Sodium selenate retards epileptogenesis in acquired epilepsy models reversing changes in protein phosphatase 2A and hyperphosphorylated tau.
Brain
; 139(Pt 7): 1919-38, 2016 07.
Article
in En
| MEDLINE
| ID: mdl-27289302
ABSTRACT
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Brain
/
Tau Proteins
/
Disease Models, Animal
/
Epilepsy
/
Protein Phosphatase 2
/
Selenic Acid
/
Anticonvulsants
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Brain
Year:
2016
Type:
Article
Affiliation country:
Australia