Sodium selenate retards epileptogenesis in acquired epilepsy models reversing changes in protein phosphatase 2A and hyperphosphorylated tau

Brain. 2016 Jul;139(Pt 7):1919-38. doi: 10.1093/brain/aww116. Epub 2016 Jun 11.


There are no treatments in clinical practice known to mitigate the neurobiological processes that convert a healthy brain into an epileptic one, a phenomenon known as epileptogenesis. Downregulation of protein phosphatase 2A, a protein that causes the hyperphosphorylation of tau, is implicated in neurodegenerative diseases commonly associated with epilepsy, such as Alzheimer's disease and traumatic brain injury. Here we used the protein phosphatase 2A activator sodium selenate to investigate the role of protein phosphatase 2A in three different rat models of epileptogenesis: amygdala kindling, post-kainic acid status epilepticus, and post-traumatic epilepsy. Protein phosphatase 2A activity was decreased, and tau phosphorylation increased, in epileptogenic brain regions in all three models. Continuous sodium selenate treatment mitigated epileptogenesis and prevented the biochemical abnormalities, effects which persisted after drug withdrawal. Our studies indicate that limbic epileptogenesis is associated with downregulation of protein phosphatase 2A and the hyperphosphorylation of tau, and that targeting this mechanism with sodium selenate is a potential anti-epileptogenic therapy.

Keywords: MRI; PR55; animal model; epilepsy; traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / physiopathology
  • Brain Injuries, Traumatic / complications
  • Disease Models, Animal*
  • Electroencephalography
  • Epilepsy / chemically induced
  • Epilepsy / drug therapy
  • Epilepsy / etiology
  • Epilepsy / metabolism*
  • Excitatory Amino Acid Agonists / pharmacology
  • Kainic Acid / pharmacology
  • Kindling, Neurologic
  • Magnetic Resonance Imaging
  • Male
  • Phosphorylation
  • Protein Phosphatase 2 / drug effects
  • Protein Phosphatase 2 / metabolism*
  • Rats
  • Rats, Wistar
  • Selenic Acid / pharmacology*
  • tau Proteins / drug effects
  • tau Proteins / metabolism*


  • Anticonvulsants
  • Excitatory Amino Acid Agonists
  • tau Proteins
  • Ppp2r2a protein, rat
  • Protein Phosphatase 2
  • Selenic Acid
  • Kainic Acid