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Published on: November 21, 2012
Cell adhesion molecule L1 modulates nerve-growth-factor-induced CGRP-IR fiber sprouting
Nagarathnamma Chaudhry1, Udesh de Silva, George M Smith
1Department of Physiology, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0298, USA.
Experimental Neurology
|July 25, 2006
Summary
Nerve growth factor (NGF) promotes nerve fiber regeneration after spinal cord injury. However, co-expressing cell adhesion molecule L1 with NGF significantly reduces this sprouting, a finding specific to L1.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Spinal Cord Injury Research
Background:
- Spinal cord injury (SCI) impairs nerve regeneration.
- Nerve growth factor (NGF) promotes axonal sprouting.
- Cell adhesion molecules (CAMs) role in neural repair is under investigation.
Purpose of the Study:
- To investigate the effect of co-expressing NGF and CAMs on CGRP-IR fiber sprouting after SCI.
- To explore the underlying mechanisms of L1-mediated reduction in NGF-induced sprouting.
Main Methods:
- Adenovirus-mediated overexpression of NGF and CAMs (L1, NCAM, N-cadherin) in vivo.
- Assessment of calcitonin-gene-related peptide immunoreactive (CGRP-IR) fiber sprouting.
- In vitro studies using astrocytes and dorsal root ganglion (DRG) neurons to assess neurite outgrowth.
- Investigating the role of semaphorin 3A (Sema3A) signaling.
Main Results:
- NGF overexpression significantly increased CGRP-IR fiber sprouting.
- Co-expression of L1 with NGF significantly reduced sprouting compared to NGF alone.
- NCAM and N-cadherin co-expression did not affect NGF-induced sprouting.
- In vitro, L1 did not inhibit NGF-induced neurite outgrowth on astrocytes, but Sema3A co-expression reduced DRG neuron outgrowth on L1-expressing astrocytes.
Conclusions:
- Reduced sprouting is specific to L1 co-expression with NGF.
- L1 may potentiate semaphorin 3A signaling, inhibiting CGRP-IR axon sprouting after SCI.
- Further research into L1-Sema3A interactions is warranted for therapeutic strategies in SCI.
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