Altered lactate metabolism in Huntington's disease is dependent on GLUT3 expression

CNS NEUROSCIENCE & THERAPEUTICS

dc.creatorSolis-Maldonado, Macarena
dc.creatorMiro, María Paz
dc.creatorAcuña, Anibal I
dc.creatorCovarrubias-Pinto, Adriana
dc.creatorLoaiza, Anitsi
dc.creatorMayorga, Gonzalo
dc.creatorBeltrán, Felipe A
dc.creatorCepeda, Carlos
dc.creatorLevine, Michael S
dc.creatorConcha, Ilona I
dc.creatorBatiz, Luis Federico
dc.creatorCarrasco, Mónica A
dc.creatorCastro-Gallastegui, Maite Aintzane
dc.date2021-08-23T22:55:22Z
dc.date2022-07-07T02:32:01Z
dc.date2021-08-23T22:55:22Z
dc.date2022-07-07T02:32:01Z
dc.date2018
dc.date.accessioned2023-08-22T00:11:12Z
dc.date.available2023-08-22T00:11:12Z
dc.identifier1151206
dc.identifier1151206
dc.identifierhttps://hdl.handle.net/10533/251611
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8299309
dc.descriptionAimsHuntington's disease (HD) is a neurodegenerative disorder characterized by progressive abnormalities in cognitive function, mental state, and motor control. HD 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 (MCTs) in two HD models. MethodsUsing immunofluorescence, qPCR, and Western blot analyses, we explored mRNA and protein levels of MCTs in the striatum of R6/2 animals and HdhQ7/111 cells. We also evaluated MCT function in HdhQ7/111 cells using radioactive tracers and the fluorescent lactate sensor Laconic. ResultsWe found no significant differences in the mRNA or protein levels of neuronal MCTs. Functional analyses revealed that neuronal MCT2 had a high catalytic efficiency in HD cells. Ascorbic acid did not stimulate lactate uptake in HD cells. Ascorbic acid was also unable to inhibit glucose transport in HD cells because they exhibit decreased expression of the neuronal glucose transporter GLUT3. ConclusionWe 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 cells was completely restored by overexpressing GLUT3. Therefore, alterations in GLUT3 expression could be responsible for inefficient use of lactate in HD neurons, contributing to the metabolic failure observed in HD.
dc.descriptionRegular 2015
dc.descriptionFONDECYT
dc.descriptionFONDECYT
dc.languageeng
dc.relationhandle/10533/111557
dc.relationhandle/10533/111541
dc.relationhandle/10533/108045
dc.relationhttps://doi.org/10.1111/cns.12837
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsinfo:eu-repo/semantics/article
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleAltered lactate metabolism in Huntington's disease is dependent on GLUT3 expression
dc.titleCNS NEUROSCIENCE & THERAPEUTICS
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/publishedVersion


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