{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T13:19:03Z","timestamp":1772457543664,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is characterized by progressive degeneration of nigrostriatal dopaminergic neurons, leading to motor dysfunction and compensatory postsynaptic dopamine receptor alterations. Valproic acid (VPA), a histone deacetylase inhibitor, has shown neuroprotective properties; however, its dose-dependent effects on dopaminergic integrity and dopamine D2 receptor (D2R) regulation remain unclear. Adult male Wistar rats received VPA (200 or 400 mg\/kg, p.o.) or vehicle for 20 days prior to unilateral 6-hydroxydopamine (6-OHDA) lesioning. Motor performance was evaluated using the beam balance test, exploratory behavior in the open field, striatal dopamine levels by PLC-electrochemical detection, and D2R protein expression by Western blot. The 6-OHDA lesion induced marked motor deficits, reduced striatal dopamine content, and significantly increased D2R expression. VPA at 200 mg\/kg produced only minor, non-significant effects. In contrast, VPA at 400 mg\/kg preserved motor performance, attenuated dopamine depletion, and normalized striatal D2R expression. These findings demonstrate a clear dose-dependent neuroprotective effect of VPA and indicate that stabilization of postsynaptic D2R expression accompanies preservation of dopaminergic terminals in the 6-OHDA rat model.<\/jats:p>","DOI":"10.3390\/ijms27052320","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:39:56Z","timestamp":1772455196000},"page":"2320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose-Dependent Neuroprotective Effects of Valproate on Motor Function and Striatal D2 Receptor Stability in a 6-OHDA Rat Model of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4599-1253","authenticated-orcid":false,"given":"Alfonso","family":"Alfaro-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Divisi\u00f3n de Neurociencias B\u00e1sicas, Instituto Nacional de Rehabilitaci\u00f3n-LGII, M\u00e9xico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ang\u00e9lica","family":"Gonz\u00e1lez-Maciel","sequence":"additional","affiliation":[{"name":"Laboratorio de Morfolog\u00eda Celular y Tisular, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, M\u00e9xico City 04300, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8916-0814","authenticated-orcid":false,"given":"Samuel Reyes","family":"Long","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Neurociencias B\u00e1sicas, Instituto Nacional de Rehabilitaci\u00f3n-LGII, M\u00e9xico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"P\u00e9rez-Guille","sequence":"additional","affiliation":[{"name":"Translational Research Center, Instituto Nacional de Pediatr\u00eda, Mexico City 04300, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa Eugenia","family":"Soriano-Rosales","sequence":"additional","affiliation":[{"name":"Translational Research Center, Instituto Nacional de Pediatr\u00eda, Mexico City 04300, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5444-270X","authenticated-orcid":false,"given":"Jos\u00e9 Francisco","family":"Gonzalez-Zamora","sequence":"additional","affiliation":[{"name":"Translational Research Center, Instituto Nacional de Pediatr\u00eda, Mexico City 04300, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herlinda","family":"Bonilla-Jaime","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda de la Reproducci\u00f3n, Universidad Aut\u00f3noma Metropolitana, Ciudad de M\u00e9xico 09340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9410-8535","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Cortes-Altamirano","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Neurociencias B\u00e1sicas, Instituto Nacional de Rehabilitaci\u00f3n-LGII, M\u00e9xico City 14389, Mexico"},{"name":"Departamento de Investigaci\u00f3n, Universidad Estatal del Valle de Ecatepec, Ecatepec de Morelo 55210, Mexico"},{"name":"Laboratorio Nacional CONAHCyT en Inteligencia artificial y Ciencia de Datos (LNC-IACD), Ecatepec de Morelo 55210, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,1]]},"reference":[{"key":"ref_1","first-page":"S3","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. 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