Lysosphingomyelin prevents behavioral aberrations and hippocampal neuron loss induced by the metabotropic glutamate receptor agonist quisqualate.
Lysosphingomyelin prevents behavioral aberrations and hippocampal neuron loss induced by the metabotropic glutamate receptor agonist quisqualate.
复制标题
溶血鞘磷脂可防止由代谢型谷氨酸受体激动剂使君子兰引起的行为失常和海马神经元损失。
DOI：
10.1016/s0278-5846(99)00047-0
复制
发表时间：
1999
影响因子：
5.6
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
1. 兴奋性神经递质谷氨酸对脑神经细胞的过度兴奋会诱发一系列事件，导致细胞内钙离子增加、神经元变性和死亡。2. 最近的体外研究表明，大脑中天然的阳离子两亲性物质溶鞘磷脂可能通过抑制由代谢性谷氨酸受体过度兴奋引起的磷酸腺苷酸酶- c过度激活来预防神经元变性。3. 本研究在谷氨酸兴奋性毒性大鼠模型中验证了后者的发现。脑室内（icv）给药1组代谢性谷氨酸受体（mGluR）激动剂（quisqualate）会引起癫痫发作、运动障碍、海马锥体细胞树突状微管相关蛋白-2的破坏以及海马CA区神经元的主要损失。4. 预防性的icv输注溶磷脂能有效地减弱这些准质量诱导的行为并防止神经元变性。5. 溶鞘磷脂可能在临床中用于缓解进展型1组mglur诱导的海马认知和运动障碍，包括阿尔茨海默病、脑癫痫和中风。
1. Excessive excitation of brain neurons by the excitatory neurotransmitter, glutamate, induces a cascade of events leading to increased intracellular Ca++, neuronal degeneration and death. 2. Recent in vitro research has demonstrated that a natural cationic amphiphile in the brain, lysosphingomyelin, may be able to prevent neuronal degeneration by repressing phosphosinositidase-C overactivation induced by excessive excitation of the metabotropic glutamate receptor. 3. This research tested the latter finding in vivo in a rat model of glutamate excitotoxicity. Intracerebroventricular (icv) administration of the Group 1 metabotropic glutamate receptor (mGluR) agonist, quisqualate, produced seizures, akinesia, destruction of hippocampal pyramidal cell dendritic microtubule-associated protein-2, and major loss of hippocampal CA sector neurons. 4. Prophylactic icv infusion of lysosphingomyelin powerfully attenuates these quisqualate-induced behaviors and prevents neuronal degeneration. 5. Lysosphingomyelin may be of clinical use in allaying progressive Group 1 mGluR-induced hippocampal cognitive and motor disorders including Alzheimer's disease, brain seizure, and stroke.