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Metallothionein induces a regenerative reactive astrocyte phenotype via JAK/STAT and RhoA signalling pathways


Leung, YKJ and Pankhurst, M and Dunlop, SA and Ray, S and Dittmann, J and Eaton, ED and Palumaa, P and Sillard, R and Chuah, MI and West, AK and Chung, RS, Metallothionein induces a regenerative reactive astrocyte phenotype via JAK/STAT and RhoA signalling pathways , Experimental Neurology: A Journal of Neuroscience Research, 221, (1) pp. 98-106. ISSN 0014-4886 (2010) [Refereed Article]

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DOI: doi:10.1016/j.expneurol.2009.10.006


Following central nervous system injury, astrocytes rapidly respond by undergoing a stereotypical pattern of molecular and morphological alterations termed "reactive" astrogliosis. We have reported previously that metallothioneins (MTs) are rapidly expressed by reactive astrocytes and that their secretion and subsequent interaction with injured neurons leads to improved neuroregeneration. We now demonstrate that exogenous MT induces a reactive morphology and elevated GFAP expression in cultured astrocytes. Furthermore, these astrogliotic hallmarks were mediated via JAK/STAT and RhoA signalling pathways. However, rather than being inhibitory, MT induced a form of astrogliosis that was permissive to neurite outgrowth and which was associated with decreased chondroitin sulphate proteoglycan (CSPG) expression. The results suggest that MT has an important role in mediating permissive astrocytic responses to traumatic brain injury.

Item Details

Item Type:Refereed Article
Keywords:Traumatic brain injury, Astrogliosis, Regeneration
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Cellular nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Leung, YKJ (Dr Jacqueline Leung)
UTAS Author:Pankhurst, M (Mr Michael Pankhurst)
UTAS Author:Ray, S (Mrs Shannon Huskins)
UTAS Author:Dittmann, J (Mr Justin Dittmann)
UTAS Author:Eaton, ED (Dr Emma Eaton)
UTAS Author:Chuah, MI (Associate Professor Inn Chuah)
UTAS Author:West, AK (Professor Adrian West)
UTAS Author:Chung, RS (Associate Professor Roger Chung)
ID Code:64815
Year Published:2010
Web of Science® Times Cited:45
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-09-02
Last Modified:2011-04-29

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