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Targeting axon growth from neuronal transplants along preformed guidance pathways in the adult CNS
Journal article   Open access   Peer reviewed

Targeting axon growth from neuronal transplants along preformed guidance pathways in the adult CNS

Kristine S Ziemba, Nagarathnamma Chaudhry, Alexander G Rabchevsky, Ying Jin and George M Smith
The Journal of neuroscience, v 28(2), pp 340-348
09 Jan 2008
PMID: 18184776
url
https://doi.org/10.1523/JNEUROSCI.3819-07.2008View
Published, Version of Record (VoR) Open

Abstract

Animals, Newborn Green Fluorescent Proteins - metabolism Corpus Callosum - metabolism Nerve Growth Factor - metabolism Corpus Callosum - surgery Rats Adenoviridae - physiology Neurons - cytology Axons - physiology Ganglia, Spinal - cytology Semaphorins - metabolism Neural Pathways - physiology Rats, Sprague-Dawley Pregnancy Animals Neurons - physiology Fibroblast Growth Factor 2 - metabolism Female Calcitonin Gene-Related Peptide - metabolism Cell Transplantation - physiology Cell Survival - physiology Cell Movement
To re-establish neuronal circuits lost after CNS injury, transplanted neurons must be able to extend axons toward their appropriate targets. Such growth is highly restricted within the adult CNS attributable to the expression of inhibitory molecules and general lack of guidance cues to direct axon growth. This environment typically induces random patterns of growth and aberrant innervation, if growth occurs at all. To target the growth of axons from neuronal transplants, we are using viral vectors to create guidance pathways before neuronal transplantation. In this study, we transplanted postnatal rat dorsal root ganglia neurons into the corpus callosum of adult rats. Replication-incompetent adenoviruses encoding growth or guidance factors were injected along the desired pathway 1 week before cell transplantation, allowing time for sufficient protein expression by host glial cells. With expression of nerve growth factor (NGF) and basic fibroblast growth factor, sensory axons were able to grow along the corpus callosum, across the midline, and toward an NGF-expressing target in either the contralateral striatum or cortex: a distance of 7-8 mm including a 90 degree turn from white matter into gray matter. Furthermore, expression of semaphorin 3A slightly dorsal and lateral to the turning point increased the number of axons turning into the striatal target. These results show that judicious expression of neuron-specific chemoattractant and chemorepellant molecules using viral vectors can support and target axon growth from neuronal transplants in the adult CNS.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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