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Absence of γ‐aminobutyric acid‐a receptor potentiation in central hypersomnolence disorders
Author(s) -
Dauvilliers Yves,
Evangelista Elisa,
Lopez Regis,
Barateau Lucie,
Jaussent Isabelle,
Cens Thierry,
Rousset Matthieu,
Charnet Pierre
Publication year - 2016
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24710
Subject(s) - long term potentiation , aminobutyric acid , neuroscience , psychology , medicine , receptor
Objective The pathophysiology of idiopathic hypersomnia (IH) remains unclear. Recently, cerebrospinal fluid (CSF)‐induced enhancement of γ‐aminobutyric acid (GABA)‐A receptor activity was found in patients with IH compared to controls. Methods Fifteen unrelated patients (2 males and 13 females) affected with typical IH, 12 patients (9 males and 3 females) with narcolepsy type 1, and 15 controls (9 males and 6 females) with unspecified hypersomnolence (n = 7) and miscellaneous neurological conditions (n = 8) were included. A lumbar puncture was performed in all participants to measure CSF hypocretin‐1 and GABA‐A response. We used a voltage‐clamp assay on Xenopus oocytes injected with the RNAs that encode the α 1 β 2 γ 2 or the α 2 β 2 γ 2 subunits of the human GABA‐A receptor. A sequence of 6 different applications (GABA, GABA/CSF, and CSF alone) with 2 to 4 oocytes per CSF sample was performed in a whole‐cell voltage‐clamp assay. Results Representative current traces from oocytes expressing human α 1 β 2 γ 2 or α 2 β 2 γ 2 GABA‐A receptors were recorded in response to 6 successive puffs of GABA diluted in the survival medium (SM), showing stable and reliable response. GABA puffs diluted in SM/CSF solution or SM/CSF solution alone showed no significant differences in the CSF of IH, narcolepsy, or control groups. No associations were found between GABA responses, demographic features, disease duration, or disease severity in the whole population or within groups. Interpretation Using the Xenopus oocyte assay, we found an absence of GABA‐A receptor potentiation with CSF from patients with central hypersomnolence disorders, with no significant differences between hypocretin‐deficient and non–hypocretin‐deficient patients compared to controls. Ann Neurol 2016;80:259–268

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