NEUROPROTECTION FROM NMDA TOXICITY BY ALPHA DIFLUOROMETHYLORNITHINE AND NICOTINE

α-二氟甲基鸟氨酸对NMDA毒性的神经保护作用 而尼古丁N-甲基-D-天冬氨酸(NMDA)的神经毒性是 反映人类疾病的关键方面的中风。NMDA 激活谷氨酸受体的一种亚型，这种受体可能会 钙。钙的流入除了其他影响外，还会引起 鸟氨酸脱羧酶(ODC)活性的第一和速率- 多胺合成的限制酶。假设作为一个 NMDA受体精胺生物合成增加的结果 进一步激活，更多的钙进入细胞质，导致 一个致命的恶性循环。不可逆ODC抑制剂α- 二氟甲基鸟氨酸(DFMO)可预防NMDA神经毒性， 据说是因为它降低了精胺水平。然而，多胺- DFMO的消耗活性较低，而且由于复杂的法规， 它实际上会增加大脑皮层中的精胺浓度。 DFMO神经保护活性的另一种解释是 在这里求婚。DFMO是海马片中的一种温和的刺激剂，因为 是另一种神经保护剂尼古丁。这是温和的和 特定的刺激增加了神经营养因子的合成， 促进神经元存活。海马片和皮质细胞 文化将被用来检验上述模型的预测， 其中一些是：DFMO在存在的情况下具有神经保护作用 外源性腐胺、非刺激性的ODC抑制剂不会 具有神经保护作用，DFMO和尼古丁都会增加 神经营养素，无论是DFMO还是尼古丁，都不具有神经保护作用。 神经营养素抗体的存在。 这项工作将有助于阐明ODC和多胺的作用 在神经毒性和文本中，一个假设整合了 DFMO和DFMO等不同化合物的神经保护作用 尼古丁。

Neuroprotection from NMDA toxicity by alpha-difluromethylornithine and nicotine N-methyl-D-aspartate (NMDA) neurotoxicity is a model of stroke that reflects critical aspects of the human disease. NMDA activates a subtype of glutamate receptors that is permeant to calcium. The influx of calcium causes, among other effects, activation of ornithine decarboxylase (ODC), the first and rate- limiting enzyme of polyamine synthesis. It is assumed that as a result of the increased biosynthesis of spermine, the NMDA receptor is further activated and more calcium enter the cytoplasm leading to a deadly vicious cycle. The irreversible ODC inhibitor alpha- difluoromethylornithine (DFMO) prevents NMDA neurotoxicity, supposedly because it lowers spermine level. However, the polyamine- depleting activity of DFMO is low and because of complex regulations, it actually increases spermine concentration in cerebral cortex. An alternative explanation for DFMO neuroprotective activity is proposed here. DFMO is a mild stimulant in the hippocampal slice, as is another neuroprotective agent, nicotine. This moderate and specific stimulation increases the synthesis of neurotrophins, which promote neuronal survival. Hippocampal slices and cortical cell cultures will be used to test the predictions of the above model, some of which are: DFMO is neuroprotective in the presence of exogenous putrescine, ODC inhibitors that are not stimulant will not be neuroprotective, both DFMO and nicotine increase the level of neurotrophins, neither DFMO nor nicotine are neuroprotective in the presence of antibodies against neuroptrophins. This work will contribute to clarify the role of ODC and polyamines in neurotoxicity and text a hypothesis that integrates neuroprotective effects of dissimilar compounds like DFMO and nicotine.