{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:26:05Z","timestamp":1779215165524,"version":"3.51.4"},"reference-count":48,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T00:00:00Z","timestamp":1615075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We aimed to investigate A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia. A2A was studied in control Tor1a+\/+ and Tor1a+\/\u2212 knock-out mice. A2A expression was assessed by anti-A2A antibody immunofluorescence and Western blotting. The co-localization of A2A was studied in striatal cholinergic interneurons identified by anti-choline-acetyltransferase (ChAT) antibody. A2A mRNA and cyclic adenosine monophosphate (cAMP) contents were also assessed. In Tor1a+\/+, Western blotting detected an A2A 45 kDa band, which was stronger in the striatum and the globus pallidus than in the entopeduncular nucleus. Moreover, in Tor1a+\/+, immunofluorescence showed A2A roundish aggregates, 0.3\u20130.4 \u03bcm in diameter, denser in the neuropil of the striatum and the globus pallidus than in the entopeduncular nucleus. In Tor1a+\/\u2212, A2A Western blotting expression and immunofluorescence aggregates appeared either increased in the striatum and the globus pallidus, or reduced in the entopeduncular nucleus. Moreover, in Tor1a+\/\u2212, A2A aggregates appeared increased in number on ChAT positive interneurons compared to Tor1a+\/+. Finally, in Tor1a+\/\u2212, an increased content of cAMP signal was detected in the striatum, while significant levels of A2A mRNA were neo-expressed in the globus pallidus. In Tor1a+\/\u2212, opposite changes of A2A receptors\u2019 expression in the striatal-pallidal complex and the entopeduncular nucleus suggest that the pathophysiology of dystonia is critically dependent on a composite functional imbalance of the indirect over the direct pathway in basal ganglia.<\/jats:p>","DOI":"10.3390\/ijms22052691","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T20:20:43Z","timestamp":1615148443000},"page":"2691","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A2A Receptor Dysregulation in Dystonia DYT1 Knock-Out Mice"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7720-8913","authenticated-orcid":false,"given":"Vincenza","family":"D\u2019Angelo","sequence":"first","affiliation":[{"name":"Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Giorgi","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Paldino","sequence":"additional","affiliation":[{"name":"IRCCS Santa Lucia Foundation, 00179 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Cardarelli","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca R.","family":"Fusco","sequence":"additional","affiliation":[{"name":"IRCCS Santa Lucia Foundation, 00179 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Saverioni","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Sorge","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8927-7107","authenticated-orcid":false,"given":"Giuseppina","family":"Martella","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy"},{"name":"IRCCS Santa Lucia Foundation, 00179 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1544-3907","authenticated-orcid":false,"given":"Stefano","family":"Biagioni","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola B.","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8432-594X","authenticated-orcid":false,"given":"Antonio","family":"Pisani","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Sancesario","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/0166-2236(90)90007-W","article-title":"Writer\u2019s cramp","volume":"13","author":"Marsden","year":"1990","journal-title":"Trends Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1093\/brain\/121.7.1195","article-title":"The pathophysiology of primary dystonia","volume":"121","author":"Berardelli","year":"1998","journal-title":"Brain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/mds.25475","article-title":"Phenomenology and classification of dystonia: A consensus update","volume":"28","author":"Albanese","year":"2013","journal-title":"Mov. 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