Aβ (1-42) 肽诱导的阿尔茨海默病大鼠模型中红豆杉素的神经保护作用

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-08-21 DOI:10.1016/j.neuint.2024.105839
Wasi Uzzaman Khan , Mohd Salman , Mubashshir Ali , Haya Majid , M Shahar Yar , Mohd Akhtar , Suhel Parvez , Abul Kalam Najmi
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引用次数: 0

摘要

阿尔茨海默病(AD)的病因错综复杂,给有效干预措施的开发带来了巨大障碍。绿萘素(SFN)因其抗氧化、抗炎和神经保护特性而备受关注,它可以解决阿尔茨海默病病理的各个方面。本研究探讨了SFN在Aβ(1-42)肽诱导的AD大鼠模型中的潜力。向大鼠脑室直接注射Aβ(1-42)肽,诱发大鼠出现AD症状。给Aβ(1-42)治疗动物注射SFN(10毫克/千克和20毫克/千克)、曲戈奈林(10毫克/千克)和吡格列酮(10毫克/千克)。行为评估采用新物体识别测试。使用酶联免疫吸附试剂盒和分光光度法对各种生化指标进行量化,如可溶性 Aβ (1-42)、IRS-S312、GSK-3β、TNF-α、乙酰胆碱酯酶、亚硝酸盐水平、脂质过氧化和还原型谷胱甘肽活性。组织病理学分析包括苏木精和伊红、刚果红和 IRS-1 免疫组织化学染色。对神经元损失和Aβ斑块负担进行量化评估。这项研究的新颖之处在于它以双重剂量全面评估了SFN对多种AD相关通路的影响。新物体识别测试显示,SFN,尤其是高剂量的SFN,可改善Aβ(1-42)诱导的记忆缺陷。在生化方面,SFN能降低海马Aβ水平、IRS-S312、GSK-3β、TNF-α和乙酰胆碱酯酶活性,同时提高谷胱甘肽水平,所有这些均呈剂量依赖性。组织病理学分析进一步证实了 SFN 对 Aβ 诱导的神经元损伤、淀粉样变性和胰岛素信号变化的保护作用。这些结果凸显了SFN作为一种多方面的AD治疗剂的潜力,它的抗氧化、抗炎和神经保护特性为治疗提供了一种前景广阔的途径。在使用SFN的同时使用曲高奈林和吡格列酮进行联合治疗,有助于深入了解潜在的协同效应,从而为开发AD联合疗法铺平道路。
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Neuroprotective Effects of Sulforaphane in a rat model of Alzheimer's Disease induced by Aβ (1–42) peptides

The intricate nature of Alzheimer's disease (AD) has presented significant hurdles in the development of effective interventions. Sulforaphane (SFN) is of interest due to its antioxidative, anti-inflammatory, and neuroprotective properties, which could address various aspects of AD pathology. This study explores the potential of SFN in a rat model of AD induced by Aβ (1–42) peptides. AD symptoms were triggered in rats by injecting Aβ (1–42) peptides directly into their cerebral ventricles. SFN (10 mg/kg and 20 mg/kg), Trigonelline (10 mg/kg), and Pioglitazone (10 mg/kg) were administered in Aβ (1–42) treated animals. Behavioral assessments were performed using the Novel Object Recognition tests. Various biochemical parameters, such as soluble Aβ (1–42), IRS-S312, GSK-3β, TNF-α, acetylcholinesterase, nitrite levels, lipid peroxidation, and reduced glutathione activity, were quantified using ELISA kits and spectrophotometric assays. Histopathological analyses included Hematoxylin and Eosin, Crystal Violet, Congo red, and IRS-1 Immunohistochemistry staining. Quantification was performed to assess neuronal loss and Aβ plaque burden. The novelty of this study lies in its comprehensive evaluation of SFN's impact on multiple AD-related pathways at dual doses. The Novel Object Recognition test revealed that SFN, especially at higher doses, improved memory deficits induced by Aβ (1–42). Biochemically, SFN reduced hippocampal Aβ levels, IRS-S312, GSK-3β, TNF-α, and acetylcholinesterase activity, while increasing glutathione levels, all in a dose-dependent manner. Histopathological analyses further confirmed SFN's protective role against Aβ-induced neuronal damage, amyloidosis, and changes in insulin signaling. These results highlight SFN's potential as a multifaceted therapeutic agent for AD, offering a promising avenue for treatment due to its antioxidative, anti-inflammatory, and neuroprotective properties. The inclusion of combination treatments with Trigonelline and Pioglitazone alongside SFN offers insights into potential synergistic effects, which could pave the way for developing combination therapies for AD.

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来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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