Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: Critical role of astrocyte-neuron interactions

Lydie Boussicault, Anne Sophie Hérard, Noel Calingasan, Fanny Petit, Carole Malgorn, Nicolas Merienne, Caroline Jan, Marie Claude Gaillard, Rodrigo Lerchundi, Luis F. Barros, Carole Escartin, Thierry Delzescaux, Jean Mariani, Philippe Hantraye, M. Flint Beal, Emmanuel Brouillet, Céline Véga, Gilles Bonvento*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

55 Citas (Scopus)

Resumen

Huntington's disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the huntingtin (Htt) gene. Although early energy metabolic alterations in HD are likely to contribute to later neurodegenerative processes, the cellular and molecular mechanisms responsible for these metabolic alterations are not well characterized. Using the BACHD mice that express the full-length mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated localized in vivo changes in brain glucose use reminiscent of what is observed in premanifest HD carriers. Using biochemical, molecular, and functional analyses on different primary cell culture models from BACHD mice, we observed that mHtt does not directly affect metabolic activity in a cell autonomous manner. However, coculture of neurons with astrocytes from wild-type or BACHD mice identified mutant astrocytes as a source of adverse non-cell autonomous effects on neuron energy metabolism possibly by increasing oxidative stress. These results suggest that astrocyte-to-neuron signaling is involved in early energy metabolic alterations in HD.

Idioma originalInglés
Páginas (desde-hasta)1500-1510
Número de páginas11
PublicaciónJournal of Cerebral Blood Flow and Metabolism
Volumen34
N.º9
DOI
EstadoPublicada - 2014
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Neurología
  • Neurología clínica
  • Cardiología y medicina cardiovascular

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