{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:30:51Z","timestamp":1788481851090,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP200102445"],"award-info":[{"award-number":["DP200102445"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>L\u2010Dopa, while treating motor symptoms of Parkinson's disease, can lead to debilitating L\u2010Dopa\u2010induced dyskinesias, limiting its use. To investigate the causative relationship between neuro\u2010inflammation and dyskinesias, we assessed if striatal M1 and M2 microglia numbers correlated with dyskinesia severity and whether the anti\u2010inflammatories, minocycline and indomethacin, reverse these numbers and mitigate against dyskinesia. In 6\u2010OHDA lesioned mice, we used stereology to assess numbers of striatal M1 and M2 microglia populations in non\u2010lesioned (na\u00efve) and lesioned mice that either received no L\u2010Dopa (PD), remained non\u2010dyskinetic even after L\u2010Dopa (non\u2010LID) or became dyskinetic after L\u2010Dopa treatment (LID). We also assessed the effect of minocycline\/indomethacin treatment on striatal M1 and M2 microglia and its anti\u2010dyskinetic potential via AIMs scoring. We report that L\u2010Dopa treatment leading to LIDs exacerbates activated microglia numbers beyond that associated with the PD state; the severity of LIDs is strongly correlated to the ratio of the striatal M1 to M2 microglial numbers; in non\u2010dyskinetic mice, there is no M1\/M2 microglia ratio increase above that seen in PD mice; and reducing M1\/M2 microglia ratio using anti\u2010inflammatories is anti\u2010dyskinetic. Parkinson's disease is associated with increased inflammation, but this is insufficient to underpin dyskinesia. Given that L\u2010Dopa\u2010treated non\u2010LID mice show the same ratio of M1\/M2 microglia as PD mice that received no L\u2010Dopa, and, given minocycline\/indomethacin reduces both the ratio of M1\/M2 microglia and dyskinesia severity, our data suggest the increased microglial M1\/M2 ratio that occurs following L\u2010Dopa treatment is a contributing cause of dyskinesias.<\/jats:p>","DOI":"10.1111\/jnc.15993","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T06:10:36Z","timestamp":1698905436000},"page":"633-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The ratio of\n                    <scp>M1<\/scp>\n                    to\n                    <scp>M2<\/scp>\n                    microglia in the striatum determines the severity of\n                    <scp>L\u2010Dopa<\/scp>\n                    \u2010induced dyskinesias"],"prefix":"10.1111","volume":"167","author":[{"given":"Peggy","family":"Rentsch","sequence":"first","affiliation":[{"name":"St. Vincent's Centre for Applied Medical Research  Sydney New South Wales Australia"},{"name":"UNSW St Vincent's Clinical School, Faculty of Medicine University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Egan","sequence":"additional","affiliation":[{"name":"St. Vincent's Centre for Applied Medical Research  Sydney New South Wales Australia"},{"name":"UNSW St Vincent's Clinical School, Faculty of Medicine University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Kuriakose","sequence":"additional","affiliation":[{"name":"Centre for Motor Neuron Disease Research, Macquarie Medical School, Faculty of Medicine Macquarie University  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy","family":"Stayte","sequence":"additional","affiliation":[{"name":"St. Vincent's Centre for Applied Medical Research  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8860-8050","authenticated-orcid":false,"given":"Bryce","family":"Vissel","sequence":"additional","affiliation":[{"name":"St. Vincent's Centre for Applied Medical Research  Sydney New South Wales Australia"},{"name":"UNSW St Vincent's Clinical School, Faculty of Medicine University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-11-276"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.1090"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14450-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.07.016"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525528113"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27799"},{"key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.nbd.2014.10.017","article-title":"Glial activation is associated with l\u2010DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson's disease","volume":"73","author":"Bortolanza M.","year":"2014","journal-title":"Neurobiology of Disease"},{"issue":"2","key":"e_1_2_12_9_1","first-page":"9","article-title":"Ratings of L\u2010DOPA\u2010induced dyskinesia in the unilateral 6\u2010OHDA lesion model of Parkinson's disease in rats and mice","volume":"41","author":"Cenci M. A.","year":"2007","journal-title":"Current Protocols in Neuroscience"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.06.013"},{"key":"e_1_2_12_11_1","first-page":"286","article-title":"Temporal characterization of microglia\/macrophage phenotypes in a mouse model of neonatal hypoxic\u2010ischemic brain injury","volume":"10","author":"Erkenstam N. H.","year":"2016","journal-title":"Frontiers in Cellular Neuroscience"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.013"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.010"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4784268"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1987.tb02837.x"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.11.004"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100616-060509"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21743"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20324"},{"issue":"12","key":"e_1_2_12_20_1","first-page":"1","article-title":"The complexity of NF\u2010\u03baB signaling in inflammation and cancer","volume":"121","author":"Hoesel B.","year":"2013","journal-title":"Molecular Cancer"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat7554"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00198"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3257-09.2009"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.54"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2017.23"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23219"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.01.007"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-2012-120103"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.38.8.1285"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00234.2018"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11040691"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2013.07.002"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2016.09.013"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13139"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1040"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-010-0428-1"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.104646"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-019-0487-7"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3086"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.09.001"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124325"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167211"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019101997"},{"issue":"53","key":"e_1_2_12_44_1","first-page":"1181","article-title":"Differential roles of M1 and M2 microglia in neurodegenerative diseases","volume":"532","author":"Tang Y.","year":"2015","journal-title":"Molecular Neurobiology"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3791\/3234"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-018-1900-6"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2002.0499"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.625166"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0288-13.2013"},{"issue":"11","key":"e_1_2_12_50_1","first-page":"433","article-title":"The dynamics of microglial polarization reveal the resident neuroinflammatory responses after subarachnoid hemorrhage","volume":"113","author":"Zheng Z. V.","year":"2019","journal-title":"Translational Stroke Research"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2017.00077"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15993","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15993","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T10:26:41Z","timestamp":1703154401000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.15993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,2]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1111\/jnc.15993"],"URL":"https:\/\/doi.org\/10.1111\/jnc.15993","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JNC.15993\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.15993\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.15993\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.15993\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.15993\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.15993\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.15993\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,2]]},"assertion":[{"value":"2023-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}