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HD<\/jats:styled-content> is characterized by a failure in brain energy metabolism. It has been proposed that monocarboxylates, such as lactate, support brain activity. During neuronal synaptic activity, ascorbic acid released from glial cells stimulates lactate and inhibits glucose transport. The aim of this study was to evaluate the expression and function of monocarboxylate transporters (MCT<\/jats:styled-content>s) in two HD<\/jats:styled-content> models.<\/jats:p><\/jats:sec>Methods<\/jats:title>Using immunofluorescence, qPCR<\/jats:styled-content>, and Western blot analyses, we explored mRNA<\/jats:styled-content> and protein levels of MCT<\/jats:styled-content>s in the striatum of R6\/2 animals and HdhQ7\/111 cells. We also evaluated MCT<\/jats:styled-content> function in HdhQ7\/111 cells using radioactive tracers and the fluorescent lactate sensor Laconic.<\/jats:p><\/jats:sec>Results<\/jats:title>We found no significant differences in the mRNA<\/jats:styled-content> or protein levels of neuronal MCT<\/jats:styled-content>s. Functional analyses revealed that neuronal MCT<\/jats:styled-content>2 had a high catalytic efficiency in HD<\/jats:styled-content> cells. Ascorbic acid did not stimulate lactate uptake in HD<\/jats:styled-content> cells. Ascorbic acid was also unable to inhibit glucose transport in HD<\/jats:styled-content> cells because they exhibit decreased expression of the neuronal glucose transporter GLUT<\/jats:styled-content>3.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>We demonstrate that stimulation of lactate uptake by ascorbic acid is a consequence of inhibiting glucose transport. Supporting this, lactate transport stimulation by ascorbic acid in HD<\/jats:styled-content> cells was completely restored by overexpressing GLUT<\/jats:styled-content>3. Therefore, alterations in GLUT<\/jats:styled-content>3 expression could be responsible for inefficient use of lactate in HD<\/jats:styled-content> neurons, contributing to the metabolic failure observed in HD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12837","type":"journal-article","created":{"date-parts":[[2018,4,6]],"date-time":"2018-04-06T15:03:30Z","timestamp":1523027010000},"page":"343-352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Altered lactate metabolism in Huntington's disease is dependent on GLUT<\/scp>3 expression"],"prefix":"10.1111","volume":"24","author":[{"given":"Macarena","family":"Sol\u00eds\u2010Maldonado","sequence":"first","affiliation":[{"name":"Instituto de Bioqu\u00edmica y Microbiolog\u00eda Facultad de Ciencias Universidad Austral de Chile Valdivia Chile"},{"name":"Center for Interdisciplinary Studies on the Nervous System (CISNe) Universidad Austral de 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