{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T12:56:35Z","timestamp":1781787395390,"version":"3.54.5"},"reference-count":127,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Statutory Fund of the Maj Institute of Pharmacology, Polish Academy of Sciences, Krak\u00f3w, Poland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Selective proteasome inhibitors, used to model Parkinsonian-like pathology, are known to disrupt calcium homeostasis, but the role of calcium ions in dopaminergic neuron degeneration remains unclear. The present in vivo study examined the effects of a 7-day intraperitoneal administration of cinnarizine (10 or 30 mg\/kg), a voltage-gated calcium channel blocker, in rats unilaterally injected into the substantia nigra compacta (SNc) with lactacystin (Lac; 1 \u00b5g\/2 \u00b5L) or vehicle. Dopamine (DA) and its metabolites were quantified in striatal homogenates via high-performance liquid chromatography. The SN of rats treated with 10 mg\/kg cinnarizine was used for Western blot analysis of tyrosine hydroxylase (TH), while tissue from animals receiving 30 mg\/kg was processed for histological analysis of TH-immunoreactive (TH-ir) and cresyl violet (CV)-stained neurons. Significant reductions in striatal DA and its metabolites were observed one week after Lac injection, along with increased DA catabolism. Cinnarizine at both doses partially prevented DA loss and attenuated enhanced DA turnover. Moreover, 10 mg\/kg cinnarizine partially preserved TH protein levels, while 30 mg\/kg provided histological protection of TH-ir neurons in the SN. Cinnarizine was also tested in vitro in human SH-SY5Y neuroblastoma cells and primary mouse cortical neurons exposed to Lac or rotenone to further assess its neuroprotective potential. In SH-SY5Y cells, cinnarizine (1\u201310 \u00b5M) significantly increased cell viability and reduced lactate dehydrogenase release after toxin exposure. Cinnarizine failed to counteract lactacystin-induced toxicity in primary cortical neurons but markedly reduced rotenone-evoked cell death at similar concentrations. These findings indicate that cinnarizine exerts dose-dependent neuroprotective effects in vivo and selective protective actions in vitro, supporting the potential utility of voltage-gated calcium channel blockers in treating Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms26188833","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T15:39:23Z","timestamp":1757518763000},"page":"8833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cinnarizine, a Calcium Channel Blocker, Partially Prevents the Striatal Dopamine Decline and Loss of Nigral Dopamine Neurons in the Lactacystin-Induced Rat Model of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9970-8548","authenticated-orcid":false,"given":"El\u017cbieta","family":"Lorenc-Koci","sequence":"first","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-6511","authenticated-orcid":false,"given":"Tomasz","family":"Lenda","sequence":"additional","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5011-1620","authenticated-orcid":false,"given":"Jolanta","family":"Konieczny","sequence":"additional","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6789-4489","authenticated-orcid":false,"given":"Danuta","family":"Jantas","sequence":"additional","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-7105","authenticated-orcid":false,"given":"Helena","family":"Domin","sequence":"additional","affiliation":[{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev.neuro.28.061604.135718","article-title":"Molecular pathophysiology of Parkinson\u2019s disease","volume":"28","author":"Moore","year":"2005","journal-title":"Annu. 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