E. Brouillet, F. Conde, M. F. Beal, and P. Hantraye, Replicating Huntington's disease phenotype in experimental animals, Prog Neurobiol, vol.59, issue.5, pp.427-468, 1999.

. The_huntington_disease_collaborative_research_group, A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group, Cell, vol.72, issue.6, pp.971-983, 1993.

B. Kremer, P. Goldberg, S. E. Andrew, J. Theilmann, and H. Telenius, A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats, N Engl J Med, vol.330, issue.20, pp.1401-1406, 1994.

N. S. Wexler, J. Lorimer, J. Porter, F. Gomez, and C. Moskowitz, Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset, Proc Natl Acad Sci U S A, vol.101, issue.10, pp.3498-3503, 2004.

M. P. Mattson and T. Magnus, Ageing and neuronal vulnerability, Nat Rev Neurosci, vol.7, issue.4, pp.278-294, 2006.

V. A. Vernace, T. Schmidt-glenewinkel, and F. Me, Aging and regulated protein degradation: who has the UPPer hand?, Aging Cell, vol.6, issue.5, pp.599-606, 2007.

E. C. Toescu, A. Verkhratsky, and P. W. Landfield, Ca2+ regulation and gene expression in normal brain aging, Trends Neurosci, vol.27, issue.10, pp.614-620, 2004.

M. F. Beal, Mitochondria take center stage in aging and neurodegeneration, Ann Neurol, vol.58, issue.4, pp.495-505, 2005.

E. Brouillet, C. Jacquard, N. Bizat, and D. Blum, 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease, J Neurochem, vol.95, issue.6, pp.1521-1540, 2005.

G. Clarke, R. A. Collins, B. R. Leavitt, D. F. Andrews, and M. R. Hayden, A one-hit model of cell death in inherited neuronal degenerations, Nature, vol.406, issue.6792, pp.195-199, 2000.

L. P. De-almeida, C. A. Ross, D. Zala, P. Aebischer, and N. Deglon, Lentiviralmediated delivery of mutant huntingtin in the striatum of rats induces a selective neuropathology modulated by polyglutamine repeat size, huntingtin expression levels, and protein length, J Neurosci, vol.22, issue.9, pp.3473-3483, 2002.

M. Arango, S. Holbert, D. Zala, E. Brouillet, and J. Pearson, CA150 expression delays striatal cell death in overexpression and knock-in conditions for mutant huntingtin neurotoxicity, J Neurosci, vol.26, issue.17, pp.4649-4659, 2006.

R. Pardo, C. E. Regulier, E. Aebischer, P. Deglon, and N. , Inhibition of calcineurin by FK506 protects against polyglutamine-huntingtin toxicity through an increase of huntingtin phosphorylation at S421, J Neurosci, vol.26, issue.5, pp.1635-1645, 2006.

S. Palfi, E. Brouillet, B. Jarraya, J. Bloch, and C. Jan, Expression of mutated huntingtin fragment in the putamen is sufficient to produce abnormal movement in non-human primates, Mol Ther, vol.15, issue.8, pp.1444-1451, 2007.

E. Colin, E. Regulier, V. Perrin, A. Durr, and A. Brice, Akt is altered in an animal model of Huntington's disease and in patients, Eur J Neurosci, vol.21, issue.6, pp.1478-1488, 2005.

C. A. Gutekunst, S. H. Li, H. Yi, J. S. Mulroy, and S. Kuemmerle, Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology, J Neurosci, vol.19, issue.7, pp.2522-2534, 1999.

S. Kuemmerle, C. A. Gutekunst, A. M. Klein, X. J. Li, and S. H. Li, Huntington aggregates may not predict neuronal death in Huntington's disease, Ann Neurol, vol.46, issue.6, pp.842-849, 1999.

H. Li, S. H. Li, H. Johnston, P. F. Shelbourne, and X. J. Li, Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity, Nat Genet, vol.25, issue.4, pp.385-389, 2000.

H. Li, S. H. Li, Z. X. Yu, P. Shelbourne, and X. J. Li, Huntingtin aggregateassociated axonal degeneration is an early pathological event in Huntington's disease mice, J Neurosci, vol.21, issue.21, pp.8473-8481, 2001.

E. Regulier, L. Pereira-de-almeida, B. Sommer, P. Aebischer, and N. Deglon, Dose-dependent neuroprotective effect of ciliary neurotrophic factor delivered via tetracycline-regulated lentiviral vectors in the quinolinic acid rat model of Huntington's disease, Hum Gene Ther, vol.13, issue.16, pp.1981-1990, 2002.

D. L. Dickstein, D. Kabaso, A. B. Rocher, J. I. Luebke, and S. L. Wearne, Changes in the structural complexity of the aged brain, Aging Cell, vol.6, issue.3, pp.275-284, 2007.

A. Hodges, A. D. Strand, A. K. Aragaki, A. Kuhn, and T. Sengstag, Regional and cellular gene expression changes in human Huntington's disease brain, Hum Mol Genet, vol.15, issue.6, pp.965-977, 2006.

R. Luthi-carter, A. Strand, N. L. Peters, S. M. Solano, and Z. R. Hollingsworth, Decreased expression of striatal signaling genes in a mouse model of Huntington's disease, Hum Mol Genet, vol.9, issue.9, pp.1259-1271, 2000.

P. A. Desplats, K. E. Kass, T. Gilmartin, G. D. Stanwood, and E. L. Woodward, Selective deficits in the expression of striatal-enriched mRNAs in Huntington's disease, J Neurochem, vol.96, issue.3, pp.743-757, 2006.

M. Asanuma, S. Nishibayashi, E. Iwata, Y. Kondo, and T. Nakanishi, Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor, Brain Res Mol Brain Res, vol.41, issue.1-2, pp.210-215, 1996.

J. S. Steffan, A. Kazantsev, O. Spasic-boskovic, M. Greenwald, and Y. Z. Zhu, The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription, Proc Natl Acad Sci U S A, vol.97, issue.12, pp.6763-6768, 2000.

K. L. Sugars and D. C. Rubinsztein, Transcriptional abnormalities in Huntington disease, Trends Genet, vol.19, issue.5, pp.233-238, 2003.

N. Deglon and P. Aebischer, Lentiviruses as vectors for CNS diseases, Curr Top Microbiol Immunol, vol.261, pp.191-209, 2002.

N. Deglon and P. Hantraye, Viral vectors as tools to model and treat neurodegenerative disorders, J Gene Med, vol.7, issue.5, pp.530-539, 2005.

M. Difiglia, E. Sapp, K. O. Chase, S. W. Davies, and G. P. Bates, Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain, Science, vol.277, issue.5334, pp.1990-1993, 1997.

S. W. Davies, M. Turmaine, B. A. Cozens, M. Difiglia, and A. H. Sharp, Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation, Cell, vol.90, issue.3, pp.537-548, 1997.

H. Li, S. H. Li, A. L. Cheng, L. Mangiarini, and G. P. Bates, Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice, Hum Mol Genet, vol.8, issue.7, pp.1227-1236, 1999.

M. Arrasate, S. Mitra, E. S. Schweitzer, M. R. Segal, and S. Finkbeiner, Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death, Nature, vol.431, issue.7010, pp.805-810, 2004.

F. Saudou, S. Finkbeiner, D. Devys, and M. E. Greenberg, Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions, Cell, vol.95, issue.1, pp.55-66, 1998.

X. J. Li and S. H. Li, HAP1 and intracellular trafficking, Trends Pharmacol Sci, vol.26, issue.1, pp.1-3, 2005.

X. J. Li, S. H. Li, A. H. Sharp, F. C. Nucifora, and G. Schilling, A huntingtinassociated protein enriched in brain with implications for pathology, Nature, vol.378, issue.6555, pp.398-402, 1995.

M. A. Kalchman, H. B. Koide, K. Mccutcheon, R. K. Graham, and K. Nichol, HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain, Nat Genet, vol.16, issue.1, pp.44-53, 1997.

E. E. Wanker, C. Rovira, E. Scherzinger, R. Hasenbank, and S. Walter, HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system, Hum Mol Genet, vol.6, issue.3, pp.487-495, 1997.

C. E. Wang, H. Zhou, J. R. Mcguire, V. Cerullo, and B. Lee, Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin, J Cell Biol, vol.181, issue.5, pp.803-816, 2008.

S. Melov, Modeling mitochondrial function in aging neurons, Trends Neurosci, vol.27, issue.10, pp.601-606, 2004.

L. A. Loeb, D. C. Wallace, and G. M. Martin, The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations, Proc Natl Acad Sci U S A, vol.102, issue.52, pp.18769-18770, 2005.

T. Lu, Y. Pan, S. Y. Kao, C. Li, and I. Kohane, Gene regulation and DNA damage in the ageing human brain, Nature, vol.429, issue.6994, pp.883-891, 2004.

P. Mecocci, M. F. Beal, R. Cecchetti, M. C. Polidori, and A. Cherubini, Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain, Mol Chem Neuropathol, vol.31, issue.1, pp.53-64, 1997.

P. Mecocci, U. Macgarvey, A. E. Kaufman, D. Koontz, and J. M. Shoffner, Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain, Ann Neurol, vol.34, issue.4, pp.609-616, 1993.

T. Finkel and N. J. Holbrook, Oxidants, oxidative stress and the biology of ageing, Nature, vol.408, issue.6809, pp.239-247, 2000.

M. B. Bogdanov, O. A. Andreassen, A. Dedeoglu, R. J. Ferrante, and M. F. Beal, Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease, J Neurochem, vol.79, issue.6, pp.1246-1249, 2001.

M. B. Bogdanov, R. J. Ferrante, S. Kuemmerle, P. Klivenyi, and M. F. Beal, Increased vulnerability to 3-nitropropionic acid in an animal model of Huntington's disease, J Neurochem, vol.71, issue.6, pp.2642-2644, 1998.

R. J. Ferrante, O. A. Andreassen, A. Dedeoglu, K. L. Ferrante, and B. G. Jenkins, Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease, J Neurosci, vol.22, issue.5, pp.1592-1599, 2002.

K. M. Smith, S. Matson, W. R. Matson, K. Cormier, D. Signore et al., Dose ranging and efficacy study of high-dose coenzyme Q10 formulations in Huntington's disease mice, Biochim Biophys Acta, vol.1762, issue.6, pp.616-626, 2006.

S. E. Browne and M. F. Beal, Oxidative damage in Huntington's disease pathogenesis, Antioxid Redox Signal, vol.8, pp.2061-2073, 2006.

N. E. Sharpless and R. A. Depinho, Cell, vol.110, issue.1, pp.9-12, 2002.

B. I. Bae, H. Xu, S. Igarashi, M. Fujimuro, and N. Agrawal, mediates cellular dysfunction and behavioral abnormalities in Huntington's disease, Neuron, vol.47, issue.1, pp.29-41, 2005.

J. A. Parker, M. Arango, S. Abderrahmane, E. Lambert, and C. Tourette, Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons, Nat Genet, vol.37, issue.4, pp.349-350, 2005.

J. T. Rodgers, C. Lerin, W. Haas, S. P. Gygi, and B. M. Spiegelman, Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1, Nature, vol.434, issue.7029, pp.113-118, 2005.

L. Cui, H. Jeong, F. Borovecki, C. N. Parkhurst, and N. Tanese, Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration, Cell, vol.127, issue.1, pp.59-69, 2006.

P. Weydt, V. V. Pineda, A. E. Torrence, R. T. Libby, and T. F. Satterfield, Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration, Cell Metab, vol.4, issue.5, pp.349-362, 2006.

H. Zhou, F. Cao, Z. Wang, Z. X. Yu, and H. P. Nguyen, Huntingtin forms toxic NH2-terminal fragment complexes that are promoted by the agedependent decrease in proteasome activity, J Cell Biol, vol.163, issue.1, pp.109-118, 2003.

A. F. Hottinger, M. Azzouz, N. Deglon, P. Aebischer, and A. D. Zurn, Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus, J Neurosci, vol.20, issue.15, pp.5587-5593, 2000.

L. P. De-almeida, D. Zala, P. Aebischer, and N. Deglon, Neuroprotective effect of a CNTF-expressing lentiviral vector in the quinolinic acid rat model of Huntington's disease, Neurobiol Dis, vol.8, issue.3, pp.433-446, 2001.

N. Bizat, J. M. Hermel, F. Boyer, C. Jacquard, and C. Creminon, Calpain is a major cell death effector in selective striatal degeneration induced in vivo by 3-nitropropionate: implications for Huntington's disease, J Neurosci, vol.23, issue.12, pp.5020-5030, 2003.

V. Perrin, E. Regulier, T. Abbas-terki, R. Hassig, and E. Brouillet, Neuroprotection by Hsp104 and Hsp27 in lentiviral-based rat models of Huntington's disease, Mol Ther, vol.15, issue.5, pp.903-911, 2007.

R. E. Coggeshall, A consideration of neural counting methods, Trends Neurosci, vol.15, issue.1, pp.9-13, 1992.

M. D. Madeira, J. P. Andrade, A. R. Lieberman, N. Sousa, and O. F. Almeida, Chronic alcohol consumption and withdrawal do not induce cell death in the suprachiasmatic nucleus, but lead to irreversible depression of peptide immunoreactivity and mRNA levels, J Neurosci, vol.17, issue.4, pp.1302-1319, 1997.

M. J. West, L. Slomianka, and H. J. Gundersen, Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator, Anat Rec, vol.231, issue.4, pp.482-497, 1991.

G. Paxinos and C. Watson, The rat brain in stereotaxic coordinates, 1986.