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Metallothionein promotes regenerative axonal sprouting of dorsal root ganglion neurons after physical axotomy


Leung, JYK and Bennett, WR and Herbert, RP and West, AK and Lee, PR and Wake, H and Fields, RD and Chuah, MI and Chung, RS, Metallothionein promotes regenerative axonal sprouting of dorsal root ganglion neurons after physical axotomy, Cellular and Molecular Life Sciences, 69, (5) pp. 809-817. ISSN 1420-9071 (2012) [Refereed Article]

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Copyright 2011 Springer Basel AG

DOI: doi:10.1007/s00018-011-0790-7


Prior studies have reported that metallothionein I/II (MT) promote regenerative axonal sprouting and neurite elongation of a variety of central nervous system neurons after injury. In this study, we evaluated whether MT is capable of modulating regenerative axon outgrowth of neurons from the peripheral nervous system. The effect of MT was firstly investigated in dorsal root ganglion (DRG) explants, where axons were scratch-injured in the presence or absence of exogenous MT. The application of MT led to a significant increase in regenerative sprouting of neurons 16 h after injury. We show that the pro-regenerative effect of MT involves an interaction with the lowdensity lipoprotein receptor megalin, which could be blocked using the competitive antagonist RAP. Pre-treatment with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 also completely abrogated the effect of exogenous MT in promoting axonal outgrowth. Interestingly, we only observed megalin expression in neuronal soma and not axons in the DRG explants. To investigate this matter, an in vitro injury model was established using Campenot chambers, which allowed the application of MT selectively into either the axonal or cell body compartments after scratch injury was performed to axons. At 16 h after injury, regenerating axons were significantly longer only when exogenous MT was applied solely to the soma compartment, in accordance with the localized expression of megalin in neuronal cell bodies. This study provides a clear indication that MT promotes axonal regeneration of DRG neurons, via a megalin- and MAPK-dependent mechanism.

Item Details

Item Type:Refereed Article
Keywords:Metallothionein; Neuronal injury; Neurite sprouting; Megalin; Dorsal root ganglion neurons
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Leung, JYK (Dr Jacqueline Leung)
UTAS Author:Bennett, WR (Dr Bill Bennett)
UTAS Author:Herbert, RP (Ms Rosalind Herbert)
UTAS Author:West, AK (Professor Adrian West)
UTAS Author:Chuah, MI (Associate Professor Inn Chuah)
UTAS Author:Chung, RS (Associate Professor Roger Chung)
ID Code:74536
Year Published:2012 (online first 2011)
Web of Science® Times Cited:12
Deposited By:Menzies Institute for Medical Research
Deposited On:2011-12-07
Last Modified:2013-11-15

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