{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:02:59Z","timestamp":1789588979783,"version":"build-2803163510"},"reference-count":89,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. Army Medical Research Materiel Command"},{"name":"arkinson\u2019s Research Program"},{"name":"Investigator-Initiated Research Award"},{"DOI":"10.13039\/100000005","name":"Program Announcement Funding Opportunity Announcement Number W81XWH-17-PRR-IIRA","doi-asserted-by":"publisher","award":["W81XWH1810106"],"award-info":[{"award-number":["W81XWH1810106"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Johnny Isakson Endowment"},{"name":"W. Eugene and Linda Lloyd Endowed Chair"},{"name":"Coach Mark Richt Neurological Disease Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic environmental exposure to mixtures of heavy metals like manganese (Mn) and vanadium (V) has been associated with Parkinson\u2019s disease (PD). We investigated the poorly understood neurotoxic effects of Mn\/V co-exposure on PD-relevant behavioral phenotypes in transgenic mice expressing the human alpha-synuclein (\u03b1Syn) A53T mutant. C57BL\/6 wild-type (WT) and transgenic A53T mice were intranasally co-exposed to 100 \u00b5g MnCl2 and 75 \u00b5g V2O5 five times weekly for three months, simulating a 5-day workweek. This led to significant Mn\/V accumulation in the brain. Exploratory locomotor activity declined significantly in Mn\/V-treated A53T mice, but not in Mn\/V-treated WT mice when compared to their respective vehicle controls. Motor coordination, assessed via a forced locomotor activity test, was not significantly affected in either group. In Mn\/V-treated A53T mice, olfactory deficits were present, but not in Mn\/V-treated WT mice. Behavioral despair, assessed by tail suspension and forced swim tests, was not induced by Mn\/V co-exposure in any group compared to their vehicle controls. Mn\/V-treated A53T mice exhibited anxiety-like behavior and hyperactivity. These findings suggest that Mn\/V co-exposure exacerbates neurotoxic effects in A53T mice, with a more pronounced effect in males, providing insight into the role of metal mixture exposure in environmentally linked Parkinsonism.<\/jats:p>","DOI":"10.3390\/ijms27041757","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T09:48:34Z","timestamp":1770889714000},"page":"1757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neurotoxic Effect of Manganese and Vanadium Co-Exposure in Animal Models of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Alejandra","family":"Bargues-Carot","sequence":"first","affiliation":[{"name":"Isakson Center for Neurological Disease Research, Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA"},{"name":"Iowa Center for Advanced Neurotoxicology, Department of Biomedical Science, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen","family":"Kondru","sequence":"additional","affiliation":[{"name":"Iowa Center for Advanced Neurotoxicology, Department of Biomedical Science, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3261-0485","authenticated-orcid":false,"given":"Maddlyn","family":"Haller","sequence":"additional","affiliation":[{"name":"Iowa Center for Advanced Neurotoxicology, Department of Biomedical Science, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1214-3247","authenticated-orcid":false,"given":"Gary","family":"Zenitsky","sequence":"additional","affiliation":[{"name":"Isakson Center for Neurological Disease Research, Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA"},{"name":"Iowa Center for Advanced Neurotoxicology, Department of Biomedical Science, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huajun","family":"Jin","sequence":"additional","affiliation":[{"name":"Isakson Center for Neurological Disease Research, Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA"},{"name":"Iowa Center for Advanced Neurotoxicology, Department of Biomedical Science, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vellareddy","family":"Anantharam","sequence":"additional","affiliation":[{"name":"Isakson Center for Neurological Disease Research, Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA"},{"name":"Iowa Center for Advanced Neurotoxicology, Department of Biomedical Science, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthi","family":"Kanthasamy","sequence":"additional","affiliation":[{"name":"Isakson Center for Neurological Disease Research, Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA"},{"name":"Iowa Center for Advanced Neurotoxicology, Department of Biomedical Science, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anumantha G.","family":"Kanthasamy","sequence":"additional","affiliation":[{"name":"Isakson Center for Neurological Disease Research, Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA"},{"name":"Iowa Center for Advanced Neurotoxicology, Department of Biomedical Science, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.pneurobio.2012.06.005","article-title":"Emerging roles of microglial activation and non-motor symptoms in Parkinson\u2019s disease","volume":"98","author":"Doorn","year":"2012","journal-title":"Prog. 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