Structural involvement of the glutamatergic presynaptic boutons in a transgenic mouse model expressing early onset amyloid pathology
Structural involvement of the glutamatergic presynaptic boutons in a transgenic mouse model expressing early onset amyloid pathology
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DOI：
10.1016/j.neulet.2003.09.027
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发表时间：
2003-12-19
影响因子：
2.5
通讯作者：
Cuello, AC
中科院分区：
文献类型：
--
作者：
Bell, KFS;de Kort, GJL;Cuello, AC
虽然人们已经知道阿尔茨海默病（AD）的胆碱能耗竭有一段时间了，但其他神经递质系统的明确参与却有些难以捉摸。我们的研究表明，在ad样淀粉样蛋白病理的早期发病转基因小鼠模型中，谷氨酸能神经元和gaba能神经元在较小程度上明显参与。免疫组织化学染色和随后的定量显示，与非转基因对照组相比，转基因小鼠无斑块和斑块邻近皮质神经堆区域的谷氨酸能和氨基丁酸能突触前钮扣密度显著增加。此外，淀粉样斑块的大小对斑块周围神经堆中营养不良的谷氨酸能神经突所占的相对面积有统计学上显著的影响。这些发现支持了我们的假设，即淀粉样蛋白病理以一种特定的时间和神经递质方式发展，首先在胆碱能系统中，这似乎是最脆弱的，其次是谷氨酸能突触前按钮，最后是更有弹性的gaba能终端。2003爱思唯尔爱尔兰有限公司版权所有。
While the cholinergic depletion in Alzheimer's disease (AD) has been known for some time, a definitive involvement of other neurotransmitter systems has been somewhat more elusive. Our study demonstrates a clear involvement of both glutamatergic and, to a lesser extent, GABAergic neurons in an early onset transgenic mouse model of AD-like amyloid pathology. Immunohistochemical staining and subsequent quantification has revealed a statistically significant increased density of glutamatergic and GABAergic presynaptic boutons in both the plaque free and plaque adjacent cortical neuropile areas of transgenic mice as compared to non-transgenic controls. Furthermore, amyloid plaque size was shown to have a statistically significant effect on the relative area occupied by dystrophic glutamatergic neurites in the peri-plaque neuropile. These findings support our hypothesis that the amyloid pathology progresses in a time and neurotransmitter specific manner, first in the cholinergic system which appears to be most vulnerable, followed by the glutamatergic presynaptic boutons and finally the somewhat more resilient GABAergic terminals. (C) 2003 Elsevier Ireland Ltd. All rights reserved.