Downregulation of amyloid precursor protein (APP) expression following post-traumatic cyclosporin-A administration.
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.
Van Den Heuvel
Corinna
C
Department of Pathology, University of Adelaide, Adelaide, South Australia, Australia. corinna.vandenheuvel@adelaide.edu.au
Donkin
James J
JJ
Finnie
John W
JW
Blumbergs
Peter C
PC
Kuchel
Tim
T
Koszyca
Barbara
B
Manavis
Jim
J
Jones
Nigel R
NR
Reilly
Peter L
PL
Vink
Robert
R
D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D007278:Injections, Spinal; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D012756:Sheep; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016572:Cyclosporine