{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T09:56:53Z","timestamp":1775728613263,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Parkinson\u2019s disease (PD) is a neurodegenerative disorder marked by bradykinesia, rigidity, and tremor. While deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) effectively alleviates motor symptoms, the potential of targeting the substantia nigra pars reticulata (SNr) is less understood. This study investigates the effects of mid-term DBS of the SNr on motor function and neuroplasticity in a 6-hydroxydopamine (6-OHDA) rat model of PD. Methods: Adult male Sprague-Dawley rats (280\u2013300 g) were divided into healthy control (n = 10), PD (n = 9), sham-DBS (n = 7), and SNr-DBS (n = 7) groups. Bilateral striatal 6-OHDA lesions induced PD. High-frequency (130 Hz, 60 \u00b5s) SNr-DBS was delivered for 14 days. Locomotor activity (open-field), gait (footprint method), and motor coordination (rotarod) were assessed. Tyrosine hydroxylase (TH) expression in the SN and c-Fos and BDNF expression in the cerebellum, prefrontal cortex (PFC), and ventrolateral thalamus were analyzed histologically. Results: SNr-DBS significantly improved ambulation and horizontal activity compared to the PD group (p &lt; 0.05). Gait analysis showed significant improvements in forelimb\/hindlimb stride length and stance width, while rotarod performance indicated enhanced motor coordination (p &lt; 0.05). Histology revealed increased TH expression in the SN and elevated c-Fos and BDNF levels in the cerebellum, PFC, and thalamus in the SNr-DBS group vs. PD rats (p &lt; 0.05). Conclusions: Mid-term SNr-DBS produced significant functional gains in motor activity and coordination in a 6-OHDA PD model, together with molecular evidence of dopaminergic enhancement and neuroplastic activation. These translational findings suggest that targeting the SNr may offer a clinically relevant alternative for patients with PD, particularly for those who may not optimally respond to conventional STN or GPi stimulation.<\/jats:p>","DOI":"10.3390\/medicina62040714","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T07:48:07Z","timestamp":1775720887000},"page":"714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuromodulatory Effects of Substantia Nigra Pars Reticulata Deep Brain Stimulation (SNr-DBS) in the 6-Hydroxydopamine Rat Model of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"62","author":[{"given":"Eylem","family":"Turgut","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hande","family":"Parlak","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey"},{"name":"Department of Physiology, Faculty of Medicine, Amasya University, 05000 Amasya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinar","family":"Eser","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Bursa Uludag University, 16059 Bursa, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasin","family":"Temel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Jahanshahi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands"},{"name":"Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Levent","family":"Sar\u0131kc\u0131oglu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-5544","authenticated-orcid":false,"given":"Gamze Erguler","family":"Tanr\u0131over","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanju","family":"Ucar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Istanbul Atlas University, 34408 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ersoy","family":"Kocabicak","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Istanbul Atlas University, 34408 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aysel","family":"Agar","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1080\/14737175.2016.1218278","article-title":"Parkinson\u2019s disease, antiparkinson medicines, and driving","volume":"16","year":"2016","journal-title":"Expert Rev. 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