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 和尼古丁N-甲基-D-天冬氨酸（NMDA）神经毒性是一种模型， 反映了人类疾病的关键方面。 NMDA 激活一种谷氨酸受体亚型， 钙 钙的流入会导致，除其他影响外， 鸟氨酸脱羧酶（ODC）的激活，第一和速率- 多胺合成的限制酶。 假设作为一个 结果增加生物合成的精胺，NMDA受体 被进一步激活，更多的钙进入细胞质， 一个致命的恶性循环 不可逆的ODC抑制剂α- 二氟甲基鸟氨酸（DFMO）防止NMDA神经毒性， 据说是因为它能降低精胺水平 然而，聚胺- DFMO的消耗活性低并且由于复杂的规则， 它实际上增加了大脑皮层中精胺的浓度。 DFMO神经保护活性的另一种解释是 在这里提出。 DFMO是海马切片中的一种温和兴奋剂，因为 是另一种神经保护剂尼古丁 这种温和的， 特异性刺激增加神经营养素的合成， 促进神经元存活。 海马脑片和皮层细胞 培养物将用于测试上述模型的预测， 其中一些是：DFMO在存在的情况下具有神经保护作用 外源腐胺，非刺激性的ODC抑制剂将不会 具有神经保护作用，DFMO和尼古丁都能增加 神经营养因子，DFMO和尼古丁都不是神经保护性的， 存在抗神经营养因子的抗体。 这一工作将有助于阐明ODC和多胺的作用 在神经毒性和文本中， 不同化合物如DFMO和 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.