AUTHOR=Zhang Yichun , Cao Hongchao , Qiu Xuehao , Xu Danfen , Chen Yifeng , Barnes Gregory N. , Tu Yunjia , Gyabaah Adwoa Takyiwaa , Gharbal Abdulla Husain Abdulla Ahmed , Peng Chenlei , Cai Jun , Cai Xiaohong 

TITLE=Neuroprotective Effects of Adenosine A1 Receptor Signaling on Cognitive Impairment Induced by Chronic Intermittent Hypoxia in Mice

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2020.00202

DOI=10.3389/fncel.2020.00202

ISSN=1662-5102

ABSTRACT=<p>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 (<italic>A1R</italic>) 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.</p>