title: Ketogenic diet treatment abolishes seizure periodicity and improves diurnal rhythmicity in epileptic Kcna1-null mice.
abstract: BACKGROUND
  Seizures are known to perturb circadian rhythms in humans as well as in animal models of epilepsy. However, it is unknown whether treatment of the underlying epilepsy restores normal biologic rhythms. We asked whether: (1) seizure activity is characterized by diurnal rhythmicity, (2) chronically epileptic mice exhibit impaired rest-activity rhythms, and (3) treatment with the anticonvulsant ketogenic diet (KD) improves such perturbations.
  
  
  METHODS
  Chronically epileptic Kcna1-null mice were fed either a standard diet (SD) or KD for 4 weeks and subjected to continuous video-EEG (electroencephalography) and actigraphy monitoring for 3-5 days to assess seizure activity and rest-activity cycles.
  
  
  RESULTS
  Seizure activity in Kcna1-null mice demonstrated diurnal rhythmicity, peaking at zeitgeber (ZT)2.30 +/- 1.52. Rest-activity rhythms of epileptic mice were significantly disrupted. Whereas locomotor activity for wild-type mice peaked at ZT15.45 +/- 0.28 (ZT14:26-ZT16:51), peak activity of epileptic mice was more unpredictable, occurring over a 12.4 h range (ZT06:33-ZT18:57). In six of nine epileptic mice, peak activity was delayed to ZT17.42 +/- 0.38, whereas peak activity was advanced to ZT10.00 +/- 1.26 in the remaining mice. Treatment with the KD abolished seizure periodicity and restored the rest-activity rhythm to values resembling those of wild-type mice (i.e., activity peaking at ZT16.73 +/- 0.67).
  
  
  CONCLUSIONS
  Kcna1-null mice experience seizures with 24-h periodicity and impaired circadian behavior. KD reduces the number and periodicity of seizures and restores normal behavioral rhythms, suggesting that this nonpharmacologic therapy may benefit biologic rhythm disturbances in epileptic patients.
authors.affiliation: Barrow Neurological Institute and St. Joseph's Medical Center, Neurology Research, Phoenix, Arizona 85013, USA.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Fenoglio-Simeone
authors.forename: Julianne C
authors.initials: JC
authors.lastname: Wilke
authors.forename: Heather L
authors.initials: HL
authors.lastname: Milligan
authors.forename: Charles N
authors.initials: CN
authors.lastname: Allen
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
authors.forename: Rama K
authors.initials: RK
authors.lastname: Maganti
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D055423:Diet, Ketogenic / Q000379:methods*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000178:diet therapy; D006801:Humans; D051662:Kv1.1 Potassium Channel / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics*; D010507:Periodicity; D012640:Seizures / Q000178:diet therapy*; D014743:Videotape Recording
chemical_list: C496947:Kcna1 protein, mouse; D051662:Kv1.1 Potassium Channel