A role for the preoptic sleep-promoting system in absence epilepsy

Neurobiol Dis. 2009 Oct;36(1):126-41. doi: 10.1016/j.nbd.2009.07.005. Epub 2009 Jul 23.

Abstract

Absence epilepsy (AE) in humans and the genetic AE model in WAG/Rij rats are both associated with abnormalities in sleep architecture that suggest insufficiency of the sleep-promoting mechanisms. In this study we compared the functionality of sleep-active neuronal groups within two well-established sleep-promoting sites, the ventrolateral and median preoptic nuclei (VLPO and MnPN, respectively), in WAG/Rij and control rats. Neuronal activity was assessed using c-Fos immunoreactivity and chronic single-unit recording techniques. We found that WAG/Rij rats exhibited a lack of sleep-associated c-Fos activation of GABAergic MnPN and VLPO neurons, a lower percentage of MnPN and VLPO cells increasing discharge during sleep and reduced firing rates of MnPN sleep-active neurons, compared to non-epileptic rats. The role of sleep-promoting mechanisms in pathogenesis of absence seizures was assessed in non-epileptic rats using electrical stimulation and chemical manipulations restricted to the MnPN. We found that fractional activation of the sleep-promoting system in waking was sufficient to elicit absence-like seizures. Given that reciprocally interrelated sleep-promoting and arousal neuronal groups control thalamocortical excitability, we hypothesize that malfunctioning of sleep-promoting system results in impaired ascending control over thalamocortical rhythmogenic mechanisms during wake-sleep transitions thus favoring aberrant thalamocortical oscillations. Our findings suggest a pathological basis for AE-associated sleep abnormalities and a mechanism underlying association of absence seizures with wake-sleep transitions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / genetics
  • Action Potentials / physiology
  • Analysis of Variance
  • Animals
  • Cell Count / methods
  • Disease Models, Animal
  • Electric Stimulation / methods
  • Electroencephalography / methods
  • Electromyography
  • Epilepsy, Absence / genetics
  • Epilepsy, Absence / pathology*
  • Epilepsy, Absence / physiopathology*
  • Glutamate Decarboxylase / metabolism
  • Neurons / physiology
  • Preoptic Area / pathology
  • Preoptic Area / physiopathology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Mutant Strains
  • Rats, Wistar
  • Sleep / genetics
  • Sleep / physiology*
  • Sleep Deprivation / physiopathology
  • Wakefulness / genetics

Substances

  • Proto-Oncogene Proteins c-fos
  • Glutamate Decarboxylase