{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:46:45Z","timestamp":1790351205537,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T00:00:00Z","timestamp":1589760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"am","delay-in-days":359,"URL":"http:\/\/rsc.li\/journals-terms-of-use"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01 ES010563"],"award-info":[{"award-number":["R01 ES010563"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01 ES016931"],"award-info":[{"award-number":["R01 ES016931"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["T32 ES007028"],"award-info":[{"award-number":["T32 ES007028"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["R01 ES010563"],"award-info":[{"award-number":["R01 ES010563"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["R01 ES016931"],"award-info":[{"award-number":["R01 ES016931"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["T32 ES007028"],"award-info":[{"award-number":["T32 ES007028"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Manganese (Mn) is an essential micronutrient required for the proper function of several enzymes. Accumulating evidence demonstrates a selective decrease of bioavailable Mn in vulnerable cell types of Huntington\u2019s Disease (HD), an inherited progressive neurodegenerative disorder with no cure. Amelioration of underlying pathophysiology, such as alterations in Mn-dependent biology, may be therapeutic. We therefore sought to investigate global Mn-dependent and Mn-responsive biology following various Mn exposures in a mouse model of HD. YAC128 and wildtype (WT) littermate control mice received one of three different Mn exposure paradigms by subcutaneous injection of 50 mg kg\u22121 MnCl2\u00b74(H2O) across two distinct HD disease stages. \u201cPre-manifest\u201d (12-week old mice) mice received either a single (1 injection) or week-long (3 injections) exposure of Mn or vehicle (H2O) and were sacrificed at the pre-manifest stage. \u201cManifest\u201d (32-week old) mice were sacrificed following either a week-long Mn or vehicle exposure during the manifest stage, or a 20-week-long chronic (2\u00d7 weekly injections) exposure that began in the pre-manifest stage. Tissue Mn, mRNA, protein, and metabolites were measured in the striatum, the brain region most sensitive to neurodegeneration in HD. Across all Mn exposure paradigms, pre-manifest YAC128 mice exhibited a suppressed response to transcriptional and protein changes and manifest YAC128 mice showed a suppressed metabolic response, despite equivalent elevations in whole striatal Mn. We conclude that YAC128 mice respond differentially to Mn compared to WT as measured by global transcriptional, translational, and metabolomic changes, suggesting an impairment in Mn homeostasis across two different disease stages in YAC128 mice.<\/jats:p>","DOI":"10.1039\/d0mt00081g","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T19:45:05Z","timestamp":1589312705000},"page":"1118-1130","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Huntington\u2019s disease genotype suppresses global manganese-responsive processes in pre-manifest and manifest YAC128 mice"],"prefix":"10.1093","volume":"12","author":[{"given":"Anna C","family":"Pfalzer","sequence":"first","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordyn 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L","family":"Parmalee","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy D","family":"Sherrod","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Vanderbilt University, Nashville, TN, USA"},{"name":"Center for Innovative Technology, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith M","family":"Erikson","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of North Carolina-Greensboro, Greensboro, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona E","family":"Harrison","sequence":"additional","affiliation":[{"name":"Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, Nashville, TN, USA"},{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"name":"Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8918-6419","authenticated-orcid":false,"given":"John A","family":"McLean","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Vanderbilt University, Nashville, TN, USA"},{"name":"Center for Innovative Technology, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Aschner","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8728-3346","authenticated-orcid":false,"given":"Aaron 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V. Bichell (ORCID)","URL":"http:\/\/orcid.org\/0000-0002-1055-4993","name":"identifier","group":{"name":"author_identifiers","label":"IDENTIFIERS"}},{"value":"John A. McLean (ORCID)","URL":"http:\/\/orcid.org\/0000-0001-8918-6419","name":"identifier","group":{"name":"author_identifiers","label":"IDENTIFIERS"}},{"value":"Aaron B. Bowman (ORCID)","URL":"http:\/\/orcid.org\/0000-0001-8728-3346","name":"identifier","group":{"name":"author_identifiers","label":"IDENTIFIERS"}},{"value":"Single-blind","order":2,"name":"peer_review_method","group":{"name":"peer_review_method","label":"PEER REVIEW METHOD"}},{"value":"Received 26 March 2020; Accepted 5 May 2020;  Accepted Manuscript published 12 May 2020;  Advance Article published 18 May 2020;  Version of Record published 22 July 2020","order":1,"name":"history","group":{"name":"publication_history","label":"PUBLICATION HISTORY"}}]}}