Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
Mol Neurobiol. 2018 Feb;55(2):905-916. doi: 10.1007/s12035-017-0381-1. Epub 2017 Jan 12.
Over the last years, many studies reported on the antioxidant effects of ferulic acid (FA) in preclinical models of dementia through the activation of the heme oxygenase/biliverdin reductase (HO/BVR) system. However, only a few studies evaluated whether FA could improve neurological function under milder conditions, such as psychological stress. The aim of this study was to investigate the effects of FA (150 mg/kg intraperitoneal route) on cognitive function in male Wistar rats exposed to emotional arousal. Animals were randomly assigned to two experimental groups, namely not habituated or habituated to the experimental context, and the novel object recognition test was used to evaluate their cognitive performance. The administration of FA significantly increased long-term retention memory in not habituated rats. Ferulic acid increased the expression of HO-1 in the hippocampus and frontal cortex of not habituated rats only, whereas HO-2 resulted differently modulated in these cognitive brain areas. No significant effects on either HO-1 or HO-2 or BVR were observed in the cerebellum of both habituated and not habituated rats. Ferulic acid activated the stress axis in not habituated rats, as shown by the increase in hypothalamic corticotrophin-releasing hormone levels. Pre-treatment with Sn-protoporphyrin-IX [0.25 μmol/kg, intracerebroventricular route (i.c.v.)], a well-known inhibitor of HO activity through which carbon monoxide (CO) and biliverdin (BV) are generated, abolished the FA-induced improvement of cognitive performance only in not habituated rats, suggesting a role for HO-derived by-products. The CO-donor tricarbonyldichlororuthenium (II) (30 nmol/kg i.c.v.) mimicked the FA-related improvement of cognitive skills only in not habituated rats, whereas BV did not have any effect in any group. In conclusion, these results set the stage for subsequent studies on the neuropharmacological action of FA under conditions of psychological stress.
在过去的几年中，许多研究报告了阿魏酸（FA）通过激活血红素加氧酶/胆红素还原酶（HO/BVR）系统在痴呆的临床前模型中的抗氧化作用。然而，只有少数研究评估了 FA 是否可以在轻度条件下改善神经功能，例如心理应激。本研究旨在研究 FA（150mg/kg 腹腔途径）对暴露于情绪唤醒的雄性 Wistar 大鼠认知功能的影响。动物被随机分配到两个实验组，即未适应或适应实验环境，并用新物体识别测试来评估它们的认知表现。FA 的给药显著增加了未适应大鼠的长期保留记忆。FA 仅在未适应大鼠的海马体和前额叶皮层中增加 HO-1 的表达，而 HO-2 在这些认知脑区的表达则不同。在适应和未适应大鼠的小脑，均未观察到 HO-1 或 HO-2 或 BVR 有明显变化。在未适应大鼠中，FA 激活了应激轴，表现为下丘脑促肾上腺皮质激素释放激素水平的增加。用 Sn-原卟啉-IX [0.25μmol/kg，脑室内（i.c.v.）]预处理，这是一种通过生成一氧化碳（CO）和胆红素（BV）来抑制 HO 活性的众所周知的抑制剂，仅在未适应大鼠中消除了 FA 诱导的认知表现的改善，表明 HO 衍生的副产物起作用。CO 供体三羰二氯钌（II）（30nmol/kg i.c.v.）仅在未适应大鼠中模拟了 FA 相关的认知技能改善，而 BV 在任何组中均无作用。总之，这些结果为随后在心理应激条件下进行 FA 的神经药理学作用研究奠定了基础。
