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Given the key role for ascorbic acid (vitamin C) in dopamine synthesis and neurotransmission, we investigated whether mild cellular ascorbate deficiency accelerates dopaminergic dysfunction in the development of HD pathology and behavioral deficits. YAC128 mice expressing mutant human huntingtin were crossed with SVCT2\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice, which carry a heterozygous knockout of the sodium\u2010dependent vitamin C transporter, to generate mice with approximately 30% decreased neuronal vitamin C as well as progressive changes in dopamine signaling. Behavioral and neurochemical outcomes were assessed at early disease stages. At 14 and 20\u2009weeks, YAC128 and SVCT2\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    YAC128 mice showed similar deficits in grip strength, locomotor activity, and rotarod performance compared to controls, suggesting modest ascorbate deficiency did not accelerate motor phenotypes. Gene expression analysis revealed six significantly upregulated genes in the striatum of SVCT2\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    YAC128 mice, including those involved in dopamine synthesis, packaging, and transport. Notably, striatal dopamine and serotonin and their metabolites were decreased in both single mutant mouse lines (YAC128 and SVCT2\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    ) but without a compounding effect of the double mutation (SVCT2\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    YAC128). These results indicate that while moderate ascorbate deficiency may not worsen early behavioral phenotypes in the YAC128 model, it does impact dopamine system regulation at the molecular level. These findings highlight the potential importance of ascorbate in modifying disease progression and suggest that humans with HD, who cannot synthesize ascorbate, may be particularly vulnerable to vitamin C deficiency effects on dopamine dynamics.\n                  <\/jats:p>","DOI":"10.1111\/gbb.70023","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T22:00:12Z","timestamp":1748383212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vitamin C Transport Deficiency Alters Striatal Dopamine Gene Expression and Metabolism in\n                    <scp>YAC128<\/scp>\n                    Huntington Disease Mice"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7549-762X","authenticated-orcid":false,"given":"Adriana A.","family":"Tienda","sequence":"first","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center  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