Institute for Biological Research, University of Belgrade, Belgrade, Serbia.
Institute for Biological Research, University of Belgrade, Belgrade, Serbia.
Exp Gerontol. 2017 Nov;98:62-69. doi: 10.1016/j.exger.2017.08.010. Epub 2017 Aug 9.
The administration of dexamethasone, a synthetic glucocorticoid receptor agonist, has been reported to modulate cognitive performance in both animals and humans. In the present study, we demonstrate the effects of a single high dose of dexamethasone on the expression and distribution of synaptic plasticity-related proteins, growth-associated protein-43 (GAP-43) and synaptophysin, in the hippocampus of 6-, 12-, 18- and 24-month-old rats. Acute dexamethasone treatment significantly altered the expression of GAP-43 at the posttranslational level by modulating the levels of phosphorylated GAP-43 and proteolytic GAP-43-3 fragment. The effect was the most pronounced in the hippocampi of the aged animals. The total GAP-43 protein was increased only in 24-month-old dexamethasone-treated animals, and was concomitant with a decrease in calpain-mediated proteolysis. Moreover, by introducing the gray level co-occurrence matrix method, a form of texture analysis, we were able to reveal the subtle differences in the expression pattern of both GAP-43 and synaptophysin in the hippocampal subfields that were not detected by Western blot analysis alone. Therefore, the current study demonstrates, through a novel combined approach, that dexamethasone treatment significantly affects both GAP-43 and synaptophysin protein expression in the hippocampus of aged rats.
地塞米松是一种合成的糖皮质激素受体激动剂，有研究报道其可调节动物和人类的认知功能。本研究旨在探讨单次大剂量地塞米松对 6 月龄、12 月龄、18 月龄和 24 月龄大鼠海马突触可塑性相关蛋白生长相关蛋白-43（GAP-43）和突触素表达和分布的影响。急性地塞米松处理通过调节磷酸化 GAP-43 和 GAP-43-3 片段的蛋白水解水平，显著改变了 GAP-43 的翻译后表达。这种作用在老年动物的海马中最为明显。总 GAP-43 蛋白仅在 24 月龄的地塞米松处理组大鼠中增加，同时伴有钙蛋白酶介导的蛋白水解减少。此外，通过引入灰度共生矩阵方法（一种纹理分析方法），我们能够揭示 Western blot 分析单独检测不到的海马亚区中 GAP-43 和突触素表达模式的细微差异。因此，本研究通过一种新的联合方法证明，地塞米松处理显著影响老年大鼠海马中 GAP-43 和突触素蛋白的表达。
