GDNF selectively promotes regeneration of injury-primed sensory neurons in the lesioned spinal cord

Charles D Mills, Andrew J Allchorne, Robert G. Griffin, Clifford J Woolf, Michael Costigan

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Axonal regeneration within the CNS fails due to the growth inhibitory environment and the limited intrinsic growth capacity of injured neurons. Injury to DRG peripheral axons induces expression of growth associated genes including members of the glial-derived neurotrophic factor (GDNF) signaling pathway and "preconditions" the injured cells into an active growth state, enhancing growth of their centrally projecting axons. Here, we show that preconditioning DRG neurons prior to culturing increased neurite outgrowth, which was further enhanced by GDNF in a bell-shaped growth response curve. In vivo, GDNF delivered directly to DRG cell bodies facilitated the preconditioning effect, further enhancing axonal regeneration beyond spinal cord lesions. Consistent with the in vitro results, the in vivo effect was seen only at low GDNF concentrations. We conclude that peripheral nerve injury upregulates GDNF signaling pathway components and that exogenous GDNF treatment selectively promotes axonal growth of injury-primed sensory neurons in a concentration-dependent fashion.
Original languageEnglish
Pages (from-to)185-94
Number of pages10
JournalMolecular and Cellular Neuroscience
Volume36
Issue number2
DOIs
Publication statusPublished - Oct 2007

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