Psychosine blocks quisqualate-induced glutamate excitotoxicity in hippocampal CA sector neurons.
Psychosine blocks quisqualate-induced glutamate excitotoxicity in hippocampal CA sector neurons.
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Psychosine 可阻断海马 CA 区神经元中由君子草酸诱导的谷氨酸兴奋性毒性。
DOI：
10.1016/s0006-8993(98)00508-3
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发表时间：
1998
期刊：
影响因子：
2.9
通讯作者：
Rosenberg,A
中科院分区：
文献类型：
--
作者：
Hodgson,DM;Taylor,AN;Zhang,Z;Rosenberg,A
使君子酸是第1组代谢型谷氨酸受体（mGluR）的有效特异性激动剂，其在分子信号转导机制中激活G蛋白偶联磷脂酶C（PLC），从而升高细胞质Ca 2+，并且当过量时，损伤海马神经元。Psychosine（β-半乳糖基鞘氨醇）是一种天然存在于神经组织中的阳离子溶血鞘脂，可剂量依赖性地抑制代谢型α1-肾上腺素能受体信号诱导的体外培养大鼠脑星形胶质细胞PLC活化。在本研究中，我们已经测试了在体内的神经保护作用，在大鼠模型中的谷氨酸兴奋毒性诱导的脑室内（i. c. v.）quisqualate的用法一个亚致死的i. c. v.剂量的使君子酸引起的事件的长期运动不能和惊厥，和海马CA 1和CA 3区的锥体神经元的重大损害，但不齿状回的颗粒细胞神经元。预先输注精神碱大大减弱了使君子诱导的行为，并完全防止了脆弱的海马神经元使君子的破坏。Psychosine可能被证明在预防神经退行性疾病中是有用的，这些疾病是由密集的海马1组mGluR刺激引起的。
Quisqualate is a potent specific agonist for Group 1 metabotropic glutamate receptors (mGluR's), that activate G protein-coupled phospholipase C (PLC) in a molecular signal-transduction mechanism that raises cytoplasmic Ca2+and, when excessive, damages hippocampal neurons. Psychosine (β-galactosylsphingosine), a cationic lysosphingolipid occurring naturally in nervous tissues, dose-dependently inhibited PLC activation induced by metabotropic α1-adrenergic receptor signaling in cultured rat brain astrocytes in vitro. In the present study, we have tested neuroprotective efficacy of psychosine in vivo, in a rat model of glutamate excitotoxicity induced by intracerebroventricular (i.c.v.) administration of quisqualate. A sublethal i.c.v. dose of quisqualate caused episodes of prolonged akinesia and convulsions, and major damage to pyramidal neurons of the hippocampal CA1 and CA3 sector, but not to granule cell neurons of the dentate gyrus. Prior infusion of psychosine greatly attenuated quisqualate-induced behaviors, and fully prevented destruction by quisqualate of vulnerable hippocampal neurons. Psychosine may prove useful in prophylaxis of neurodegenerative disorders that arise from intensive hippocampal Group 1 mGluR stimulation.