{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:54:00Z","timestamp":1788317640571,"version":"build-2803163510"},"reference-count":92,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005378","name":"Hacettepe University","doi-asserted-by":"publisher","award":["TSA-2021-19504"],"award-info":[{"award-number":["TSA-2021-19504"]}],"id":[{"id":"10.13039\/501100005378","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>L-DOPA-induced dyskinesia (LID) remains the most challenging complication of dopamine replacement therapy in Parkinson\u2019s disease, correlated with maladaptive plasticity within corticostriatal circuits. Perineuronal nets (PNNs), extracellular matrix structures enwrapping mainly parvalbumin interneurons (PV-INs), are key regulators of neuronal stability and plasticity, yet their contribution to LID is unknown. Using a unilateral 6-hydroxydopamine rat model of Parkinsonism followed by chronic L-DOPA administration, we quantified PNN\u2013PV associations by Wisteria floribunda agglutinin (WFA) and PV immunolabeling across striatal and motor cortical territories. Dopamine loss markedly reduced PNN density and intensity in the dorsolateral striatum (DLS), which only partially recovered after L-DOPA. In LID, canonical WFA+\/PV+ cells remained low, whereas non-canonical WFA\u2212\/PV+ populations expanded in both DLS and M1 motor cortex (M1), indicating region-specific remodeling toward a high-plasticity state. To assess causality, we used Chondroitinase ABC (ChABC) for PNN degradation. DLS-targeted ChABC exacerbated abnormal involuntary movements and increased local PV density, while M1-ChABC had no behavioral effect but altered PV metrics within the DLS\u2013M1 axis. These findings identify the DLS as a critical node where PNN fragility amplifies dyskinesia, highlight a functional coupling between striatal and cortical PNN\u2013PV remodeling, and suggest that stabilizing extracellular matrix integrity could mitigate maladaptive plasticity underlying LID.<\/jats:p>","DOI":"10.3390\/ijms262311726","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T16:47:37Z","timestamp":1764780457000},"page":"11726","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Remodeling of Perineuronal Nets in the Striato-Cortical Axis in L-DOPA-Induced Dyskinesia Rat Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7915-8510","authenticated-orcid":false,"given":"Nedime Tugce","family":"Bilbay","sequence":"first","affiliation":[{"name":"Institute of Neurological Sciences and Psychiatry, Hacettepe University, 06100 Ankara, T\u00fcrkiye"},{"name":"Neurology Department, Ministry of Health Diskapi Yildirim Beyazit Training and Research Hospital, 06110 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5453-1294","authenticated-orcid":false,"given":"Banu Cahide","family":"Tel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4482-7352","authenticated-orcid":false,"given":"Gulsum","family":"Akkus","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3401-3892","authenticated-orcid":false,"given":"Canan","family":"Cakir-Aktas","sequence":"additional","affiliation":[{"name":"Institute of Neurological Sciences and Psychiatry, Hacettepe University, 06100 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9825-2115","authenticated-orcid":false,"given":"Taha","family":"Solakoglu","sequence":"additional","affiliation":[{"name":"Institute of Neurological Sciences and Psychiatry, Hacettepe University, 06100 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-7939","authenticated-orcid":false,"given":"Gul","family":"Yalcin-Cakmakli","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Hacettepe University, 06100 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5015-0152","authenticated-orcid":false,"given":"Bulent","family":"Elibol","sequence":"additional","affiliation":[{"name":"Institute of Neurological Sciences and Psychiatry, Hacettepe University, 06100 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17013","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson disease","volume":"3","author":"Poewe","year":"2017","journal-title":"Nat. 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