Downregulation of amyloid precursor protein (APP) expression following post-traumatic cyclosporin-A administration

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 non-impacted 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.

Original languageEnglish
Pages (from-to)1562-1572
Number of pages11
JournalJournal of Neurotrauma
Volume21
Issue number11
DOIs
Publication statusPublished - 1 Jan 2004

Keywords

  • Amyloid precursor protein
  • Cyclosporin-A
  • Head injury model
  • Immunocytochemistry
  • RT-PCR
  • Sheep
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Van Den Heuvel, C., Donkin, J. J., Finnie, J. W., Blumbergs, P. C., Kuchel, T., Koszyca, B., ... Vink, R. (2004). Downregulation of amyloid precursor protein (APP) expression following post-traumatic cyclosporin-A administration. Journal of Neurotrauma, 21(11), 1562-1572. https://doi.org/10.1089/0897715042441783