Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment. Adenosinergic receptors are considered as a potential alternative in the management of several neurodegenerative disorders. However, there is no information available on the role of A2b receptor in the pathophysiology of AD. Therefore, the effect of Aβ on the level of expression of A2b receptor was investigated in discrete memory-sensitive mouse brain regions. Aβ (1–42) was injected intracerebroventricularly to healthy male mouse to induce AD-like behavioral manifestations on Day-1 (D-1) of the experimental protocol. The animals were subjected to the Morris water maze (MWM) test on D-14 to D-18. On D-18, the animals were subjected to the Y-maze test after 30 min lag to the MWM paradigm. Aβ significantly attenuated the spatial working memory in MWM and Y-maze tests. In addition, Aβ significantly increased cholinergic dysfunction in terms of decrease in the activity of ChAT and ACh level and increase in the AChE activity in the hippocampus, pre-frontal cortex and amygdala of AD-like animals. Further, there was a significant increase in the extent of apoptosis in the selected mouse brain regions. Moreover, Aβ caused a substantial reduction in the mitochondrial function, integrity and bioenergetics in all the mouse brain regions. Furthermore, there was a significant decrease in the level of expression of A2b receptors in the selected brain regions of the rodents. Hence, it can be assumed that A2b receptor downregulation could be another therapeutic target in the management of AD.

中文翻译：

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除了线粒体损伤和胆碱能功能障碍外，淀粉样蛋白 β (1-42) 还下调了记忆敏感的小鼠大脑区域的腺苷 2b 受体

摘要 阿尔茨海默病 (AD) 是一种以记忆障碍为特征的进行性神经退行性疾病。腺苷能受体被认为是治疗几种神经退行性疾病的潜在替代品。然而，没有关于 A2b 受体在 AD 病理生理学中的作用的信息。因此，在离散的记忆敏感小鼠大脑区域中研究了 Aβ 对 A2b 受体表达水平的影响。在实验方案的第 1 天 (D-1)，将 Aβ (1-42) 注射到健康雄性小鼠的脑室内以诱导 AD 样行为表现。在 D-14 至 D-18 上对动物进行莫里斯水迷宫 (MWM) 测试。在第 18 天，动物在 MWM 范式滞后 30 分钟后接受 Y 迷宫测试。在 MWM 和 Y 迷宫测试中，Aβ 显着减弱了空间工作记忆。此外，在AD样动物的海马、前额叶皮层和杏仁核中，Aβ显着增加胆碱能功能障碍，表现为ChAT活性和ACh水平降低，AChE活性增加。此外，所选小鼠大脑区域的细胞凋亡程度显着增加。此外，Aβ 导致所有小鼠大脑区域的线粒体功能、完整性和生物能量学显着降低。此外，啮齿动物选定大脑区域中 A2b 受体的表达水平显着降低。因此，可以假设 A2b 受体下调可能是 AD 管理中的另一个治疗目标。Aβ显着增加胆碱能功能障碍，表现为AD样动物海马、前额叶皮层和杏仁核中ChAT和ACh水平的活性降低和AChE活性的增加。此外，所选小鼠大脑区域的细胞凋亡程度显着增加。此外，Aβ 导致所有小鼠大脑区域的线粒体功能、完整性和生物能量学显着降低。此外，啮齿动物选定大脑区域中 A2b 受体的表达水平显着降低。因此，可以假设 A2b 受体下调可能是 AD 管理中的另一个治疗目标。Aβ显着增加胆碱能功能障碍，表现为AD样动物海马、前额叶皮层和杏仁核中ChAT和ACh水平的活性降低和AChE活性的增加。此外，所选小鼠大脑区域的细胞凋亡程度显着增加。此外，Aβ 导致所有小鼠大脑区域的线粒体功能、完整性和生物能量学显着降低。此外，啮齿动物选定大脑区域中 A2b 受体的表达水平显着降低。因此，可以假设 A2b 受体下调可能是 AD 管理中的另一个治疗目标。