The neurotoxin 2'-NH2-MPTP degenerates serotonin axons and evokes increases in hippocampal BDNF.
The neurotoxin 2'-NH2-MPTP degenerates serotonin axons and evokes increases in hippocampal BDNF.
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神经毒素 2-NH2-MPTP 使血清素轴突退化并引起海马 BDNF 增加。
DOI：
10.1016/j.neuropharm.2005.09.006
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Andrews,AnneM
中科院分区：
文献类型：
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作者：
Luellen,BethA;Szapacs,MatthewE;Materese,ChristopherK;Andrews,AnneM
1-甲基-4-（2′-氨基苯基）-1，2，3，6-四氢吡啶（2′-NH 2-MPTP）可引起皮质和海马5-羟色胺（5-HT）和去甲肾上腺素（NE）的长期耗竭，并伴有胶质细胞酸性蛋白（GFAP）和嗜银蛋白的急性升高。为了进一步研究这些变化反映了肾上腺素能和去甲肾上腺素能轴突变性的假设，将2′-NH 2-MPTP给予小鼠，并用免疫细胞化学方法测定神经支配密度。区域反应的神经营养因子，脑源性神经营养因子（BDNF），推定的损害也进行了评估。2′-NH 2-MPTP后3天，5-HT轴突呈现串珠状、扭曲的外观，表明正在进行的变性。在21天，5-羟色胺轴突的数量显着减少，最大的轴突损失发生在皮层和海马。杏仁核中的5-羟色胺轴突与脑干中的5-HT和NE细胞体相比，没有受到长期损伤。BDNF蛋白水平在给药后3天在海马中选择性增加，并在21天后恢复正常。这些结果与以前的研究结果相结合，表明2′-NH 2-MPTP导致支配皮层和海马的多巴胺能轴突变性，并伴有神经递质水平的耗竭。此外，海马体（一个对学习和记忆以及焦虑和应激反应的调节很重要的大脑区域）的损伤会导致BDNF的短暂增加。
1-Methyl-4-(2′-aminophenyl)-1,2,3,6-tetrahydropyridine (2′-NH2-MPTP) causes long-term depletions in cortical and hippocampal serotonin (5-HT) and norepinephrine (NE) that are accompanied by acute elevations in glial fibrillary acidic protein (GFAP) and argyrophilia. To further investigate the hypothesis that these changes are reflective of serotonergic and noradrenergic axonal degeneration, 2′-NH2-MPTP was administered to mice and innervation densities were determined immunocytochemically. Regional responses of the neurotrophin, brain-derived neurotrophic factor (BDNF), to putative damage were also assessed. Three days after 2′-NH2-MPTP, 5-HT axons exhibited a beaded, tortuous appearance indicative of ongoing degeneration. At 21 days, numbers of serotonin axons were significantly decreased, with the greatest axonal losses occurring in cortex and hippocampus. Serotonin axons in the amygdala were contrastingly spared long-term damage, as were 5-HT and NE cell bodies in the brain stem. BDNF protein levels were selectively increased in the hippocampus 3 days post-dose and returned to normal 21 days later. These results, in conjunction with previous findings, demonstrate that 2′-NH2-MPTP causes degeneration of serotonergic axons innervating the cortex and hippocampus on par with depletions in neurotransmitter levels. Moreover, damage to the hippocampus, a brain region important for learning and memory, and the modulation of anxiety and stress responsiveness, results in a transitory increase in BDNF.