{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:18:31Z","timestamp":1793650711683,"version":"4.5.1"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.192409\/2018-00"],"award-info":[{"award-number":["88887.192409\/2018-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa Do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/14207-7 2017\/24304-0"],"award-info":[{"award-number":["2017\/14207-7 2017\/24304-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["201187\/2016-7"],"award-info":[{"award-number":["201187\/2016-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    The pharmacological manipulation of neuroinflammation appears to be a promising strategy to alleviate\n                    <jats:sc>l<\/jats:sc>\n                    -DOPA-induced dyskinesia (LID) in Parkinson\u2019s disease (PD). Doxycycline (Doxy), a semisynthetic brain-penetrant tetracycline antibiotic having interesting anti-inflammatory properties, we addressed the possibility that this compound could resolve LID in\n                    <jats:sc>l<\/jats:sc>\n                    -DOPA-treated C57BL\/6 mice presenting either moderate or intermediate lesions of the mesostriatal dopaminergic pathway generated by intrastriatal injections of 6-OHDA. Doxy, when given subcutaneously before\n                    <jats:sc>l<\/jats:sc>\n                    -DOPA at doses of 20\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    and 40\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    , led to significant LID reduction in mice with moderate and intermediate dopaminergic lesions, respectively. Importantly, Doxy did not reduce locomotor activity improved by\n                    <jats:sc>l<\/jats:sc>\n                    -DOPA. To address the molecular mechanism of Doxy, we sacrificed mice with mild lesions 1) to perform the immunodetection of tyrosine hydroxylase (TH) and Fos-B and 2) to evaluate a panel of inflammation markers in the striatum, such as cyclooxygenase-2 and its downstream product Prostaglandin E2 along with the cytokines TNF-\u03b1, IL-1\u03b2 and IL-6. TH-immunodetection revealed that vehicle and Doxy-treated mice had similar striatal lesions, excluding that LID improvement by Doxy could result from neurorestorative effects. Importantly, LID inhibition by Doxy was associated with decreased Fos-B and COX-2 expression and reduced levels of PGE\n                    <jats:sub>2<\/jats:sub>\n                    , TNF-\u03b1, and IL-1\u03b2 in the dorsolateral striatum of dyskinetic mice. We conclude 1) that Doxy has the potential to prevent LID regardless of the intensity of dopaminergic lesioning and 2) that the anti-inflammatory effects of Doxy probably account for LID attenuation. Overall, the present results further indicate that Doxy might represent an attractive and alternative treatment for LID in PD.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.1045465","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T01:24:24Z","timestamp":1669166664000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Doxycycline attenuates l-DOPA-induced dyskinesia through an anti-inflammatory effect in a hemiparkinsonian mouse model"],"prefix":"10.3389","volume":"13","author":[{"given":"Maur\u00edcio","family":"dos Santos Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glauce Crivelaro do","family":"Nascimento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariza","family":"Bortolanza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick Pierre","family":"Michel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Raisman-Vozari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Del Bel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"109454","DOI":"10.1016\/j.cbi.2021.109454","article-title":"The antibiotic doxycycline mimics the ngf signaling in PC12 cells: A relevant mechanism for neuroprotection","volume":"341","author":"Amaral","year":"2021","journal-title":"Chem. 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