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

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 effec...

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Published inThe Journal of biological chemistry Vol. 288; no. 23; pp. 17042 - 17050
Main Authors Hawkins, Bridget E, Krishnamurthy, Shashirekha, Castillo-Carranza, Diana L, Sengupta, Urmi, Prough, Donald S, Jackson, George R, DeWitt, Douglas S, Kayed, Rakez
Format Journal Article
LanguageEnglish
Published United States American Society for Biochemistry and Molecular Biology 07.06.2013
Subjects
Animals
Brain Injuries - complications
Brain Injuries - metabolism
Brain Injuries - pathology
Brain Injuries - physiopathology
Cerebrospinal Fluid Pressure
Disease Models, Animal
Humans
Male
Molecular Bases of Disease
Phosphorylation
Protein Multimerization
Rats
Rats, Sprague-Dawley
tau Proteins - metabolism
Tauopathies - etiology
Tauopathies - metabolism
Tauopathies - pathology
Tauopathies - physiopathology
Tauopathies
Protein Misfolding
Traumatic Brain Injury
Protein Aggregation
Neurodegeneration
Tau
Tau Oligomers
Tau Aggregation
Protein Assembly
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Summary: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.
Bibliography:These authors contributed equally to this work.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M113.472746