Quinolinic acid toxicity on orexin neurons blocked by gamma aminobutyric acid type A receptor stimulation

被引:9
作者
Katsuki, H [1 ]
Akaike, A [1 ]
机构
[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Sakyo Ku, Kyoto 6068501, Japan
关键词
excitotoxicity; hypocretin; hypothalamus; narcolepsy; neurodegeneration;
D O I
10.1097/00001756-200508010-00005
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Selective degeneration of hypothalamic orexin neurons, a hallmark of pathology in narcolepsy patients, is in part reproduced in hypothalamic slice cultures by application of an endogenous excitotoxin quinolinic acid. Depolarized membrane potential may be responsible for the vulnerability of orexin neurons to excitotoxicity We show that stimulation of gamma-aminobutyric acid type A receptors, which is known to hyperpolarize orexin neurons, by muscimol or isoguvacine potently inhibits quinolinic acid cytotoxicity on orexin neurons. In addition, the protective effect of gamma-aminobutyric acid and a gamma-aminobutyric acid uptake blocker nipecotic acid is abolished by gamma-aminobutyric acid type A antagonist picrotoxin. Norepinephrine and serotonin do not provide a neuroprotective effect. Thus, GABAergic inhibitory control may be a decisive factor regulating survival of orexin neurons under excitotoxic insults.
引用
收藏
页码:1157 / 1161
页数:5
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