title: Ketogenic diet treatment increases longevity in Kcna1-null mice, a model of sudden unexpected death in epilepsy.
abstract: Individuals with poorly controlled epilepsy have a higher risk for sudden unexpected death in epilepsy (SUDEP). With approximately one third of people with epilepsy not achieving adequate seizure control with current antiseizure drugs, there is a critical need to identify treatments that reduce risk factors for SUDEP. The Kcna1-null mutant mouse models risk factors and terminal events associated with SUDEP. In the current study, we demonstrate the progressive nature of epilepsy and sudden death in this model (mean age of mortality (± SEM), postnatal day [P] 42.8 ± 1.3) and tested the hypothesis that long-term treatment with the ketogenic diet (KD) will prolong the life of Kcna1-null mice. We found that the KD postpones disease progression by delaying the onset of severe seizures and increases the lifespan of these mutant mice by 47%. Future studies are needed to determine the mechanisms underlying the KD effects on longevity.
authors.affiliation: Department of Pharmacology, Creighton University School of Medicine, Omaha, Nebraska, U.S.A.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Simeone
authors.affiliation: Department of Pharmacology, Creighton University School of Medicine, Omaha, Nebraska, U.S.A.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Matthews
authors.affiliation: Departments of Pediatrics, Clinical Neurosciences, Physiology & Pharmacology, Alberta Children's Hospital Research Institute for Child and Maternal Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
authors.affiliation: Department of Pharmacology, Creighton University School of Medicine, Omaha, Nebraska, U.S.A.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Simeone
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose; D003645:Death, Sudden / Q000209:etiology*; D055423:Diet, Ketogenic / Q000379:methods*; D004195:Disease Models, Animal; D018450:Disease Progression; D004569:Electroencephalography; D004827:Epilepsy / Q000150:complications* / Q000235:genetics*; D051662:Kv1.1 Potassium Channel / Q000172:deficiency* / Q000235:genetics; D008136:Longevity / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D001786:Blood Glucose; C496947:Kcna1 protein, mouse; D051662:Kv1.1 Potassium Channel; D020155:3-Hydroxybutyric Acid
keywords: Disease progression; Kv1.1 knockout; Mortality; Seizures; Survival