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Directing dopaminergic fiber growth along a preformed molecular pathway from embryonic ventral mesencephalon transplants in the rat brain
Journal article   Open access   Peer reviewed

Directing dopaminergic fiber growth along a preformed molecular pathway from embryonic ventral mesencephalon transplants in the rat brain

Y Jin, C Zhang, K S Ziemba, G A Goldstein, P G Sullivan and G M Smith
Journal of neuroscience research, v 89(5), pp 619-627
May 2011
DOI: https://doi.org/10.1002/jnr.22575
PMID: 21337366
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1002/jnr.22575View
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Abstract

Parkinson Disease - therapy Growth Cones - physiology Parkinson Disease - pathology Brain Tissue Transplantation - pathology Mesencephalon - cytology Neural Pathways - growth & development Cells, Cultured Rats Growth Cones - pathology Neural Pathways - physiology Rats, Sprague-Dawley Animals Mesencephalon - embryology Growth Cones - ultrastructure Dopamine - physiology Mesencephalon - transplantation Cell Line, Tumor Neural Pathways - metabolism Female Parkinson Disease - metabolism Brain Tissue Transplantation - methods
To identify guidance molecules to promote long-distance growth of dopaminergic axons from transplanted embryonic ventral mesencephalon (VM) tissue, three pathways were created by expressing green fluorescent protein (GFP), glial cell line-derived neurotrophic factor (GDNF), or a combination of GDNF/GDNF receptor α1 (GFRα1) along the corpus callosum. To generate the guidance pathway, adenovirus encoding these transcripts was injected at four positions along the corpus callosum. In all groups, GDNF adenovirus was also injected on the right side 2.5 mm from the midline at the desired transplant site. Four days later, a piece of VM tissue from embryonic day 14 rats was injected at the transplant site. All rats also received daily subcutaneous injections of N-acetyl-L-cysteinamide (NACA; 100 μg per rat) as well as chondroitinase ABC at transplant site (10 U/ml, 2 μl). Two weeks after transplantation, the rats were perfused and the brains dissected out. Coronal sections were cut and immunostained with antibody to tyrosine hydroxylase (TH) to identify and count dopaminergic fibers in the corpus callosum. In GFP-expressing pathways, TH(+) fibers grew out of the transplants for a short distance in the corpus callosum. Very few TH(+) fibers grew across the midline. However, pathways expressing GDNF supported more TH(+) fiber growth across the midline into the contralateral hemisphere. Significantly greater numbers of TH(+) fibers grew across the midline in animals expressing a combination of GDNF and GFRα1 in the corpus callosum. These data suggest that expression of GDNF or a combination of GDNF and GFRα1 can support the long-distance dopaminergic fiber growth from a VM transplant, with the combination having a superior effect.

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