Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a breathing disorder associated with cognitive impairment. However, the mechanisms leading to cognitive deficits in OSAHS remain uncertain. In this study, a mouse model of chronic intermittent hypoxia (CIH) exposures were applied for simulating the deoxygenation-reoxygenation events occurring in OSAHS. The conventional adenosine A1 receptor gene (A1R) knockout mice and the A1R agonist CCPA- or antagonist DPCPX-administrated mice were utilized to determine the precise function of A1R signaling in the process of OSAHS-relevant cognitive impairment. We demonstrated that CIH induced morphological changes and apoptosis in hippocampal neurons. Further, CIH blunted hippocampal long-term potentiation (LTP) and resulted in learning/memory impairment. Disruption of adenosine A1R exacerbated morphological, cellular, and functional damage induced by CIH. In contrast, activation of adenosine A1R signaling reduced morphological changes and apoptosis of hippocampal neurons, promoted LTP, and enhanced learning and memory. A1Rs may up-regulate protein kinase C (PKC) and its subtype PKC-ζ through the activation of Gα(i) improve spatial learning and memory disorder induced by CIH in mice. Taken together, A1R signaling plays a neuroprotective role in CIH-induced cognitive dysfunction and pathological changes in the hippocampus.

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）是与认知功能障碍相关的呼吸系统疾病。但是，导致OSAHS认知缺陷的机制仍然不确定。在这项研究中，将慢性间歇性缺氧（CIH）暴露的小鼠模型用于模拟OSAHS中发生的脱氧-复氧事件。常规腺苷A1受体基因（A1R）敲除小鼠和A1R激动剂CCPA或拮抗剂DPCPX施用的小鼠被用于确定A1R信号转导在OSAHS相关的认知障碍过程中的确切功能。我们证明，CIH诱导海马神经元的形态变化和凋亡。此外，CIH使海马长期增强（LTP）变钝，并导致学习/记忆障碍。腺苷A1R的破坏加剧了CIH诱导的形态，细胞和功能损伤。相比之下，腺苷A1R信号的激活减少了海马神经元的形态变化和凋亡，促进了LTP，并增强了学习和记忆能力。A1Rs可能通过激活Gα（i）上调蛋白激酶C（PKC）及其亚型PKC-ζ，从而改善小鼠CIH诱导的空间学习和记忆障碍。在一起