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The MitoPark (MP) mouse model of PD recapitulates several facets of Parkinson's disease, including gradual development of motor deficits, which enables the study of potential therapeutic interventions. One therapeutic strategy involves decreasing the mitochondrial metabolic load by inducing ketosis and providing an alternative energy source for neurons, leading to decreased neuronal oxidative stress. Thus, we hypothesized that administration of a ketone ester\u2013enriched diet (KEED) would improve motor and dopamine release deficits in MP mice. Motor function (rotarod and open field tests), dopamine release (fast\u2010scan cyclic voltammetry), tissue dopamine levels (gas chromatography\u2013mass spectrometry) and dopamine neurons and axons (immunofluorescence) were assessed in MP, and control mice fed either the standard or a KEED. When started on the ketone diet before motor dysfunction onset, MP mice had improved motor function relative to standard diet (SD) MP mice. While the KEED did not preserve dopamine neurons or striatal dopamine axons, dopamine release in ketone diet MP mice was greater than SD MP mice but less than control mice. In a follow\u2010up experiment, we began the ketone diet after motor dysfunction onset and observed a modest preservation of motor function in ketone diet MP mice relative to SD MP mice. The improvement in motor dysfunction indicates that a KEED or ketone supplement may have a beneficial effect on delaying motor deficit progression in Parkinson's disease.<\/jats:p>","DOI":"10.1111\/ejn.16601","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T22:19:08Z","timestamp":1731363548000},"page":"6875-6890","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ketone ester\u2013enriched diet ameliorates motor and dopamine release deficits in MitoPark mice"],"prefix":"10.1111","volume":"60","author":[{"given":"Vikrant R.","family":"Mahajan","sequence":"first","affiliation":[{"name":"Laboratory for Integrative Neuroscience National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Rockville Maryland USA"},{"name":"Laboratory for Metabolic Control National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Nadel","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Neuroscience National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Todd","family":"King","sequence":"additional","affiliation":[{"name":"Laboratory for Metabolic Control National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Pawlosky","sequence":"additional","affiliation":[{"name":"Laboratory for Metabolic Control National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret I.","family":"Davis","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Neuroscience National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Veech","sequence":"additional","affiliation":[{"name":"Laboratory for Metabolic Control National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Lovinger","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Neuroscience National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1682-128X","authenticated-orcid":false,"given":"Armando G.","family":"Salinas","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Neuroscience National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Rockville Maryland USA"},{"name":"Department of Pharmacology, Toxicology &amp; Neuroscience Louisiana State University Health Sciences Center \u2013 Shreveport  Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1239025"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14033"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1769"},{"key":"e_1_2_11_5_1","volume-title":"Ketogenic diet and metabolic therapies expanded roles in health and disease mitigation of damage from reactive oxygen species and ionizing radiation by ketone body esters","author":"Boison D.","year":"2016"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom9080388"},{"key":"e_1_2_11_7_1","first-page":"8847","article-title":"The protective effect of beta\u2010hydroxybutyric acid on renal glomerular epithelial cells in adriamycin\u2010induced injury","volume":"13","author":"Chang M. 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