Adult central nervous system (CNS) axons fail to regenerate after injury, and one of the hurdles limiting CNS regeneration is the presence of potent inhibitory molecules in adult white matter. However, multipotent neural progenitor cells exhibit remarkably extensive axonal elongation through adult white matter when grafted in vivo (Lu et al., 2012), suggesting either that early stage neurons are not inhibited by, or are actually stimulated by, white matter. To address these possibilities, we used multipotent neural progenitor cells (NPCs) isolated from E12 mouse spinal cords for cell culture on adult CNS myelin in vitro and compared findings to cells cultured on non-myelin substrates.
Compared to cells cultured in the absence of myelin, adult DRG neurons exhibited a reduction in neurite outgrowth on myelin, whereas NPC cultures exhibited a significant increase in neurite length. While adult neurite growth inhibition is mediated in part by interactions with Nogo receptors and their ligands, Nogo, MAG, and OMgp, we found no change in neurite outgrowth when neural progenitor cells were plated on Nogo, MAG, or OMgp-deficient myelin compared to wild-type myelin. This suggests that classic adult myelin-related inhibitory mechanisms are not involved in facilitation of developing neuronal process outgrowth, and that other mechanisms are likely to be involved. Overall, these findings indicate that one of the mechanisms underlying the remarkable growth ability of early stage neurons in the injured adult CNS is a stimulatory influence of adult myelin.
|Advisor:||Tuszynski, Mark H.|
|Commitee:||Tour, Elvira, Wasserman, Steven|
|School:||University of California, San Diego|
|School Location:||United States -- California|
|Source:||MAI 53/02M(E), Masters Abstracts International|
|Keywords:||Extracellular signal-regulated protein kinase, Myelin, Neural, Regeneration, Stem cell|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be