Combined Bazedoxifene and Genistein Ameliorate Ovariectomy-Induced Hippocampal Neuro-Alterations via Activating CREB/BDNF/TrkB Signaling Pathway.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current molecular pharmacology Pub Date : 2023-01-01 DOI:10.2174/1874467215666220902112939

Mai A Samak, Abeer A Abdelrahman, Walaa Samy, Shaimaa A Abdelrahman

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引用次数: 0

Abstract

Objectives: The scientific research community devotes stupendous efforts to control the arguable counterbalance between the undesirable effects of hormone replacement therapy (HRT) and post-menopausal syndrome. The recent emergence of 3rd generation selective estrogen receptor modulators and phytoestrogens has provided a promising alternative to HRT. Hence, we assessed the potential effects of combined Bazedoxifene and Genistein on hippocampal neuro-alterations induced by experimental ovariectomy.

Methods: For this purpose, we utilized forty-eight healthy sexually mature female Wistar rats assorted to control, ovariectomy (OVX), Genistein-treated ovariectomized (OVX+GEN) and Bazedoxifene and Genistein-treated ovariectomized (OVX+BZA+GEN) groups. Hippocampi samples from various groups were examined by H&E, silver stains and immunohistochemical examination for calbindin-D28k, GFAP, and BAX proteins. We also assessed hippocampal mRNA expression of ERK, CREB, BDNF and TrkB.

Results: Our histopathological results confirmed that combined BZA+GEN induced restoration of hippocampal neuronal architecture, significant reduction of GFAP and BAX mean area % and significant upregulation of calbindin-D28k immunoexpression. Furthermore, we observed significant upregulation of ERK, CREB, BDNF and TrkB mRNA expression in the BZA+GEN group compared to the OVX group.

Conclusion: Taken together, our findings have provided a comprehensive assessment of histological, immunohistochemical and cyto-molecular basis of combined Genistein and Bazedoxifene ameliorative impacts on hippocampal neuro-alterations of OVX rats via upregulation of Calbindin, CERB, BDNF, Trk-B and ERK neuronal expression.

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通过激活CREB/BDNF/TrkB信号通路，联合使用巴泽多昔芬和染料木素改善卵巢切除术诱导的海马神经改变。

目的:科学研究界投入了巨大的努力来控制激素替代疗法(HRT)和绝经后综合征之间的不良影响之间有争议的平衡。最近出现的第三代选择性雌激素受体调节剂和植物雌激素为HRT提供了一个有希望的替代方案。因此，我们评估了联合使用巴泽多昔芬和染料木黄酮对实验性卵巢切除术诱导的海马神经改变的潜在影响。方法:选用健康性成熟雌性Wistar大鼠48只，分为对照组、卵巢切除组(OVX)、染料木黄酮组(OVX+GEN)和巴泽多昔芬组(OVX+BZA+GEN)。各组海马标本采用H&E、银染色和免疫组化检测calbinin - d28k、GFAP和BAX蛋白。我们还评估了海马ERK、CREB、BDNF和TrkB的mRNA表达。结果:我们的组织病理学结果证实，BZA+GEN联合用药诱导海马神经元结构恢复，GFAP和BAX平均面积%显著降低，calbinin - d28k免疫表达显著上调。此外，我们观察到与OVX组相比，BZA+GEN组的ERK、CREB、BDNF和TrkB mRNA表达显著上调。结论:综上所述，我们的研究结果提供了一个全面的组织学、免疫组织化学和细胞分子基础的评估，染料木素和巴齐多昔芬联合治疗通过上调Calbindin、CERB、BDNF、Trk-B和ERK神经元的表达来改善OVX大鼠海马神经的改变。

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

Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

4.90

自引率

3.70%

发文量

112

期刊介绍： Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.