Open AccessAltered lactate metabolism in Huntington's disease is dependent on GLUT 3 expression
Author(s) -
SolísMaldonado Macarena,
Miró María Paz,
Acuña Aníbal I.,
CovarrubiasPinto Adriana,
Loaiza Anitsi,
Mayorga Gonzalo,
Beltrán Felipe A.,
Cepeda Carlos,
Levine Michael S.,
Concha Ilona I.,
Bátiz Luis Federico,
Carrasco Mónica A.,
Castro Maite A.
Publication year - 2018
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12837
Subject(s) - ascorbic acid , glut3 , glucose transporter , glucose uptake , monocarboxylate transporter , western blot , endocrinology , huntington's disease , medicine , transporter , biology , stimulation , biochemistry , chemistry , glut1 , insulin , gene , disease , food science
Summary Aims Huntington'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 ( MCT s) in two HD models. Methods Using immunofluorescence, qPCR , and Western blot analyses, we explored mRNA and protein levels of MCT s 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. Results We found no significant differences in the mRNA or protein levels of neuronal MCT s. Functional analyses revealed that neuronal MCT 2 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 GLUT 3. Conclusion 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 cells was completely restored by overexpressing GLUT 3. Therefore, alterations in GLUT 3 expression could be responsible for inefficient use of lactate in HD neurons, contributing to the metabolic failure observed in HD .