Changes in expression of amyloid precursor protein and interleukin-1beta after experimental traumatic brain injury in rats.
There is increasing evidence linking neurodegenerative mechanisms in Alzheimer's disease (AD) and traumatic brain injury (TBI), including increased production of amyloid precursor protein (APP), and amyloid-beta (Abeta) peptide. In vitro data indicate that expression of APP may be regulated in part by the inflammatory cytokine IL-1beta. To further investigate the mechanisms involved, we measured APP and IL-1beta protein levels and examined immunohistochemical localization of APP in brain tissue from rats subjected to controlled cortical impact (CCI) injury. Animals were examined at time intervals ranging from 3 h to 4 weeks after TBI. The 24-h time point revealed a dramatic increase in APP immunoreactivity, detected with both N- and C-terminal antibodies, in the hippocampus and cortex ipsilateral to injury. This finding was sustained up to 3 days post-injury. At these early time points, APP increase was particularly robust in the white matter axonal tracts. By 14 days after injury, APP immunoreactivity was not significantly different from sham controls in cortex, but remained slightly elevated in hippocampus. Western blot data corroborated early increases in hippocampal and cortical APP in injured versus control animals. Despite profound APP changes, no Abeta deposits were observed at any time after injury. Hippocampal and cortical IL-1beta increases were even more robust, with IL-1beta levels peaking by 6 h post-injury and returning to baseline by 24-72 h. Our results demonstrate that both APP and IL-1beta are rapidly elevated after injury. Because of the rapidity in the IL-1beta peak increase, it may serve a role in regulation of APP expression after TBI.
Ciallella
John R
JR
Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Ikonomovic
Milos D
MD
Paljug
William R
WR
Wilbur
Yetta I
YI
Dixon
C Edward
CE
Kochanek
Patrick M
PM
Marion
Donald W
DW
DeKosky
Steven T
ST
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; D007375:Interleukin-1; D010446:Peptide Fragments