A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington's disease in mice

Acuna, AI; Esparza M.; Kramm C.; Beltran, FA; Parra, AV; Cepeda, C; Toro, CA; Vidal, RL; hetz C.; Concha, II; Brauchi, S.; Levine, MS; Castro MA

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 neurons could lead to early metabolic failure promoting neuronal death.

Más información

Título según WOS: A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington's disease in mice
Título según SCOPUS: A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington's disease in mice
Título de la Revista: NATURE COMMUNICATIONS
Volumen: 4
Editorial: NATURE PORTFOLIO
Fecha de publicación: 2013
Idioma: English
URL: http://www.nature.com/doifinder/10.1038/ncomms3917
DOI:

10.1038/ncomms3917

Notas: ISI, SCOPUS