Traumatic brain injury induces biphasic upregulation of ApoE and ApoJ protein in rats.
Apolipoproteins play an important role in cell repair and have been found to increase shortly after traumatic brain injury (TBI). In addition, apolipoproteins reduce amyloid-beta (Abeta) accumulation in models of Alzheimer's disease. Considering that TBI induces progressive neurodegeneration including Abeta accumulation, we explored potential long-term changes in the gene and protein expression of apolipoproteins E and J (ApoE and J) over 6 months after injury. Anesthetized male Sprague-Dawley rats were subjected to parasagittal fluid-percussion brain injury and their brains were evaluated at 2, 4, 7, 14 days, and 1 and 6 months after TBI. In situ hybridization, Western blot, and immunohistochemical analysis demonstrated that although there was a prolonged upregulation in both the gene expression and protein concentration of ApoE and J after injury, these responses were uncoupled. Upregulation of ApoE and J mRNA expression lasted from 4 days to 1 month after injury. In contrast, a biphasic increase in protein concentration and number of immunoreactive cells for ApoE and ApoJ was observed, initially peaking at 2 days (i.e., before increased mRNA expression), returning to baseline by 2 weeks and then gradually increasing through 6 months postinjury. In addition, ApoE and J were found to colocalize with Abeta accumulation in neurons and astrocytes at 1-6 months after injury. Collectively, these data suggest that ApoE and J play a role in the acute sequelae of brain trauma and reemerge long after the initial insult, potentially to modulate progressive neurodegenerative changes.
Iwata
Akira
A
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6316, USA.
Browne
Kevin D
KD
Chen
Xiao-Han
XH
Yuguchi
Takamichi
T
Smith
Douglas H
DH
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D051152:Clusterin / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D051152:Clusterin; D005904:Glial Fibrillary Acidic Protein; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D012333:RNA, Messenger; D010751:Phosphopyruvate Hydratase