A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington's disease in mice
Author
dc.contributor.author
Acuña, Aníbal I.
Author
dc.contributor.author
Esparza, Magdalena
Author
dc.contributor.author
Kramm, Carlos
Author
dc.contributor.author
Beltrán, Felipe A.
Author
dc.contributor.author
Parra, Alejandra V.
Author
dc.contributor.author
Cepeda, Carlos
Author
dc.contributor.author
Toro, Carlos A.
Author
dc.contributor.author
Vidal, René L.
Author
dc.contributor.author
Hetz Flores, Claudio
Author
dc.contributor.author
Concha, Ilona I.
Author
dc.contributor.author
Brauchi, Sebastián
Author
dc.contributor.author
Levine, Michael S.
Author
dc.contributor.author
Castro, Maite A.
Admission date
dc.date.accessioned
2019-03-15T16:05:45Z
Available date
dc.date.available
2019-03-15T16:05:45Z
Publication date
dc.date.issued
2013
Cita de ítem
dc.identifier.citation
Nature Communications, Volumen 4,
Identifier
dc.identifier.issn
20411723
Identifier
dc.identifier.other
10.1038/ncomms3917
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/166051
Abstract
dc.description.abstract
Huntington's disease has been associated with a failure in energy metabolism and oxidative damage. Ascorbic acid is a powerful antioxidant highly concentrated in the brain where it acts as a messenger, modulating neuronal metabolism. Using an electrophysiological approach in R6/2 HD slices, we observe an abnormal ascorbic acid flux from astrocytes to neurons, which is responsible for alterations in neuronal metabolic substrate preferences. Here using striatal neurons derived from knock-in mice expressing mutant huntingtin (STHdhQ cells), we study ascorbic acid transport. When extracellular ascorbic acid concentration increases, as occurs during synaptic activity, ascorbic acid transporter 2 (SVCT2) translocates to the plasma membrane, ensuring optimal ascorbic acid uptake for neurons. In contrast, SVCT2 from cells that mimic HD symptoms (dubbed HD cells) fails to reach the plasma membrane under the same conditions. We reason that an early impairment of ascorbic acid uptake in HD neuron