Traumatic brain injury induces biphasic upregulation of ApoE and ApoJ protein in rats

J Neurosci Res. 2005 Oct 1;82(1):103-14. doi: 10.1002/jnr.20607.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Blotting, Western / methods
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Clusterin / genetics
  • Clusterin / metabolism*
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Low Density Lipoprotein Receptor-Related Protein-1 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-2 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-2 / metabolism
  • Male
  • Phosphopyruvate Hydratase / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Up-Regulation / physiology*

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Clusterin
  • Glial Fibrillary Acidic Protein
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Low Density Lipoprotein Receptor-Related Protein-2
  • RNA, Messenger
  • Phosphopyruvate Hydratase