title: Norepinephrine is required for the anticonvulsant effect of the ketogenic diet.
abstract: Ketogenic diet (KD) is a high fat, low carbohydrate diet used to treat children with epilepsy that are refractory to conventional antiepileptic drugs (AEDs). The anticonvulsant mechanism of the KD is unknown. To determine if the noradrenergic system has a role in mediating the anticonvulsant action of the KD, dopamine beta-hydroxylase knockout (Dbh -/-) mice that lack norepinephrine (NE) and Dbh +/- littermates that have normal NE content were fed either a standard rodent chow or the KD. When exposed to the convulsant flurothyl, Dbh +/- mice fed the KD had significantly longer latencies to myoclonic jerk (MJ) and generalized clonic-tonic (CT) seizures than Dbh +/- mice fed normal chow. In contrast, Dbh -/- mice fed the KD had seizure latencies to both MJ and CT comparable to Dbh -/- mice fed normal chow. These results suggest that an intact, functional noradrenergic nervous system is required for the KD to exert an anticonvulsant effect.
authors.affiliation: Geriatric Research, Education and Clinical Center (GRECC) (182B), VA Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108, USA. szot@u.washington.edu
authors.forename: P
authors.initials: P
authors.lastname: Szot
authors.forename: D
authors.initials: D
authors.lastname: Weinshenker
authors.forename: J M
authors.initials: JM
authors.lastname: Rho
authors.forename: T W
authors.initials: TW
authors.lastname: Storey
authors.forename: P A
authors.initials: PA
authors.lastname: Schwartzkroin
mesh_terms: D000818:Animals; D003292:Convulsants; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000627:therapeutic use; D004041:Dietary Fats / Q000008:administration & dosage* / Q000627:therapeutic use; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004827:Epilepsy / Q000139:chemically induced / Q000178:diet therapy*; D005481:Flurothyl; D007657:Ketone Bodies / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009638:Norepinephrine / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology
chemical_list: D003292:Convulsants; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007657:Ketone Bodies; D005481:Flurothyl; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine