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

• Published in: Epilepsia (Copenhagen) 2017-03, Vol.58 (3), p.467-475
• Main Authors: Sánchez‐Elexpuru, Gentzane, Serratosa, José M., Sánchez, Marina P.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - therapeutic use; Anxiety - drug therapy; Anxiety - etiology; Convulsants - toxicity; Disease; Disease Models, Animal; Dual-Specificity Phosphatases - deficiency; Dual-Specificity Phosphatases - genetics; Epilepsy; Epm2b−/− mouse; Exploratory Behavior - drug effects; Glial Fibrillary Acidic Protein - metabolism; Lafora bodies; Lafora Disease - chemically induced; Lafora Disease - complications; Lafora Disease - drug therapy; Lafora Disease - genetics; Memory Disorders - drug therapy; Memory Disorders - etiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Movement Disorders - drug therapy; Movement Disorders - etiology; Oxidative stress; Pentylenetetrazole - toxicity; Phosphopyruvate Hydratase - metabolism; Psychomotor Performance - drug effects; Recognition (Psychology) - drug effects; Rodents; Selenic Acid - therapeutic use; Sodium; Sodium selenate; Ubiquitin-Protein Ligases - deficiency; Ubiquitin-Protein Ligases - genetics
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/epi.13656

Summary 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.