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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

棕榈酰化催乳素释放肽减少小脑 Aβ 斑块和小胶质细胞增生：APP/PS1 小鼠研究

卷 18, 期 8, 2021

发表于: 22 September, 2021

页: [607 - 622] 页: 16

弟呕挨: 10.2174/1567205018666210922110652

价格: $65

摘要

背景：催乳素释放肽 (PrRP) 是一种潜在的治疗肥胖症和相关 2 型糖尿病 (T2DM) 的药物，因为它具有很强的厌食和抗糖尿病特性。在我们最近的研究中，脂质化 PrRP 类似物 palm11-PrRP31 被证明对 APP/PS1 小鼠产生有益作用，这是一种阿尔茨海默病 (AD) 样淀粉样蛋白-β (Aβ) 病理学模型，可减少 Aβ 斑块负荷，海马和皮层的小胶质细胞增生和星形胶质细胞增生。 目的：在这项研究中，我们专注于 palm11-PrRP31 的神经保护和抗炎作用及其对 APP/PS1 小鼠小脑突触发生的可能影响，因为其他人认为小脑 Aβ 斑块会导致 AD 认知缺陷。 方法：与对照小鼠相比，APP/PS1 小鼠用 palm11-PrRP31 皮下治疗 2 个月，然后使用免疫印迹和免疫组织化学来量化与 AD 相关的病理标志物。 结果：在 8 个月大的 APP/PS1 小鼠的小脑中，我们发现广泛的 Aβ 斑块被激活的小胶质细胞包围，通过离子化的钙结合衔接分子 (Iba1) 检测到，但与星形胶质细胞标志物胶质纤维酸性蛋白 (GFAP) 相比没有增加控制。有趣的是，在 APP/PS1 和对照小鼠之间，突触前标志物 syntaxin1A 和突触后标志物 spinophilin 没有差异。 Palm11-PrRP31 治疗显着降低了小脑中的 Aβ 斑块负荷和小胶质细胞增生。此外，palm11-PrRP31 增加突触发生并减轻 APP/PS1 小鼠海马的神经炎症和细胞凋亡。 结论：这些结果表明 palm11-PrRP31 是一种有前途的治疗神经退行性疾病的药物。

关键词: APP/PS1 小鼠、阿尔茨海默病、palm11-PrRP31、海马、小脑、淀粉样蛋白-β 斑块、神经炎症、突触发生。

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