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Journal article
Dependence of Regenerated Sensory Axons on Continuous Neurotrophin-3 Delivery
The Journal of neuroscience, v 32(38), pp 13206-13220
19 Sep 2012
PMID: 22993437
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Previous studies have shown that injured dorsal column sensory axons extend across a spinal cord lesion site if axons are guided by a gradient of neurotrophin-3 (NT-3) rostral to the lesion. Here we examined whether continuous NT-3 delivery is necessary to sustain regenerated axons in the injured spinal cord. Using tetracycline-regulated (tet-off) lentiviral gene delivery, NT-3 expression was tightly controlled by doxycycline administration. To examine axon growth responses to regulated NT-3 expression, adult rats underwent a C3 dorsal funiculus lesion. The lesion site was filled with bone marrow stromal cells, tet-off-NT-3 virus was injected rostral to the lesion site, and the intrinsic growth capacity of sensory neurons was activated by a conditioning lesion. When NT-3 gene expression was turned on, cholera toxin beta-subunit-labeled sensory axons regenerated into and beyond the lesion/graft site. Surprisingly, the number of regenerated axons significantly declined when NT-3 expression was turned off, whereas continued NT-3 expression sustained regenerated axons. Quantification of axon numbers beyond the lesion demonstrated a significant decline of axon growth in animals with transient NT-3 expression, only some axons that had regenerated over longer distance were sustained. Regenerated axons were located in white matter and did not form axodendritic synapses but expressed presynaptic markers when closely associated with NG2-labeled cells. A decline in axon density was also observed within cellular grafts after NT-3 expression was turned off possibly via reduction in L1 and laminin expression in Schwann cells. Thus, multiple mechanisms underlie the inability of transient NT-3 expression to fully sustain regenerated sensory axons.
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Details
- Title
- Dependence of Regenerated Sensory Axons on Continuous Neurotrophin-3 Delivery
- Creators
- Shaoping Hou - Drexel University, Neurobiology and AnatomyLaShae Nicholson - University Hospital HeidelbergErna van Niekerk - University of California San DiegoMelanie Motsch - University Hospital HeidelbergArmin Blesch - Univ Heidelberg Hosp, Spinal Cord Injury Ctr, D-69118 Heidelberg, Germany
- Publication Details
- The Journal of neuroscience, v 32(38), pp 13206-13220
- Publisher
- Soc Neuroscience
- Number of pages
- 15
- Grant note
- 161456 / Craig H. Neilsen Foundation R01NS054883 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) IRG268282 / European Community; European Commission Wings for Life NS054883 / National Institutes of Health-National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000309258100024
- Scopus ID
- 2-s2.0-84866411739
- Other Identifier
- 991020099919704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences