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Long distance directional growth of dopaminergic axons along pathways of netrin-1 and GDNF
Journal article   Open access   Peer reviewed

Long distance directional growth of dopaminergic axons along pathways of netrin-1 and GDNF

C. Zhang, Y. Jin, K.S. Ziemba, A.M. Fletcher, B. Ghosh, E. Truit, D.M. Yurek and G.M. Smith
Experimental neurology, v 250, pp 156-164
Dec 2013
DOI: https://doi.org/10.1016/j.expneurol.2013.09.022
PMID: 24099728
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc4038353View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Axonal guidance GDNF Lentivirus Netrin-1 Parkinson's disease Tyrosine hydroxylase Ventral mesencephalon (VM) transplantation
Different experimental and clinical strategies have been used to promote survival of transplanted embryonic ventral mesencephalic (VM) neurons. However, few studies have focused on the long-distance growth of dopaminergic axons from VM transplants. The aim of this study is to identify some of the growth and guidance factors that support directed long-distance growth of dopaminergic axons from VM transplants. Lentivirus encoding either glial cell line-derived neurotrophic factor (GDNF) or netrin-1, or a combination of lenti-GDNF with either lenti-GDNF family receptor α1 (GFRα-1) or lenti-netrin-1 was injected to form a gradient along the corpus callosum. Two weeks later, a piece of embryonic day 14 VM tissue was transplanted into the corpus callosum adjacent to the low end of the gradient. Results showed that tyrosine hydroxylase (TH+) axons grew a very short distance from the VM transplants in control groups, with few axons reaching the midline. In GDNF or netrin-1 expressing groups, more TH+ axons grew out of transplants and reached the midline. Pathways co-expressing GDNF with either GFRα-1 or netrin-1 showed significantly increased axonal outgrowth. Interestingly, only the GDNF/netrin-1 combination resulted in the majority of axons reaching the distal target (80%), whereas along the GDNF/GFRα-1 pathway only 20% of the axons leaving the transplant reached the distal target. This technique of long-distance axon guidance may prove to be a useful strategy in reconstructing damaged neuronal circuits, such as the nigrostriatal pathway in Parkinson's disease. •Little is known of what factors mediate the growth of dopaminergic axons in the adult brain.•We examined factors that induced unidirectional growth of transplanted dopamine neurons.•GDNF, GFR-α1, and netrin-1 supported some long distance growth in the adult brain.•Combinations of GDNF/GFR-α1 or GDNF/netrin-1 supported robust growth over long distances.•Such factors could be used to reconstruct the nigrostriatal pathway in Parkinson's models.

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16 citations in Web of Science
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Domestic collaboration
Web of Science research areas
Neurosciences
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