Identification of reciprocally regulated gene modules in regenerating dorsal root ganglion neurons and activated peripheral or central nervous system glia

2003 ◽  
Vol 88 (5) ◽  
pp. 970-985 ◽  
Author(s):  
Adrian A. Cameron ◽  
Gordon Vansant ◽  
Wen Wu ◽  
Dennis J. Carlo ◽  
Charles R. ILL

1994 ◽  
Vol 107 (12) ◽  
pp. 3393-3402 ◽  
Author(s):  
G.A. Clarke ◽  
D.J. Moss

Glycoproteins that inhibit neurite outgrowth may guide growth cones during development by acting as a barrier and closing off inappropriate routes. Their continued expression in the adult central nervous system may be a key factor in preventing regeneration of central nervous system neurons. A glycoprotein of 55 kDa has been isolated from the detergent-insoluble membrane skeleton from adult chicken brain. Initial experiments showed that dorsal root ganglion neurons would not adhere to or extend neurites on a substratum coated with GP55. Furthermore, GP55 will act as a barrier to the advance of established growth cones in the presence of poly-L-lysine, laminin or G4. Central nervous system neurons from forebrain as well as dorsal root ganglion neurons from the peripheral nervous system are inhibited by GP55. GP55 is also effective in blocking the initial adhesion of neurons to a substratum of poly-L-lysine and, particularly, laminin. In contrast to the inhibition of neurite outgrowth, neuronal adhesion is concentration independent over the range tested. A preliminary investigation of the mechanism by which GP55 inhibits outgrowth suggests that a pertussis toxin-sensitive G protein is required. Preliminary evidence suggests that GP55 is anchored in the membrane by a glycosyl phosphatidylinositol moiety. GP55 is distinct from previously identified inhibitory proteins, based on the source and molecular mass, and is thus a new member of this rapidly expanding family.



IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S124
Author(s):  
Woon-Hae Kim ◽  
Hyun-Gyu Kang ◽  
Taehoon H. Kim ◽  
Yoon Jeong Mo ◽  
Yu Seon Kim ◽  
...  


1988 ◽  
Vol 107 (1) ◽  
pp. 341-351 ◽  
Author(s):  
B Seilheimer ◽  
M Schachner

The involvement of the adhesion molecules L1, N-CAM, and J1 in adhesion and neurite outgrowth in the peripheral nervous system was investigated. We prepared Schwann cells and fibroblasts (from sciatic nerves) and neurons (from dorsal root ganglia) from 1-d mice. These cells were allowed to interact with each other in a short-term adhesion assay. We also measured outgrowth of dorsal root ganglion neurons on Schwann cell and fibroblast monolayers. Schwann cells (which express L1, N-CAM, and J1) adhered most strongly to dorsal root ganglion neurons by an L1-dependent mechanism and less by N-CAM and J1. Schwann cell-Schwann cell adhesion was mediated by L1 and N-CAM, but not J1. Adhesion of fibroblasts (which express N-CAM, but not L1 or J1) to neurons or Schwann cells was mediated by L1 and N-CAM and not J1. However, inhibition by L1 and N-CAM antibodies was found to be less pronounced with fibroblasts than with Schwann cells. N-CAM was also strongly involved in fibroblast-fibroblast adhesion. Neurite outgrowth was most extensive on Schwann cells and less on fibroblasts. A difference in extent of neurite elongation was seen between small- (10-20 microns) and large- (20-35 microns) diameter neurons, with the larger neurons tending to exhibit longer neurites. Fab fragments of polyclonal L1, N-CAM, and J1 antibodies exerted slightly different inhibitory effects on neurite outgrowth, depending on whether the neurites were derived from small or large neurons. L1 antibodies interfered most strikingly with neurite outgrowth on Schwann cells (inhibition of 88% for small and 76% for large neurons), while no inhibition was detectable on fibroblasts. Similarly, although to a smaller extent than L1, N-CAM appeared to be involved in neurite outgrowth on Schwann cells and not on fibroblasts. Antibodies to J1 only showed a very small effect on neurite outgrowth of large neurons on Schwann cells. These observations show for the first time that identified adhesion molecules are potent mediators of glia-dependent neurite formation and attribute to L1 a predominant role in neurite outgrowth on Schwann cells which may be instrumental in regeneration.





Brain ◽  
2019 ◽  
Vol 142 (5) ◽  
pp. 1215-1226 ◽  
Author(s):  
Robert Y North ◽  
Yan Li ◽  
Pradipta Ray ◽  
Laurence D Rhines ◽  
Claudio Esteves Tatsui ◽  
...  

Abstract Neuropathic pain encompasses a diverse array of clinical entities affecting 7–10% of the population, which is challenging to adequately treat. Several promising therapeutics derived from molecular discoveries in animal models of neuropathic pain have failed to translate following unsuccessful clinical trials suggesting the possibility of important cellular-level and molecular differences between animals and humans. Establishing the extent of potential differences between laboratory animals and humans, through direct study of human tissues and/or cells, is likely important in facilitating translation of preclinical discoveries to meaningful treatments. Patch-clamp electrophysiology and RNA-sequencing was performed on dorsal root ganglia taken from patients with variable presence of radicular/neuropathic pain. Findings establish that spontaneous action potential generation in dorsal root ganglion neurons is associated with radicular/neuropathic pain and radiographic nerve root compression. Transcriptome analysis suggests presence of sex-specific differences and reveals gene modules and signalling pathways in immune response and neuronal plasticity related to radicular/neuropathic pain that may suggest therapeutic avenues and that has the potential to predict neuropathic pain in future cohorts.



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