Downregulation of amyloid precursor protein (APP) expression following post-traumatic cyclosporin-A administration
Date
2004
Authors
Van Den Heuvel, C.
Donkin, J.
Finnie, J.
Blumbergs, P.
Kuchel, T.
Koszyca, B.
Manavis, J.
Jones, N.
Reilly, P.
Vink, R.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Neurotrauma, 2004; 21(11):1562-1572
Statement of Responsibility
Corinna Van Den Heuvel, James J. Donkin, John W. Finnie, Peter C. Blumbergs, Tim Kuchel, Barbara Koszyca, Jim Manavis, Nigel R. Jones, Peter L. Reilly, Robert Vink
Conference Name
Abstract
The aim of these studies was to assess and quantitate the effects of cyclosporin-A (CyA) on brain APP messenger RNA and neuronal perikaryal APP antigen expression following controlled focal head impact in sheep. Impact results in a significant increase in both APP mRNA and neuronal perikaryal APP antigen expression. Post-traumatic administration of CyA (intrathecal 10 mg/kg) resulted in a reduction in APP mRNA and neuronal perikaryal antigen expression. At 2 h postinjury, CyA treatment caused a statistically significant (p < 0.05) 1.3 +/- 0.1-fold decrease in APP mRNA in the central gray matter of impacted sheep compared to untreated impacted sheep. A more profound reduction in APP mRNA synthesis (1.6 +/- 0.2 fold) was evident at 6 h (p < 0.05). The mean percentage brain area with APP immunoreactive neuronal perikarya at 6 h post-injury was 94.5% in untreated impacted animals, 10.0% in CyA-treated impacted animals, 5.5% in untreated nonimpacted animals, and 6% in CyA-treated non-impacted controls. These results demonstrate that CyA has a downregulatory effect on increased APP expression caused by TBI.
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Dissertation Note
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Copyright © 2004 Mary Ann Liebert, Inc.