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Metallothionein-III Inhibits Initial Neurite Formation in Developing Neurons as Well as Postinjury, Regenerative Neurite Sprouting


Chung, RS and Vickers, JC and Chuah, MI and Eckhardt, BL and West, AK, Metallothionein-III Inhibits Initial Neurite Formation in Developing Neurons as Well as Postinjury, Regenerative Neurite Sprouting, Experimental Neurology, 178 pp. 1-12. ISSN 0014-4886 (2002) [Refereed Article]

DOI: doi:10.1006/exnr.2002.8017


Human metallothionein-III (MT-III) is an inhibitory factor deficient in the Alzheimer's disease (AD) brain. MT-III has been identified as an inhibitor of neurite sprouting, and its deficiency has been proposed to be involved in the formation of neurofibrillary tangles (NFT) in the neuropathology of AD. However, there has been limited investigation of the proposed neurite growth inhibitory properties of MT-III. We have applied recombinant human MT-III to both single cell embryonic cortical neurons (to investigate initial neurite formation), as well as mature (21 days postplating) clusters of cortical neurons (to investigate the regenerative sprouting response following injury). We report that MT-III inhibited the initial formation of neurites by rat embryonic (E18) cortical neurons. This was based on both the percentage of neurite positive neurons and the number of neurites per neuron (45 and 30% inhibition, respectively). Neurite inhibition was only observed in the presence of adult rat brain extract, and was also reversible following replacement of MT-III-containing medium. MT-III inhibited the formation and growth of both axons and dendrites. Of more physiological significance, MT-III also inhibited the regenerative neurite sprouting response following axonal transection. The morphology of sprouting neurites was also altered, with the distal tip often ending in bulb-like structures. Based on these results, we propose that MT-III, in the presence of brain extract, is a potent inhibitor of neurite sprouting, and may be involved in abnormal sprouting potentially underlying both AD and epilepsy. © 2002 Elsevier Science (USA).

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Cellular nervous system
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the environmental sciences
UTAS Author:Chung, RS (Associate Professor Roger Chung)
UTAS Author:Vickers, JC (Professor James Vickers)
UTAS Author:Chuah, MI (Associate Professor Inn Chuah)
UTAS Author:Eckhardt, BL (Mr Bedrich Eckhardt)
UTAS Author:West, AK (Professor Adrian West)
ID Code:25132
Year Published:2002
Web of Science® Times Cited:44
Deposited By:Anatomy and Physiology
Deposited On:2002-08-01
Last Modified:2003-04-01

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