期刊
BRAIN RESEARCH
卷 1451, 期 -, 页码 87-99出版社
ELSEVIER
DOI: 10.1016/j.brainres.2012.02.045
关键词
Amyloid precursor protein; Caspase-3; GAP-43; sAPP alpha; Synaptophysin; Traumatic brain injury
资金
- Brain Foundation
- Neurological Research Foundation
The amyloid precursor protein (APP) increases following traumatic brain injury (TBI), although the functional significance of this remains unclear largely because the functions of the subsequent APP metabolites are so different: A beta is neurotoxic whilst sAPP alpha is neuroprotective. To investigate this further, APP wildtype and knockout mice were subjected to mild diffuse TBI and their outcomes compared. APP knockout mice displayed significantly worse cognitive and motor deficits, as demonstrated by the Barnes Maze and rotarod respectively, than APP wildtype mice. This was associated with a significant increase in hippocampal and cortical cell loss, as well as axonal injury, in APP knockout mice and an impaired neuroreparative response as indicated by diminished GAP-43 immunoreactivity when compared to APP wildtype mice. This study is the first to demonstrate that endogenous APP is beneficial following mild TBI, suggesting that the upregulation of APP observed following injury is an acute protective response. (C) 2012 Elsevier B.V. All rights reserved.
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