N-methyl-D-aspartate receptor antagonists have variable affect in 3-nitropropionic acid toxicity.
N-methyl-D-aspartate receptor antagonists have variable affect in 3-nitropropionic acid toxicity.
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DOI：
10.1007/s11064-008-9809-3
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发表时间：
2009-03
影响因子：
4.4
通讯作者：
Geddes, James W.
中科院分区：
文献类型：
--
作者：
Nasr, Payman;Carbery, Timothy;Geddes, James W.
关键词：
越来越多的证据表明，谷氨酸（N-甲基-d-天冬氨酸）NMDA受体过度激活引起的兴奋性毒性和氧化应激是与3-硝基丙酸（3 NP）给药相关的纹状体变性的主要参与者。尽管兴奋性毒性和氧化机制与3 NP毒性有关，但关于NMDA受体拮抗剂是否减弱或加剧3 NP诱导的神经变性的报道相互矛盾。在本研究中，我们调查了NMDA受体参与纹状体变性，蛋白质氧化和运动障碍后，系统的3 NP管理。我们研究了NMDA受体拮抗剂美金刚和艾芬地尔是否影响3 NP的神经毒性。美金刚可延缓3 NP给药后纹状体损伤和蛋白质氧化的发展，但不受艾芬地尔的影响。然而，在行为实验中，美金刚胺未能改善，艾芬地尔加剧了与3 NP毒性相关的运动缺陷。总之，这些发现提示在与代谢损伤相关的神经退行性疾病中应用NMDA受体拮抗剂作为神经保护剂时应谨慎。
There is accumulating evidence that excitotoxicity and oxidative stress resulting from excessive activation of glutamate (N-methyl-d-aspartate) NMDA receptors are major participants in striatal degeneration associated with 3-nitropropionic acid (3NP) administration. Although excitotoxic and oxidative mechanisms are implicated in 3NP toxicity, there are conflicting reports as to whether NMDA receptor antagonists attenuate or exacerbate the 3NP-induced neurodegeneration. In the present study, we investigated the involvement of NMDA receptors in striatal degeneration, protein oxidation and motor impairment following systemic 3NP administration. We examined whether NMDA receptor antagonists, memantine and ifenprodil, influence the neurotoxicity of 3NP. The development of striatal lesion and protein oxidation following 3NP administration is delayed by memantine but not affected by ifenprodil. However, in behavioral experiments, memantine failed to improve and ifenprodil exacerbated the motor deficits associated with 3NP toxicity. Together, these findings suggest caution in the application of NMDA receptor antagonists as a neuroprotective agent in neurodegenerative disorders associated with metabolic impairment.
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DOI：
10.1016/s1385-299x(96)00037-2
发表时间：
1997-08-01
期刊：
BRAIN RESEARCH PROTOCOLS
影响因子：
--
作者：
Borlongan, CV;Koutouzis, TK;Sanberg, PR
通讯作者：
Sanberg, PR
影响因子：
1.7
作者：
BEHRENS, MI;KOH, J;CHOI, DW
通讯作者：
CHOI, DW
影响因子：
64.8
作者：
BEKKERS, JM;STEVENS, CF
通讯作者：
STEVENS, CF
影响因子：
2.5
作者：
Blanpied, TA;Boeckman, FA;Johnson, JW
通讯作者：
Johnson, JW
影响因子：
5.3
作者：
Calabresi, P;Gubellini, P;Bernardi, G
通讯作者：
Bernardi, G