title: Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte-neuron interactions.
abstract: 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.
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Boussicault
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Hérard
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College, Cornell University, New York, New York, USA.
authors.forename: Noel
authors.initials: N
authors.lastname: Calingasan
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Petit
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Malgorn
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Merienne
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jan
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gaillard
authors.affiliation: Centro de Estudios Cientificos, Valdivia, Chile, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Lerchundi
authors.affiliation: Centro de Estudios Cientificos, Valdivia, Chile, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Barros
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Escartin
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Delzescaux
authors.affiliation: Université Pierre et Marie Curie (UPMC) and CNRS UMR 7102, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Mariani
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantraye
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College, Cornell University, New York, New York, USA.
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Brouillet
authors.affiliation: Université Pierre et Marie Curie (UPMC) and CNRS UMR 7102, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Véga
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Research Center (MIRCen) and CNRS CEA URA 2210, Fontenay-aux-Roses, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Bonvento
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004734:Energy Metabolism; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D019680:Trinucleotide Repeat Expansion