicone polymer, and a small coverslip. This construct was then affixed to a 3D-printed nerve stage, which in turn was affixed to an external fixation/microscope stage device. Myelin visualization was facilitated by the topical application of Nile red.RESULTSThe authors reliably demonstrated intravital peripheral nerve myelin imaging with micron-level resolution and magnification, and minimal movement artifact. The detailed microenvironment of nerve remyelination can be vividly observed, while exogenously applied Schwann cells and skin-derived precursor Schwann cells can be seen myelinating axons.CONCLUSIONSTopically applied Nile red enables intravital study of myelin in the living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable intravital peripheral nerve imaging, making possible high-definition spectral imaging with long acquisition times.

scholarly journals Dependence on Schwann Cell-Derived Laminin-γ1 Differentiates Early Lymphoid and Myeloid Development

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-37
Author(s):  
Kristin Komnick ◽  
Jennifer May ◽  
Pouneh Kermani ◽  
Sreemanti Basu ◽  
Irene Hernandez ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Nervous System ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Adrenergic Nerve ◽  
Spleen Size ◽  
Mouse Line ◽  
Myeloid Development

Blood cell production is regulated by peripheral nerve fibers that innervate the bone marrow. However, little is known about the development or maintenance of hematopoietic innervation. Schwann cells (SCs) are the primary axon 'support cells' of the peripheral nervous system (PNS), and abnormal SC development is sufficient to impair peripheral nerve function. SCs are also the primary repair cell for the PNS which makes them an attractive therapeutic target for normalization of drug or malignancy-induced 'hematopoietic neuropathy'. We hypothesized that neural regulation of hematopoiesis is dependent on SC development. To test this hypothesis, we used the Myelin Protein Zero-Cre (MP0-Cre); Lamc1fl/fl mouse line in which laminin-γ1 expression is deleted from SC precursors and their progeny1. Early SC maturation is dependent on autocrine SC precursor-derived molecules such as laminin-γ1. SC differentiation arrests prior to axon sorting and ensheathment in MP0-Cre; Lamc1fl/fl mice, and causes a global peripheral neuropathy that persists throughout the lifetime of the animal. Preliminary hematopoietic analysis of 'steady state' MP0-Cre; Lamc1fl/fl and littermate control mice has shown the following: (1) MP0-Cre; Lamc1fl/fl bone marrow is innervated, and Cre-mediated gene recombination occurs in cells immunophenotypically consistent with SCs throughout the peripheral nervous system, including those in the bone marrow; (2) MP0-Cre; Lamc1fl/fl mice are lymphopenic but not neutropenic; (3) MP0-Cre; Lamc1fl/fl mice have significantly reduced spleen size and cellularity; and (4) MP0-Cre; Lamc1fl/fl bone marrow has an ~50% reduction in Lin-Sca-1+Kit+(LSK) cells (measured as a percentage of the Lin- compartment of the bone marrow). These results are consistent with earlier work by our groups in which we found that global Lamc1 gene deletion in adult mice induced peripheral blood lymphopenia, reduced spleen size, and a niche-dependent reduction of lymphoid progenitor and precursor cells that was secondary to increased lymphoid precursor cell apoptosis and reduced proliferation (UBC-CreERT2; Lamc1fl/fl mouse line). As with the SC-specific laminin-γ1 deficient mice, myelopoiesis was preserved in the UBC-CreERT2; Lamc1fl/fl mice. Based on results from MP0-Cre; Lamc1fl/fl and UBC-CreERT2; Lamc1fl/fl mice, we conclude that early lymphoid but not myeloid development requires laminin-γ1 expression by MP0-Cre-targetted niche cells, i.e. Schwann Cells. Our results are consistent with reports from other labs that hematopoietic sympathetic neuropathy promotes aberrant myeloid expansion at the expense of lymphopoiesis2. Going forward, we will determine whether lymphopoietic development is dependent on global versus laminin-specific SC-derived cues, and whether these signals are transmitted directly between SCs and lymphoid biased HSPCs or indirectly via other components of the hematopoietic niche. We anticipate that this line of investigation will provide molecular insights and pharmacologic targets for prevention and or normalization of the 'hematopoietic neuropathy' induced by diabetes, aging, neurotoxic chemotherapies and myeloid malignancies. REFERENCES: 1 Yu, W. M., Feltri, M. L., Wrabetz, L., Strickland, S. & Chen, Z. L. Schwann cell-specific ablation of laminin gamma1 causes apoptosis and prevents proliferation. J Neurosci25, 4463-4472, doi:10.1523/JNEUROSCI.5032-04.2005 (2005). 2 Maryanovich, M. et al. Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche. Nat Med24, 782-791, doi:10.1038/s41591-018-0030-x (2018). Disclosures No relevant conflicts of interest to declare.

scholarly journals GAP-43 is expressed by nonmyelin-forming Schwann cells of the peripheral nervous system.

1992 ◽  
Vol 116 (6) ◽  
pp. 1455-1464 ◽  
Author(s):  
R Curtis ◽  
H J Stewart ◽  
S M Hall ◽  
G P Wilkin ◽  
R Mirsky ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Glial Cells ◽  
Distal Stump ◽  
Metabolic Labeling ◽  
General Role

Recently it has been demonstrated that the growth-associated protein GAP-43 is not confined to neurons but is also expressed by certain central nervous system glial cells in tissue culture and in vivo. This study has extended these observations to the major class of glial cells in the peripheral nervous system, Schwann cells. Using immunohistochemical techniques, we show that GAP-43 immunoreactivity is present in Schwann cell precursors and in mature non-myelin-forming Schwann cells both in vitro and in vivo. This immunoreactivity is shown by Western blotting to be a membrane-associated protein that comigrates with purified central nervous system GAP-43. Furthermore, metabolic labeling experiments demonstrate definitively that Schwann cells in culture can synthesize GAP-43. Mature myelin-forming Schwann cells do not express GAP-43 but when Schwann cells are removed from axonal contact in vivo by nerve transection GAP-43 expression is upregulated in nearly all Schwann cells of the distal stump by 4 wk after denervation. In contrast, in cultured Schwann cells GAP-43 is not rapidly upregulated in cells that have been making myelin in vivo. Thus the regulation of GAP-43 appears to be complex and different from that of other proteins associated with nonmyelin-forming Schwann cells such as N-CAM, glial fibrillary acidic protein, A5E3, and nerve growth factor receptor, which are rapidly upregulated in myelin-forming cells after loss of axonal contact. These observations suggest that GAP-43 may play a more general role in the nervous system than previously supposed.

Peripheral Nerve

2016 ◽  
pp. 119-134
Author(s):  
Robert J. Spinner
Keyword(s):  
Nervous System ◽  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Peripheral Nervous System ◽  
Systematic Approach ◽  
Major Focus ◽  
Inflammatory Conditions ◽  
The Common ◽  
Oral Examinations

Peripheral nerve is an important and historical part of neurosurgery. It also has been a major focus of both the written and oral examinations administered by the American Board of Neurological Surgeons (ABNS). The Oral Board candidate must be prepared for potentially one to several questions on some of the common disorders of the peripheral nervous system. In this chapter, a systematic approach to peripheral nerve problems is presented. Common areas that might be examined include tumors, injuries, inflammatory conditions, entrapments, and neuropathic pain. Five cases are illustrated, and “pearls” are provided. At the conclusion of the chapter are nine photographs representing problems the Oral Board candidate should be able to identify and answer.

scholarly journals 3D in vitro peripheral nervous system organoid using mouse primary dorsal root ganglion neurons and Schwann cells

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S124
Author(s):  
Woon-Hae Kim ◽  
Hyun-Gyu Kang ◽  
Taehoon H. Kim ◽  
Yoon Jeong Mo ◽  
Yu Seon Kim ◽  
...  
Keyword(s):  
Nervous System ◽  
Dorsal Root Ganglion ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

Toward in vivo determination of peripheral nervous system immune activity in amyotrophic lateral sclerosis

2019 ◽  
Vol 59 (5) ◽  
pp. 567-576 ◽  
Author(s):  
Stefanie Schreiber ◽  
Frank Schreiber ◽  
Cornelia Garz ◽  
Grazyna Debska‐Vielhaber ◽  
Anne Assmann ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Activity ◽  
Lateral Sclerosis

Tenascin-R is expressed by Schwann cells in the peripheral nervous system

2001 ◽  
Vol 64 (1) ◽  
pp. 70-78 ◽  
Author(s):  
Rainer Probstmeier ◽  
J�rg Nellen ◽  
Sergio Gloor ◽  
Anton Wernig ◽  
Penka Pesheva
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Schwann Cells
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