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

doi:10.1093/brain/aww116

Paper

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

Published Jul 1, 2016 · Shijie Liu, P. Zheng, David K. Wright

Brain : a journal of neurology

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98

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0

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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.

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Animal Study

Rigorous Journal

Highly Cited

Study Snapshot

Sodium selenate effectively reduces epileptogenesis in rat models by targeting protein phosphatase 2A and tau hyperphosphorylation, offering potential as an anti-epileptogenic therapy.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

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

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References

Metabolic crisis occurs with seizures and periodic discharges after brain trauma

Early post-traumatic seizures and pseudoperiodic discharges may be linked to metabolic crisis, suggesting potential therapeutic targets for treating metabolic crisis after brain trauma.

Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model

Z944, a T-type calcium channel antagonist, delays the progression of amygdala kindling in a temporal lobe epilepsy model, potentially offering a new therapeutic intervention for epilepsy treatment.

Sodium selenate reduces hyperphosphorylated tau and improves outcomes after traumatic brain injury.

Sodium selenate treatment reduces hyperphosphorylated tau and improves outcomes after traumatic brain injury in rats, suggesting potential as a novel traumatic brain injury therapy.

The challenge and promise of anti-epileptic therapy development in animal models

Anti-epileptic therapy development in animal models has led to effective treatments, but more research is needed to address unmet therapeutic needs and prevent epilepsy development in at-risk patients.

Granulocyte-macrophage colony-stimulating factor is neuroprotective in experimental traumatic brain injury.

GM-CSF may have significant protective properties in the chronic sequelae of experimental traumatic brain injury, suggesting further research is warranted.

Citations

The potential therapeutic role of berberine in treating epilepsy focusing on temporal lobe epilepsy: State of art and ongoing perspective

Berberine shows potential in treating refractory epilepsy and temporal lobe epilepsy, with its molecular mechanism still unclear.

Pharmacokinetics and brain uptake of sodium selenate and selenium in naïve rats and a lateral fluid percussion injury rat model

Sodium selenate shows potential in preventing post-traumatic epilepsy by activating protein phosphatase 2A and reducing phosphorylated tau protein in a lateral fluid percussion injury rat model.

Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer-like neuropathology in 5×FAD mice

Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer's disease-like neuropathology in 5FAD mice, partially regulated by the ERK-DAPK pathway.

A spike is a spike: On the universality of spike features in four epilepsy models

Epileptic spikes have the same shape and frequency characteristics in different animal models of generalized epilepsy, despite differences in recording sites and location.

Enhanced Fyn-tau and NR2B-PSD95 interactions in epileptic foci in experimental models and human epilepsy

Fyn-tau and NR2B-PSD95 interactions play a role in seizure-induced brain pathology, and blocking these interactions could modify epilepsy progression.

A comparison of the antiepileptogenic efficacy of two rationally chosen multitargeted drug combinations in a rat model of posttraumatic epilepsy

A combination of LEV, ATV, and ceftriaxone effectively prevents post-traumatic epilepsy in rats, while TC-001 partially prevents seizures in a rat model after TBI.

Fluoxetine accelerates epileptogenesis and magnifies disease severity in a rat model of acquired epilepsy.

Fluoxetine accelerates epileptogenesis and magnifies epilepsy severity in a rat model of acquired epilepsy, suggesting caution in prescribing SSRI antidepressants to people at risk of developing epilepsy.