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Neural Progenitor Cells Promote Axonal Growth and Alter Axonal mRNA Localization in Adult Neurons
Journal article   Open access

Neural Progenitor Cells Promote Axonal Growth and Alter Axonal mRNA Localization in Adult Neurons

Tanuja T Merianda, Ying Jin, Ashley L Kalinski, Pabitra K Sahoo, Itzhak Fischer and Jeffery L Twiss
eNeuro, v 4(1), pENEURO.0171-16.2017
Jan 2017
PMID: 28197547
url
https://doi.org/10.1523/ENEURO.0171-16.2017View
Published, Version of Record (VoR) Open

Abstract

Hepcidins - metabolism Neuronal Outgrowth - physiology Spinal Cord - metabolism GAP-43 Protein - metabolism Coculture Techniques Actins - metabolism Cells, Cultured Axons - metabolism Gene Expression Regulation - physiology Male Ganglia, Spinal - cytology Neural Stem Cells - cytology RNA, Messenger - metabolism Rats, Sprague-Dawley Culture Media, Conditioned Neuroglia - cytology Animals Actins - administration & dosage Female Neuroglia - metabolism Spinal Cord - cytology Neural Stem Cells - metabolism GAP-43 Protein - administration & dosage Ganglia, Spinal - metabolism
The inhibitory environment of the spinal cord and the intrinsic properties of neurons prevent regeneration of axons following CNS injury. However, both ascending and descending axons of the injured spinal cord have been shown to regenerate into grafts of embryonic neural progenitor cells (NPCs). Previous studies have shown that grafts composed of glial-restricted progenitors (GRPs) and neural-restricted progenitors (NRPs) can provide a permissive microenvironment for axon growth. We have used cocultures of adult rat dorsal root ganglion (DRG) neurons together with NPCs, which have shown significant enhancement of axon growth by embryonic rat GRP and GRPs/NRPs, both in coculture conditions and when DRGs are exposed to conditioned medium from the NPC cultures. This growth-promoting effect of NPC-conditioned medium was also seen in injury-conditioned neurons. DRGs cocultured with GRPs/NRPs showed altered expression of regeneration-associated genes at transcriptional and post-transcriptional levels. We found that levels of GAP-43 mRNA increased in DRG cell bodies and axons. However, hepcidin antimicrobial peptide (HAMP) mRNA decreased in the cell bodies of DRGs cocultured with GRPs/NRPs, which is distinct from the increase in cell body HAMP mRNA levels seen in DRGs after injury conditioning. Endogenous GAP-43 and β-actin mRNAs as well as reporter RNAs carrying axonally localizing 3'UTRs of these transcripts showed significantly increased levels in distal axons in the DRGs cocultured with GRPs/NRPs. These results indicate that axon growth promoted by NPCs is associated not only with enhanced transcription of growth-associated genes but also can increase localization of some mRNAs into growing axons.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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