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Article Dans Une Revue Journal of Cerebral Blood Flow and Metabolism Année : 2014

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

Lydie Boussicault
  • Fonction : Auteur
Anne-Sophie Herard
Noel Calingasan
  • Fonction : Auteur
Fanny Petit
  • Fonction : Auteur
Carole Malgorn
  • Fonction : Auteur
Nicolas Merienne
  • Fonction : Auteur
Caroline Jan
  • Fonction : Auteur
Marie-Claude Gaillard
  • Fonction : Auteur
Rodrigo Lerchundi
  • Fonction : Auteur
Luis F. Barros
  • Fonction : Auteur
Carole Escartin
Thierry Delzescaux
  • Fonction : Auteur
Philippe Hantraye
  • Fonction : Auteur
M. Flint Beal
  • Fonction : Auteur
Emmanuel Brouillet
Celine Vega
  • Fonction : Auteur
Gilles Bonvento

Résumé

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.

Dates et versions

hal-01545792 , version 1 (23-06-2017)

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Citer

Lydie Boussicault, Anne-Sophie Herard, Noel Calingasan, Fanny Petit, Carole Malgorn, et al.. Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte-neuron interactions. Journal of Cerebral Blood Flow and Metabolism, 2014, 34 (9), pp.1500-1510. ⟨10.1038/jcbfm.2014.110⟩. ⟨hal-01545792⟩
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