Abstract Background Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disease. Recent studies have reported the close association between cognitive function in AD and purinergic receptors in the central nervous system. In the current study, we investigated the effect of CD73 inhibitor α, β-methylene ADP (APCP) on cognitive impairment of AD in mice, and to explore the potential underlying mechanisms. Results We found that acute administration of Aβ1–42 (i.c.v.) resulted in a significant increase in adenosine release by using microdialysis study. Chronic administration of APCP (10, 30 mg/kg) for 20 d obviously mitigated the spatial working memory impairment of Aβ1–42-treated mice in both Morris water maze (MWM) test and Y-maze test. In addition, the extracellular adenosine production in the hippocampus was inhibited by APCP in Aβ-treated mice. Further analyses indicated expression of acetyltransferase (ChAT) in hippocampus of mice of was significantly reduced, while acetylcholinesterase (AChE) expression increased, which compared to model group. We observed that APCP did not significantly alter the NLRP3 inflammasome activity in hippocampus, indicating that anti-central inflammation seems not to be involved in APCP effect. Conclusions In conclusion, we report for the first time that inhibition of CD73 by APCP was able to protect against memory loss induced by Aβ1–42 in mice, which may be due to the decrease of CD73-driven adenosine production in hippocampus. Enhancement of central cholinergic function of the central nervous system may also be involved in the effects of APCP.

中文翻译：

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CD73抑制剂α、β-亚甲基ADP通过抑制海马腺苷生成对β淀粉样蛋白诱导的认知障碍的保护作用

摘要背景阿尔茨海默病（AD）是一种慢性、进行性神经退行性疾病。最近的研究报告了 AD 的认知功能与中枢神经系统中的嘌呤能受体之间的密切关联。在目前的研究中，我们研究了 CD73 抑制剂 α, β-亚甲基 ADP (APCP) 对小鼠 AD 认知障碍的影响，并探讨了潜在的潜在机制。结果我们发现，通过使用微透析研究，Aβ1-42 (icv) 的急性给药导致腺苷释放显着增加。在莫里斯水迷宫 (MWM) 试验和 Y 迷宫试验中，慢性施用 APCP (10, 30 mg/kg) 20 天明显减轻了 Aβ1-42 治疗小鼠的空间工作记忆障碍。此外，在 Aβ 处理的小鼠中，APCP 抑制了海马中细胞外腺苷的产生。进一步分析表明，与模型组相比，小鼠海马区乙酰转移酶（ChAT）表达明显降低，乙酰胆碱酯酶（AChE）表达升高。我们观察到 APCP 没有显着改变海马中 NLRP3 炎症小体的活性，表明抗中枢炎症似乎与 APCP 作用无关。结论 总之，我们首次报道了 APCP 抑制 CD73 能够防止小鼠 Aβ1-42 诱导的记忆丧失，这可能是由于海马中 CD73 驱动的腺苷生成减少。中枢神经系统的中枢胆碱能功能的增强也可能与 APCP 的作用有关。