{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:34:21Z","timestamp":1791221661364,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,2,25]],"date-time":"2008-02-25T00:00:00Z","timestamp":1203897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate whether the motor and neuroprotective effects of adenosine A<jats:sub>2A<\/jats:sub> receptor (A<jats:sub>2A<\/jats:sub>R) antagonists are mediated by distinct cell types in the 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) model of Parkinson's disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used the forebrain A<jats:sub>2A<\/jats:sub>R knock\u2010out mice coupled with flow cytometric analyses and intracerebroventricular injection to determine the contribution of A<jats:sub>2A<\/jats:sub>Rs in forebrain neurons and glial cells to A<jats:sub>2A<\/jats:sub>R antagonist\u2010mediated motor and neuroprotective effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The selective deletion of A<jats:sub>2A<\/jats:sub>Rs in forebrain neurons abolished the motor stimulant effects of the A<jats:sub>2A<\/jats:sub>R antagonist KW\u20106002 but did not affect acute MPTP neurotoxicity. Intracerebroventricular administration of KW\u20106002 into forebrain A<jats:sub>2A<\/jats:sub>R knock\u2010out mice reinstated protection against acute MPTP\u2010induced dopaminergic neurotoxicity and attenuated MPTP\u2010induced striatal microglial and astroglial activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>A<jats:sub>2A<\/jats:sub>R activity in forebrain neurons is critical to the control of motor activity, whereas brain cells other than forebrain neurons (likely glial cells) are important components for protection against acute MPTP toxicity. 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