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APP stimulates neural stem/progenitor cell proliferation by increasing cystatin C secretion. (Poster)


Hu, Y and Hung, AC and Cui, H and Dawkins, E and Foa, L and Young, KM and Small, DH, APP stimulates neural stem/progenitor cell proliferation by increasing cystatin C secretion. (Poster), 33rd Annual Meeting Australian Neuroscience Society, January, Melbourne, Australia (2013) [Conference Extract]

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The amyloid precursor protein has been well studied for its role in Alzheimerís disease. However, little is known about its normal function. In this study, we examined whether APP plays a role in neural stem or progenitor cell proliferation. Neural stem / progenitor cells (NSPCs) were cultured as neurospheres. We found that there was an increase in the proliferation of NSPCs derived from APP-overexpressing Tg2576 transgenic mice (P<0.05, n=7). However, NSPCs obtained from APP knockout mice (APP KO mice) had reduced proliferation rates (P<0.01, n=4). To examine if a secreted factor was responsible for the increased proliferation, the conditioned medium (CM) was collected from Tg2576, APP KO and wide-type neurosphere cultures and added into the neurosphere-derived cell cultures. CM from Tg2576 cultures stimulated neurosphere proliferation (P<0.05, n=5) compared to wild-type CM whereas CM from APP KO cultures had little effect on proliferation of neurosphere. To identify secreted molecules in the CM of Tg2576 cultures which can promote proliferation, the CM was analyzed for its effect on proliferation by immunoblotting and immunodepletion. Immunodepletion of APP from CM of Tg2576 did not reduce proliferation (P>0.05, n=4). Furthermore, recombinant APP did not stimulate proliferation. As cystatin C has been reported to stimulate neural stem cell proliferation, we examined the possibility that the secreted molecule may be cystatin C. Levels of cystatin C were higher in the CM of Tg2576 cells than in the CM of WT cells (P<0.05, n=5). Cystatin C was lower in the CM obtained from APP KO cultures (P<0.05, n=3). Immunodepletion of cystatin C from CM of Tg2576 culture decreased the effect on cell proliferation (P<0.05, n=4). The results demonstrate that APP stimulates NSPC proliferation, and that this effect is mediated via an increase in cystatin C secretion.

Item Details

Item Type:Conference Extract
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Hu, Y (Ms Ivy Hu)
UTAS Author:Hung, AC (Dr Amos Hung)
UTAS Author:Cui, H (Mr Hao Cui)
UTAS Author:Dawkins, E (Dr Edgar Dawkins)
UTAS Author:Foa, L (Professor Lisa Foa)
UTAS Author:Young, KM (Associate Professor Kaylene Young)
UTAS Author:Small, DH (Professor David Small)
ID Code:93543
Year Published:2013
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-08-07
Last Modified:2014-08-07

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