Document Detail

Redirection of doublecortin-positive cell migration by over-expression of the chemokines MCP-1, MIP-1α and GROα in the adult rat brain.
MedLine Citation:
PMID:  24361178     Owner:  NLM     Status:  Publisher    
Inflammation-induced chemoattraction plays a major role in adult subventricular zone (SVZ)- derived precursor cell migration following neural cell loss, in particular through the release of chemokines by activated microglia and macrophages. We previously demonstrated that MCP-1 (CCL2), MIP-1α (CCL3) and GRO-α (CXCL1) are up-regulated following neural cell loss in the adult striatum and act as potent chemoattractants for SVZ-derived precursor cells in vitro. Based on these observations, the current study aimed to examine the individual effect of MCP-1, MIP-1α and GRO-α on the migration of adult SVZ-derived neural precursor cells in vivo. To address this without the confounding effects of injury- induced chemotactic cues, adeno-associated viral (AAV)2-mediated in vivo gene transfer was used to ectopically express either MCP-1, MIP-1α or GRO-α, or the control protein RFP in the normal adult rat striatum. The extent of doublecortin (Dcx) -positive cell recruitment from the SVZ into the striatal parenchyma was then determined at 4 and 8 weeks following AAV2 injection. Ectopic expression either of MCP-1 or MIP-1α in the normal adult rat brain significantly increased the number of Dcx-positive cells and the extent of their migration into the striatum at both 4 and 8 weeks after vector injection but did not promote either precursor cell proliferation or neural differentiation. In contrast, while over-expression of GRO-α 4 weeks after vector injection induced a significant increase in Dcx-positive cell migration compared to control, this effect was reduced to control levels by 8 weeks post injection. Further, direct comparison between MCP-1, MIP-1α and GRO-α at both 4 and 8 weeks post vector injection indicated that GROα may have a reduced effect in inducing Dcx-positive cell migration when compared to MCP-1. Combined, these results confirm that over-expression of the chemokines MCP-1, MIP-1α and GRO-α can override cues directing precursor cell migration along the RMS and provides a mechanism by which neural precursor cell migration can be redirected into a non-neurogenic region. Differences in the migratory effect observed between individual chemokine may be due to ligand-binding affinity and/or receptor expression on SVZ-derived precursor cells.
Siu Kwan Tang; Rosemary Ann Knobloch; Christof Maucksch; Bronwen Connor
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-17
Journal Detail:
Title:  Neuroscience     Volume:  -     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier Ltd.
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