A selective role for ARMS/Kidins220 scaffold protein in spatial memory and trophic support of entorhinal and frontal cortical neurons
A selective role for ARMS/Kidins220 scaffold protein in spatial memory and trophic support of entorhinal and frontal cortical neurons
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DOI：
10.1016/j.expneurol.2011.03.008
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发表时间：
2011-06-01
影响因子：
5.3
通讯作者：
Scharfman, Helen E.
中科院分区：
文献类型：
--
作者：
Duffy, Aine M.;Schaner, Michael J.;Scharfman, Helen E.
进行性皮层病理是常见的一些神经退行性和精神疾病。内嗅皮层（EC）和额叶皮层（FC）特别脆弱，神经营养因子被认为是有保护作用的。作为神经营养因子的下游信号传感器，富含锚蛋白重复的跨膜支架蛋白/Kidins 220 （ARMS）在皮层中表达，在营养支持中发挥重要作用。为了验证这一假设，我们评估了ARMS杂合缺失的小鼠（ARMS小鼠）。值得注意的是，EC和FC是表现出最大缺陷的区域。在ARMS（+/-）小鼠中，许多EC和FC神经元发生固缩，因此在12月龄时，EC和FC的大面积受到影响。ARMS（+/-）小鼠EC和FC的固缩区也表现为对神经元抗原的免疫反应性丧失。NeuN，在皮层神经元损伤后被报道。电镜观察显示，ARMS（+/-）小鼠EC和FC的线粒体、髓鞘和多层体存在缺陷。虽然主要局限于EC和FC，但病理学似乎足以引起功能损伤，因为ARMS（+/-）小鼠在Morris水迷宫中的表现比野生型更差。雄性和雌性的比较表明，雌性小鼠在所有的比较中都是受影响的性别。综上所述，结果表明，一个突出的神经营养受体底物的表达通常保护EC和FC，而ARMS可能在女性中特别重要。Elsevier Inc.出版。
Progressive cortical pathology is common to several neurodegenerative and psychiatric disorders. The entorhinal cortex (EC) and frontal cortex (FC) are particularly vulnerable, and neurotrophins have been implicated because they appear to be protective. A downstream signal transducer of neurotrophins, the ankyrin repeat-rich membrane spanning scaffold protein/Kidins 220 (ARMS) is expressed in the cortex, where it could play an important role in trophic support. To test this hypothesis, we evaluated mice with a heterozygous deletion of ARMS (ARMS' mice). Remarkably, the EC and FC were the regions that demonstrated the greatest defects. Many EC and FC neurons became pyknotic in ARMS(+/-) mice, so that large areas of the EC and FC were affected by 12 months of age. Areas with pyknosis in the EC and FC of ARMS(+/-) mice were also characterized by a loss of immunoreactivity to a neuronal antigen. NeuN, which has been reported after insult or injury to cortical neurons. Electron microscopy showed that there were defects in mitochondria, myelination, and multilamellar bodies in the EC and FC of ARMS(+/-) mice. Although primarily restricted to the EC and FC, pathology appeared to be sufficient to cause functional impairments, because ARMS(+/-) mice performed worse than wild-type on the Morris water maze. Comparisons of males and females showed that female mice were the affected sex in all comparisons. Taken together, the results suggest that the expression of a prominent neurotrophin receptor substrate normally protects the EC and FC, and that ARMS may be particularly important in females. Published by Elsevier Inc.