Sodium selenate treatment improves symptoms and seizure susceptibility in a malin-deficient mouse model of Lafora disease.

Abstract

OBJECTIVE:

To search for new therapies aimed at ameliorating the neurologic symptoms and epilepsy developing in patients with Lafora disease.

METHODS:

Lafora disease is caused by loss-of-function mutations in either the EPM2A or EPM2B genes. Epm2a-/- and Epm2b-/- mice display neurologic and behavioral abnormalities similar to those found in patients. Selenium is a potent antioxidant and its deficiency has been related to the development of certain diseases, including epilepsy. In this study, we investigated whether sodium selenate treatment improved the neurologic alterations and the hyperexcitability present in the Epm2b-/- mouse model.

RESULTS:

Sodium selenate ameliorates some of the motor and memory deficits and the sensitivity observed with pentylenetetrazol (PTZ) treatments in Epm2b-/- mice. Neuronal degeneration and gliosis were also diminished after sodium selenate treatment.

SIGNIFICANCE:

Sodium selenate could be beneficial for ameliorating some symptoms that present in patients with Lafora disease.

• Authors: Gentzane Sánchez-Elexpuru, José M Serratosa, Marina P Sánchez
• Journal: Epilepsia (Epilepsia) Vol. 58 Issue 3 Pg. 467-475 (03 2017) ISSN: 1528-1167 [Electronic] United States
• PMID: 28098937 (Publication Type: Journal Article)
• Copyright: Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Chemical References

• Antioxidants
• Convulsants
• Glial Fibrillary Acidic Protein
• NHLRC1 protein, mouse
• Ubiquitin-Protein Ligases
• Dual-Specificity Phosphatases
• Epm2a protein, mouse
• Protein Tyrosine Phosphatases, Non-Receptor
• Phosphopyruvate Hydratase
• Selenic Acid
• Pentylenetetrazole

Topics

• Animals
• Antioxidants (therapeutic use)
• Anxiety (drug therapy, etiology)
• Convulsants (toxicity)
• Disease Models, Animal
• Dual-Specificity Phosphatases (deficiency, genetics)
• Exploratory Behavior (drug effects)
• Glial Fibrillary Acidic Protein (metabolism)
• Lafora Disease (chemically induced, complications, drug therapy, genetics)
• Memory Disorders (drug therapy, etiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Movement Disorders (drug therapy, etiology)
• Pentylenetetrazole (toxicity)
• Phosphopyruvate Hydratase (metabolism)
• Protein Tyrosine Phosphatases, Non-Receptor
• Psychomotor Performance (drug effects)
• Recognition, Psychology (drug effects)
• Selenic Acid (therapeutic use)
• Ubiquitin-Protein Ligases (deficiency, genetics)