期刊
BRAIN RESEARCH
卷 1378, 期 -, 页码 137-143出版社
ELSEVIER
DOI: 10.1016/j.brainres.2010.12.077
关键词
Amyloid precursor protein; Growth factor like domain; E2 domain; sAPP alpha; Traumatic brain injury
资金
- Brain Foundation (Australia)
- Neurosurgical Research Foundation (Australia)
The amyloid precursor protein (APP) is known to increase following traumatic brain injury (TBI). This increase in levels of APP may be deleterious to outcome due to the production of neurotoxic A beta. Conversely, this upregulation may be beneficial as cleavage of APP via the alternative non-amyloidogenic pathway produces the soluble alpha form of APP (sAPP alpha), which is known to have many neuroprotective and neurotrophic functions. Indeed it has previously been shown that treatment with sAPP alpha following a diffuse injury in rats improves outcome. However, the exact location within the sAPP alpha molecule which contains this neuroprotective activity has yet to be determined. The sAPP alpha peptide can consist of up to 6 domains, with the main isoform in the brain missing the 4th and 5th. Of the remaining domains, the D1 and D6a domains seem the most likely as they have been shown to have beneficial actions in vitro. This present study examined the effects of in vivo posttraumatic administration via an intracerebroventricular injection of the D1, 02 and D6a domains of sAPP alpha on outcome following moderate-impact acceleration TBI in rats. While treatment with either the D1 or D6a domains was found to significantly improve motor and cognitive outcome, as assessed on the rotarod and Y maze, treatment with the D2 domain had no effect. Furthermore axonal injury was reduced in D1 and D6a domain treated animals, but not those that received the D2 domain. As the D1 and D6a domains contain a heparin binding region while the 02 domain does not, this suggests that sAPP alpha mediates its neuroprotective response through its ability to bind to heparin sulfate proteoglycans. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.
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