Adenosine A 2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function
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 receptor (A R) and its downstream effectors, cAMP and CREB, by ci...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2022-07, Vol.119 (28), p.e2206415119 |
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| container_issue | 28 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 119 |
| creator | Oliveros, Alfredo Yoo, Ki Hyun Rashid, Mohammad Abdur Corujo-Ramirez, Ana Hur, Benjamin Sung, Jaeyun Liu, Yuanhang Hawse, John R Choi, Doo-Sup Boison, Detlev Jang, Mi-Hyeon |
| description | 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
receptor (A
R) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A
R inhibition by the Food and Drug Administration-approved A
R 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
R signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments. |
| doi_str_mv | 10.1073/pnas.2206415119 |
| format | Article |
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receptor (A
R) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A
R inhibition by the Food and Drug Administration-approved A
R 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
R signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2206415119</identifier><identifier>PMID: 35867768</identifier><language>eng</language><publisher>United States</publisher><subject>Adenosine A2 Receptor Antagonists - therapeutic use ; Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - adverse effects ; Chemotherapy-Related Cognitive Impairment - prevention & control ; Cisplatin - adverse effects ; Cognition - drug effects ; Hippocampus - drug effects ; Hippocampus - physiopathology ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells - drug effects ; Neural Stem Cells - physiology ; Neurogenesis - drug effects ; Purines - administration & dosage ; Purines - therapeutic use ; Receptor, Adenosine A2A - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2022-07, Vol.119 (28), p.e2206415119</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1509-63bfb54b02482d70f948870530e1cfc8c3a3ae26fbfa197dc16a99642aaa32b03</citedby><cites>FETCH-LOGICAL-c1509-63bfb54b02482d70f948870530e1cfc8c3a3ae26fbfa197dc16a99642aaa32b03</cites><orcidid>0000-0003-0462-3531 ; 0000-0003-0763-8835 ; 0000-0003-1088-3540</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35867768$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oliveros, Alfredo</creatorcontrib><creatorcontrib>Yoo, Ki Hyun</creatorcontrib><creatorcontrib>Rashid, Mohammad Abdur</creatorcontrib><creatorcontrib>Corujo-Ramirez, Ana</creatorcontrib><creatorcontrib>Hur, Benjamin</creatorcontrib><creatorcontrib>Sung, Jaeyun</creatorcontrib><creatorcontrib>Liu, Yuanhang</creatorcontrib><creatorcontrib>Hawse, John R</creatorcontrib><creatorcontrib>Choi, Doo-Sup</creatorcontrib><creatorcontrib>Boison, Detlev</creatorcontrib><creatorcontrib>Jang, Mi-Hyeon</creatorcontrib><title>Adenosine A 2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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
receptor (A
R) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A
R inhibition by the Food and Drug Administration-approved A
R 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
R signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.</description><subject>Adenosine A2 Receptor Antagonists - therapeutic use</subject><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Chemotherapy-Related Cognitive Impairment - prevention & control</subject><subject>Cisplatin - adverse effects</subject><subject>Cognition - drug effects</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - physiopathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neural Stem Cells - drug effects</subject><subject>Neural Stem Cells - physiology</subject><subject>Neurogenesis - drug effects</subject><subject>Purines - administration & dosage</subject><subject>Purines - therapeutic use</subject><subject>Receptor, Adenosine A2A - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtOwzAURC0EoqWwZof8A6HXjzjxMqp4SZXYwDpy7OvK0DqRnVTi76GUx2oWM2cWh5BrBrcMKrEcosm3nIOSrGRMn5A5A80KJTWckjkAr4pacjkjFzm_AYAuazgnM1HWqqpUPSexcRj7HCLShvKGJrQ4jH2i3ba378YhHRLuMY6Z2pCHrRlDLEJ0k0VHw24wIe2-2xBpxCn1G4yYQ6YmOmr7TQxj2CP1U7Rj6OMlOfNmm_HqJxfk9f7uZfVYrJ8fnlbNurCsBF0o0fmulB1wWXNXgdeyrisoBSCz3tZWGGGQK995w3TlLFNGayW5MUbwDsSCLI-_NvU5J_TtkMLOpI-WQXsw1x7Mtf_mvoibIzFM3Q7d3_5XlfgEdMdsZg</recordid><startdate>20220712</startdate><enddate>20220712</enddate><creator>Oliveros, Alfredo</creator><creator>Yoo, Ki Hyun</creator><creator>Rashid, Mohammad Abdur</creator><creator>Corujo-Ramirez, Ana</creator><creator>Hur, Benjamin</creator><creator>Sung, Jaeyun</creator><creator>Liu, Yuanhang</creator><creator>Hawse, John R</creator><creator>Choi, Doo-Sup</creator><creator>Boison, Detlev</creator><creator>Jang, Mi-Hyeon</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-0462-3531</orcidid><orcidid>https://orcid.org/0000-0003-0763-8835</orcidid><orcidid>https://orcid.org/0000-0003-1088-3540</orcidid></search><sort><creationdate>20220712</creationdate><title>Adenosine A 2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function</title><author>Oliveros, Alfredo ; 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Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A
receptor (A
R) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A
R inhibition by the Food and Drug Administration-approved A
R 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
R signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.</abstract><cop>United States</cop><pmid>35867768</pmid><doi>10.1073/pnas.2206415119</doi><orcidid>https://orcid.org/0000-0003-0462-3531</orcidid><orcidid>https://orcid.org/0000-0003-0763-8835</orcidid><orcidid>https://orcid.org/0000-0003-1088-3540</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adenosine A2 Receptor Antagonists - therapeutic use Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Chemotherapy-Related Cognitive Impairment - prevention & control Cisplatin - adverse effects Cognition - drug effects Hippocampus - drug effects Hippocampus - physiopathology Mice Mice, Inbred C57BL Neural Stem Cells - drug effects Neural Stem Cells - physiology Neurogenesis - drug effects Purines - administration & dosage Purines - therapeutic use Receptor, Adenosine A2A - metabolism |
| title | Adenosine A 2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function |
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