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

Alfredo Oliveros; Ki Hyun Yoo; Mohammad Abdur Rashid; Ana Corujo-Ramirez; Benjamin Hur; Jaeyun Sung; Yuanhang Liu; John R. Hawse; Doo Sup Choi; Detlev Boison; Mi Hyeon Jang

doi:10.1073/pnas.2206415119

Adenosine A_2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

Alfredo Oliveros, Ki Hyun Yoo, Mohammad Abdur Rashid, Ana Corujo-Ramirez, Benjamin Hur, Jaeyun Sung, Yuanhang Liu, John R. Hawse, Doo Sup Choi, Detlev Boison, Mi Hyeon Jang

Research output: Contribution to journal › Article › peer-review

Abstract

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 A_2A receptor (A_2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A_2AR inhibition by the Food and Drug Administration-approved A_2AR 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 A_2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.

Original language	English (US)
Article number	e2206415119
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	28
DOIs	https://doi.org/10.1073/pnas.2206415119
State	Published - Jul 12 2022

Keywords

KW-6002
adenosine A2A receptor
adult neurogenesis
chemobrain
chemotherapy-induced cognitive impairment

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.2206415119

Cite this

Oliveros, A., Yoo, K. H., Rashid, M. A., Corujo-Ramirez, A., Hur, B., Sung, J., Liu, Y., Hawse, J. R., Choi, D. S., Boison, D., & Jang, M. H. (2022). Adenosine A_2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function. Proceedings of the National Academy of Sciences of the United States of America, 119(28), Article e2206415119. https://doi.org/10.1073/pnas.2206415119

Adenosine A_2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function. / Oliveros, Alfredo; Yoo, Ki Hyun; Rashid, Mohammad Abdur et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 119, No. 28, e2206415119, 12.07.2022.

Research output: Contribution to journal › Article › peer-review

Oliveros, A, Yoo, KH, Rashid, MA, Corujo-Ramirez, A, Hur, B, Sung, J, Liu, Y, Hawse, JR , Choi, DS, Boison, D & Jang, MH 2022, 'Adenosine A_2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 28, e2206415119. https://doi.org/10.1073/pnas.2206415119

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abstract = "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.",

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