Rapid accumulation of endogenous tau oligomers in a rat model of traumatic brain injury: possible link between traumatic brain injury and sporadic tauopathies

J Biol Chem. 2013 Jun 7;288(23):17042-17050. doi: 10.1074/jbc.M113.472746. Epub 2013 Apr 30.

Abstract

Traumatic brain injury (TBI) is a serious problem that affects millions of people in the United States alone. Multiple concussions or even a single moderate to severe TBI can also predispose individuals to develop a pathologically distinct form of tauopathy-related dementia at an early age. No effective treatments are currently available for TBI or TBI-related dementia; moreover, only recently has insight been gained regarding the mechanisms behind their connection. Here, we used antibodies to detect oligomeric and phosphorylated Tau proteins in a non-transgenic rodent model of parasagittal fluid percussion injury. Oligomeric and phosphorylated Tau proteins were detected 4 and 24 h and 2 weeks post-TBI in injured, but not sham control rats. These findings suggest that diagnostic tools and therapeutics that target only toxic forms of Tau may provide earlier detection and safe, more effective treatments for tauopathies associated with repetitive neurotrauma.

Keywords: Neurodegeneration; Protein Aggregation; Protein Assembly; Protein Misfolding; Tau; Tau Aggregation; Tau Oligomers; Tauopathies; Traumatic Brain Injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries / complications
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Cerebrospinal Fluid Pressure
  • Disease Models, Animal
  • Humans
  • Male
  • Phosphorylation
  • Protein Multimerization*
  • Rats
  • Rats, Sprague-Dawley
  • Tauopathies / etiology
  • Tauopathies / metabolism*
  • Tauopathies / pathology
  • Tauopathies / physiopathology
  • tau Proteins / metabolism*

Substances

  • Mapt protein, rat
  • tau Proteins