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Adelaide Research and Scholarship : Schools and Disciplines : School of Medical Sciences : Pathology : Pathology publications

Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/73547

Type: Journal article
Title: sAPPα rescues deficits in amyloid precursor protein knockout mice following focal traumatic brain injury
Other Titles: sAPPalpha rescues deficits in amyloid precursor protein knockout mice following focal traumatic brain injury
Author: Corrigan, F.
Vink, R.
Blumbergs, P.
Masters, C.
Cappai, R.
Van Den Heuvel, C.
Citation: Journal of Neurochemistry, 2012; 122(1):208-220
Publisher: Blackwell Publishing Ltd
Issue Date: 2012
ISSN: 0022-3042
1471-4159
Statement of
Responsibility: 
Frances Corrigan, Robert Vink, Peter C. Blumbergs, Colin L. Masters, Roberto Cappai, Corinna van den Heuvel
Abstract: The amyloid precursor protein (APP) is thought to be neuroprotective following traumatic brain injury (TBI), although definitive evidence at moderate to severe levels of injury is lacking. In the current study, we investigated histological and functional outcomes in APP-/- mice compared with APP+/+ mice following a moderate focal injury, and whether administration of sAPPα restored the outcomes in knockout animals back to the wildtype state. Following moderate controlled cortical impact injury, APP-/- mice demonstrated greater impairment in motor and cognitive outcome as determined by the ledged beam and Barnes Maze tests respectively (p < 0.05). This corresponded with the degree of neuronal damage, with APP-/- mice having significantly greater lesion volume (25.0 ± 1.6 vs. 20.3 ± 1.6%, p < 0.01) and hippocampal damage, with less remaining CA neurons (839 ± 245 vs. 1353 ± 142 and 1401 ± 263). This was also associated with an impaired neuroreparative response, with decreased GAP-43 immunoreactivity within the cortex around the lesion edge compared with APP+/+ mice. The deficits observed in the APP-/- mice related to a lack of sAPPα, as treatment with exogenously added sAPPα post-injury improved APP-/- mice histological and functional outcome to the point that they were no longer significantly different to APP+/+ mice (p < 0.05). This study shows that endogenous APP is potentially protective at moderate levels of TBI, and that this neuroprotective activity is related to the presence of sAPPα. Importantly, it indicates that the mechanism of action of exogenously added sAPPα is independent of the presence of endogenous APP.
Keywords: amyloid precursor protein; sAPPα; traumatic brain injury
Rights: © 2012 The Authors.
RMID: 0020120041
DOI: 10.1111/j.1471-4159.2012.07761.x
Appears in Collections:Pathology publications
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