title: Traumatic brain injury induces biphasic upregulation of ApoE and ApoJ protein in rats.
abstract: 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.
authors.affiliation: Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6316, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Iwata
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Browne
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Chen
authors.forename: Takamichi
authors.initials: T
authors.lastname: Yuguchi
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Smith
mesh_terms: 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*
chemical_list: 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