University of Wisconsin-Whitewater, Janesville, Wisconsin 53546.
Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon 97331.
eNeuro. 2019 Feb 7;6(1). doi: 10.1523/ENEURO.0310-18.2019. eCollection 2019 Jan-Feb.
Cognitive decline with aging is often due to altered levels of protein expression. The NMDA receptor (NMDAR) and the complex of proteins surrounding the receptor are susceptible to age-related changes in expression. In the frontal cortex of aged mice, there is a significant loss of expression of the GluN2B subunit of the NMDAR, an increase in Fyn expression, and no change in PSD-95. Studies have also found that, in the frontal cortex, phosphorylation of GluN2B subunits and palmitoylation of GluN2 subunits and NMDAR complex proteins are affected by age. In this study, we examined some of the factors that may lead to the differences in the palmitoylation levels of NMDAR complex proteins in the frontal cortex of aged animals. The Morris water maze was used to test spatial learning in 3- and 24-month-old mice. The acyl-biotinyl exchange method was used to precipitate palmitoylated proteins from the frontal cortices and hippocampi of the mice. Additionally, brain lysates from old and young mice were probed for the expression of fatty acid transporter proteins. An age-related increase of palmitoylated GluN2A, GluN2B, Fyn, PSD-95, and APT1 (acyl protein thioesterase 1) in the frontal cortex was associated with poorer reference memory and/or executive functions. These data suggest that there may be a perturbation in the palmitoylation cycle in the frontal cortex of aged mice that contributes to age-related cognitive declines.
随着年龄的增长，认知能力下降通常是由于蛋白质表达水平的改变。NMDA 受体（NMDAR）及其受体周围的蛋白质复合物容易受到与年龄相关的表达变化的影响。在老年小鼠的前额皮质中，NMDAR 的 GluN2B 亚基表达显著减少，Fyn 表达增加，而 PSD-95 没有变化。研究还发现，在前额皮质中，GluN2B 亚基的磷酸化和 GluN2 亚基和 NMDAR 复合物蛋白的棕榈酰化受到年龄的影响。在这项研究中，我们研究了一些可能导致老年动物前额皮质中 NMDAR 复合物蛋白棕榈酰化水平差异的因素。使用 Morris 水迷宫测试 3 个月和 24 个月大的小鼠的空间学习能力。酰基辅酶 A-生物素交换法从小鼠的前额皮质和海马沉淀棕榈酰化蛋白。此外，还检测了老年和年轻小鼠大脑裂解物中脂肪酸转运蛋白的表达。与参考记忆和/或执行功能较差相关的是，前额皮质中与年龄相关的棕榈酰化 GluN2A、GluN2B、Fyn、PSD-95 和 APT1（酰基蛋白硫酯酶 1）增加。这些数据表明，老年小鼠前额皮质中可能存在棕榈酰化循环的紊乱，这可能导致与年龄相关的认知能力下降。
