Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain
Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain
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DOI：
10.1038/srep26199
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发表时间：
2016-05-27
影响因子：
4.6
通讯作者：
Dickstein, Dara L.
中科院分区：
文献类型：
--
作者：
Lazarczyk, Maciej J.;Kemmler, Julia E.;Dickstein, Dara L.
主要组织相容性复合物I类（MHCI）蛋白质已经通过调节发育期间的神经突发生、突触发生、突触可塑性和记忆巩固而涉及神经元功能。然而，MHCI在老年大脑中的参与尚不清楚。在这里，我们证明，MHCI缺乏导致显着的树突萎缩沿着增加，在薄的树突棘和减少在老年（12个月大）小鼠海马中的树突棘。超微结构分析显示，减少了棘头直径和突触后密度（PSD）的面积，以及增加整体突触密度，和非穿孔，小棘。有趣的是，我们发现突触密度和形态的变化出现相对较晚（6个月后）。最后，我们发现一个显着的年龄依赖性增加的谷氨酸受体，GluN 2B在老年MHCI基因敲除小鼠的水平，在GluA 2/3，VGluT 1，PSD 95或突触素没有变化。这些结果表明，MHCI也可能参与在发育后阶段维持脑的完整性，特别是在非病理性衰老过程中神经元和脊柱形态和突触功能的调节，这可能对认知功能具有重要意义。
Major histocompatibility complex class I (MHCI) proteins have been implicated in neuronal function through the modulation of neuritogenesis, synaptogenesis, synaptic plasticity, and memory consolidation during development. However, the involvement of MHCI in the aged brain is unclear. Here we demonstrate that MHCI deficiency results in significant dendritic atrophy along with an increase in thin dendritic spines and a reduction in stubby spines in the hippocampus of aged (12 month old) mice. Ultrastructural analyses revealed a decrease in spine head diameter and post synaptic density (PSD) area, as well as an increase in overall synapse density, and non-perforated, small spines. Interestingly, we found that the changes in synapse density and morphology appear relatively late (after the age of 6 months). Finally, we found a significant age dependent increase in the levels of the glutamate receptor, GluN2B in aged MHCI knockout mice, with no change in GluA2/3, VGluT1, PSD95 or synaptophysin. These results indicate that MHCI may be also be involved in maintaining brain integrity at post-developmental stages notably in the modulation of neuronal and spine morphology and synaptic function during non-pathological aging which could have significant implications for cognitive function.