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

NEUROBIOLOGY OF DISEASE

卷:36

Article

Suntsova, N.^1,2,5  Kumar, S.^1,3,6  Guzman-Marin, R.⁴  Alam, M. N.^1,2  Szymusiak, R.^1,3  McGinty, D.^1,2 

[1] VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA

[2] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA

[5] So Fed Univ, AB Kogan Res Inst Neurocybernet, Rostov Na Donu 344091, Russia

[6] Univ Patna, Dept Zool, Patna 800005, Bihar, India

关键词: Absence epilepsy;    Spike-wave discharges;    Sleep;    Median preoptic nucleus;    Ventrolateral preoptic nucleus;    GABAergic neurons;    c-Fos;    Neuronal activity;    WAG/Rij rats;   

DOI  :  10.1016/j.nbd.2009.07.005

来源: Elsevier

【 摘 要 】

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. Published by Elsevier Inc.

【 授权许可】

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