{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T18:13:41Z","timestamp":1779387221475,"version":"3.53.1"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder in which gait disturbances are a major source of disability, yet their early manifestations remain difficult to characterize because prodromal PD is challenging to identify in humans. Rodent models may help address this gap by approximating partial dopaminergic loss and enabling investigation of motor changes that precede overt symptoms. Here, we examined stepping performance and velocity in Wistar rats following unilateral low-dose 6-hydroxydopamine (6-OHDA) lesions in the substantia nigra pars compacta (SNc). Animals were assessed weekly for six weeks in the horizontal ladder, where velocity and footfall errors were quantified using markerless pose estimation with DeepLabCut (DLC). Lesioned animals showed greater tyrosine hydroxylase (TH) asymmetry than controls, accompanied by persistent but gradually attenuating impairments in stepping accuracy. Footfall errors peaked around week three and remained elevated thereafter, whereas velocity showed more heterogeneous changes across time. Although sex effects were not uniformly robust, control females showed an increase in velocity across weeks, whereas lesioned females exhibited a less pronounced and more variable pattern. These findings indicate that partial SNc lesions can reveal subtle and time-dependent alterations in locomotor skills relevant to the study of early dopaminergic dysfunction. Combined with DLC-based tracking, this framework provides a practical approach for detecting early behavioral changes and refining the study of preclinical motor features of PD.<\/jats:p>","DOI":"10.1371\/journal.pone.0337381","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T17:31:36Z","timestamp":1779384696000},"page":"e0337381","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time-dependent changes in stepping performance and velocity following partial dopaminergic lesions in the SNc of male and female rats"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2543-8933","authenticated-orcid":true,"given":"Diego","family":"Lievano Parra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4473-8612","authenticated-orcid":true,"given":"Juan David","family":"Garavito Coronado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2631-3382","authenticated-orcid":true,"given":"Valeria","family":"Gonzalez Diaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Cardenas Parra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"issue":"13","key":"pone.0337381.ref001","doi-asserted-by":"crossref","first-page":"7183","DOI":"10.3390\/ijms25137183","article-title":"A Comprehensive Approach to Parkinson\u2019s Disease: Addressing Its Molecular, Clinical, and Therapeutic Aspects","volume":"25","author":"M Muleiro Alvarez","year":"2024","journal-title":"Int J Mol Sci"},{"key":"pone.0337381.ref002","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/jnc.13691","article-title":"The clinical symptoms of Parkinson\u2019s disease","author":"S Sveinbjornsdottir","year":"2016","journal-title":"J Neurochem"},{"key":"pone.0337381.ref003","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.neubiorev.2016.07.010","article-title":"Motor symptoms in Parkinson\u2019s disease: A unified framework","volume":"68","author":"AA Moustafa","year":"2016","journal-title":"Neurosci Biobehav Rev"},{"key":"pone.0337381.ref004","first-page":"73","article-title":"Animal models of Parkinson\u2019s disease and their applications","author":"MK Lee","year":"2016","journal-title":"JPRLS"},{"issue":"2","key":"pone.0337381.ref005","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1006\/exnr.2002.7891","article-title":"Modeling Parkinson\u2019s disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway","volume":"175","author":"R Deumens","year":"2002","journal-title":"Exp Neurol"},{"key":"pone.0337381.ref006","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/BF03033565","article-title":"The 6-hydroxydopamine model of Parkinson\u2019s disease","volume":"11","author":"N Simola","year":"2007","journal-title":"Neurotox Res"},{"key":"pone.0337381.ref007","doi-asserted-by":"crossref","first-page":"114011","DOI":"10.1016\/j.expneurol.2022.114011","article-title":"Rodent models for gait network disorders in Parkinson\u2019s disease - 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Elsevier"},{"key":"pone.0337381.ref014","doi-asserted-by":"crossref","first-page":"1147784","DOI":"10.3389\/fnbeh.2023.1147784","article-title":"CatWalk XT gait parameters: a review of reported parameters in pre-clinical studies of multiple central nervous system and peripheral nervous system disease models","volume":"17","author":"IK Timotius","year":"2023","journal-title":"Front Behav Neurosci"},{"issue":"15","key":"pone.0337381.ref015","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.3390\/s19153274","article-title":"Computer methods for automatic locomotion and gesture tracking in mice and small animals for neuroscience applications: A survey","volume":"19","author":"W Abbas","year":"2019","journal-title":"Sensors"},{"issue":"1","key":"pone.0337381.ref016","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s42003-022-03077-6","article-title":"A deep learning-based toolbox for Automated Limb Motion Analysis (ALMA) in murine models of neurological 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analysis after unilateral 6-OHDA lesion and transplantation of foetal dopaminergic progenitor cells in rats","volume":"199","author":"A Klein","year":"2009","journal-title":"Behav Brain Res"},{"key":"pone.0337381.ref027","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.bbr.2014.02.039","article-title":"The effects of unilateral 6-OHDA lesion in medial forebrain bundle on the motor, cognitive dysfunctions and vulnerability of different striatal interneuron types in rats","volume":"266","author":"Y Ma","year":"2014","journal-title":"Behav Brain Res"},{"issue":"11","key":"pone.0337381.ref028","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1093\/brain\/awae210","article-title":"Neurophysiological markers of motor compensatory mechanisms in early Parkinson\u2019s disease","volume":"147","author":"M 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medication","volume":"11","author":"A Dagay","year":"2025","journal-title":"NPJ Parkinsons Dis"},{"issue":"1","key":"pone.0337381.ref035","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41531-022-00344-5","article-title":"Cognition as a mediator for gait and balance impairments in GBA-related Parkinson\u2019s disease","volume":"8","author":"R Morris","year":"2022","journal-title":"NPJ Parkinsons Dis"},{"issue":"6","key":"pone.0337381.ref036","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1007\/s00415-019-09642-0","article-title":"The motor prodromes of parkinson\u2019s disease: from bedside observation to large-scale application","volume":"268","author":"C Simonet","year":"2021","journal-title":"J Neurol"},{"issue":"1","key":"pone.0337381.ref037","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13293-025-00692-w","article-title":"Sex and gender differences in the molecular etiology of Parkinson\u2019s disease: considerations for study design and data analysis","volume":"16","author":"SL Schaffner","year":"2025","journal-title":"Biol Sex Differ"},{"issue":"1","key":"pone.0337381.ref038","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41531-024-00646-w","article-title":"Differences in brain aging between sexes in Parkinson\u2019s disease","volume":"10","author":"I Beheshti","year":"2024","journal-title":"NPJ Parkinsons Dis"},{"issue":"17","key":"pone.0337381.ref039","doi-asserted-by":"crossref","first-page":"21266","DOI":"10.1007\/s11356-020-11985-5","article-title":"Recuperative effect of estrogen on rotenone-induced experimental model of Parkinson\u2019s disease in rats","volume":"28","author":"M Makav","year":"2021","journal-title":"Environ Sci Pollut Res Int"},{"issue":"1","key":"pone.0337381.ref040","doi-asserted-by":"crossref","first-page":"10531","DOI":"10.1038\/s41598-019-47026-6","article-title":"Beneficial effect of estrogen on nigrostriatal dopaminergic neurons in drug-na\u00efve postmenopausal Parkinson\u2019s disease","volume":"9","author":"YH Lee","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0337381.ref041","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40035-023-00368-8","article-title":"Animal models of Parkinson\u2019s disease: bridging the gap between disease hallmarks and research questions","volume":"12","author":"A Dovonou","year":"2023","journal-title":"Transl Neurodegener"},{"key":"pone.0337381.ref042","doi-asserted-by":"crossref","unstructured":"P\u00e9rot JB, Ruze A, Gaurav R, Rebbah S, Cadin C, Le Troter A, et al. Longitudinal neuromelanin changes in prodromal and early Parkinson\u2019s disease in humans and rat model [Internet]. Neuroscience; 2024 [cited 2025 Aug 21]. Available from: https:\/\/doi.org\/10.1101\/2024.10.22.619619","DOI":"10.1101\/2024.10.22.619619"},{"key":"pone.0337381.ref043","author":"A Mathis","year":"2018"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0337381","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T17:31:43Z","timestamp":1779384703000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0337381"}},"subtitle":[],"editor":[{"given":"Nafisa M.","family":"Jadavji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0337381","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]}}}