Ferulic acid ameliorates bisphenol A (BPA)-induced Alzheimer's disease-like pathology through Akt-ERK crosstalk pathway in male rats.

IF 3.5 3区医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2024-10-23 DOI:10.1007/s00213-024-06697-4

Mhasen Khalifa, Rabie H Fayed, Yasmine H Ahmed, Mohamed F Abdelhameed, Ahmed F Essa, Heba M A Khalil

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Abstract

Objectives: This study investigated the neuroprotective effect of ferulic acid (FA) against bisphenol A (BPA) induced Alzheimer's disease-like pathology in male rats.

Methods: Rats were allocated into four groups, control, BPA, BPA + FA, and FA, respectively, for 40 days. Spatial working memory and recognition memory were evaluated. Moreover, the brain levels of oxidative stress biomarkers, proinflammatory cytokines, extracellular signal-regulated kinase (ERK), and phosphorylated serine/threonine protein kinase (p-Akt) were measured. We also determined the brain neuropathological protein levels, including Beta-Amyloid 1-42, total Tau (tTau), and phosphorylated Tau (pTau) proteins. Furthermore, brain levels of Acetylcholinesterase (AChE) and Beta-secretase (BACE) were assessed. Brain histological investigation and immunohistochemistry determination of glial fibrillar acidic protein (GFAP) were also performed. Moreover, docking simulation was adapted to understand the inhibitory role of FA on AChE, BACE-1, and ERK1/2.

Results: Interestingly, the BPA + FA treated group showed a reversal in the cognitive impairments induced by BPA, which was associated with improved brain redox status. They also exhibited a significant decrease in brain inflammatory cytokines, ERK, and p-Akt levels. Moreover, they revealed a decline in beta-amyloid 1-42 and a significant improvement in tTau expression and pTau protein levels in the brain tissue. Further, the brain levels of AChE and BACE were substantially reduced in BPA + FA rats. The neuroprotective effect of FA was confirmed by restoring the normal architecture of brain tissue, which was associated with decreasing GFAP.

Conclusion: FA could be a potent neuroprotectant agent against AD with a possible prospect for its therapeutic capabilities and nutritional supplement value due to its antioxidant and antiapoptotic properties.

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阿魏酸通过Akt-ERK串联通路改善雄性大鼠双酚A（BPA）诱导的阿尔茨海默病样病理变化

研究目的本研究探讨了阿魏酸（FA）对双酚 A（BPA）诱导的雄性大鼠阿尔茨海默病样病理变化的神经保护作用：方法：将大鼠分为对照组、双酚 A 组、双酚 A + 阿魏酸组和阿魏酸组四组，分别饲养 40 天。评估大鼠的空间工作记忆和识别记忆。此外，还测定了脑氧化应激生物标志物、促炎细胞因子、细胞外信号调节激酶（ERK）和磷酸化丝氨酸/苏氨酸蛋白激酶（p-Akt）的水平。我们还测定了脑神经病理蛋白水平，包括β-淀粉样蛋白1-42、总Tau（tTau）和磷酸化Tau（pTau）蛋白。此外，还评估了大脑乙酰胆碱酯酶（AChE）和β-分泌酶（BACE）的水平。还进行了脑组织学调查和神经胶质纤维酸性蛋白（GFAP）的免疫组化测定。此外，还进行了对接模拟，以了解 FA 对 AChE、BACE-1 和 ERK1/2 的抑制作用：有趣的是：双酚A+FA治疗组逆转了双酚A引起的认知障碍，这与大脑氧化还原状态的改善有关。他们还表现出脑炎症细胞因子、ERK 和 p-Akt 水平的显著下降。此外，他们还发现脑组织中的β-淀粉样蛋白1-42有所下降，tTau表达和pTau蛋白水平显著改善。此外，双酚 A + FA 大鼠脑中 AChE 和 BACE 的水平也大幅降低。脑组织正常结构的恢复证实了 FA 的神经保护作用，这与 GFAP 的降低有关：结论：由于 FA 具有抗氧化和抗细胞凋亡的特性，它可能是一种有效的神经保护剂，具有治疗功能和营养补充剂的价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.