Sodium selenate, a protein phosphatase 2A activator, mitigates hyperphosphorylated tau and improves repeated mild traumatic brain injury outcomes

Xin L. Tan, David K. Wright, Shijie Liu, Christopher Hovens, Terence J. O'Brien, Sandy R. Shultz

Research output: Contribution to journalArticleResearchpeer-review

57 Citations (Scopus)


Mild traumatic brain injuries may result in cumulative brain damage and neurodegenerative disease. To date, there is no pharmaceutical intervention known to prevent these consequences. Hyperphosphorylated tau has been associated in this process, and protein phosphatase 2A 55 kDa regulatory B subunit (PP2A/PR55) - the major tau phosphatase - is decreased after a brain insult. Sodium selenate up-regulates PP2A/PR55 and dephosphorylates tau, and may hold promise as a treatment in the mild brain injury setting. Here we investigated sodium selenate treatment in rats given repeated mild traumatic brain injuries. Rats were given three mild fluid percussion injuries or three sham-injuries, and treated with sodium selenate (1 mg/kg/day) or saline-vehicle for three months before undergoing behavioral testing, MRI, and post-mortem analysis of brain tissue. Repeated mild traumatic brain injuries increased the phosphorylation of tau and decreased PP2A/PR55, whilst inducing brain atrophy and cognitive and sensorimotor deficits. Sodium selenate treatment increased PP2A/PR55, and decreased tau phosphorylation, brain damage, and cognitive and motor impairments in rats given repeated mild traumatic brain injuries. Our findings implicate PP2A/PR55 and tau as important mechanisms in the pathophysiological aftermath of repeated mild brain traumas, and support sodium selenate as a novel and translatable treatment for these common injuries.

Original languageEnglish
Pages (from-to)382-393
Number of pages12
Publication statusPublished - 1 Sept 2016
Externally publishedYes


  • chronic traumatic encephalopathy
  • concussion
  • diffusion tensor imaging
  • MRI
  • tauopathy
  • traumatic brain injury

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