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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function
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Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

机译：Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

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摘要

Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A2A receptor (A2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A2AR inhibition by the Food and Drug Administration-approved A2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin's antitumor activity. Collectively, our study identifies A2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments. Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

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