Morin Jean-Pascal, Díaz-Cintra Sofía, Bermúdez-Rattoni Federico, Delint-Ramírez Ilse
Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Mexico; Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Unidad Lerma, Mexico.
Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Mexico.
Neurochem Int. 2016 Nov;100:159-163. doi: 10.1016/j.neuint.2016.09.013. Epub 2016 Sep 17.
It was recently suggested that alteration in lipid raft composition in Alzheimer's disease may lead to perturbations in neurons signalosome, which may help explain the deficits observed in synaptic plasticity mechanisms and long-term memory impairments in AD models. As a first effort to address this issue, we evaluated lipid-raft contents of distinct NMDA and AMPA receptor subunits in the hippocampus of the 3xTg-AD model of Alzheimer's disease. Our results show that compared to controls, 10 months-old 3xTg-AD mice have diminished levels of NMDA receptors in rafts but not in post-synaptic density or total fractions. Additionally, the levels of GluR1 were unaltered in all the analyzed fractions. Finally, we went on to show that the diminished levels of NMDA receptors in rafts correlated with diminished global levels of Arc/Arg3.1, a synaptic protein with a central role in long-term memory formation. This study adds to our current understanding of the signaling pathways disruptions observed in current Alzheimer's disease models.
最近有研究表明，阿尔茨海默病中脂筏成分的改变可能导致神经元信号体的紊乱，这或许有助于解释在阿尔茨海默病模型中观察到的突触可塑性机制缺陷和长期记忆损伤。作为解决这一问题的初步尝试，我们评估了阿尔茨海默病3xTg-AD模型海马体中不同NMDA和AMPA受体亚基的脂筏含量。我们的结果显示，与对照组相比，10月龄的3xTg-AD小鼠脂筏中NMDA受体水平降低，但突触后致密物或总组分中的水平未降低。此外，在所有分析组分中，GluR1的水平未发生改变。最后，我们进一步表明，脂筏中NMDA受体水平的降低与Arc/Arg3.1的整体水平降低相关，Arc/Arg3.1是一种在长期记忆形成中起核心作用的突触蛋白。这项研究增进了我们目前对当前阿尔茨海默病模型中观察到的信号通路破坏的理解。
