Pharmacologic activation of mitochondrial biogenesis exerts widespread beneficial effects in a transgenic mouse model of Huntington's disease

Human Molecular Genetics

Volumn 21, Issue 5, 2012, Pages 1124-1137

  Johri, Ashu ^a   Calingasan, Noel Y ^a   Hennessey, Thomas M ^a   Sharma, Abhijeet ^a   Yang, Lichuan ^a   Wille, Elizabeth ^a   Chandra, Abhishek ^a   Beal, M Flint ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BEZAFIBRATE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; REACTIVE OXYGEN METABOLITE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASTROCYTOSIS; BIOGENESIS; CELL ACTIVATION; CELL VACUOLE; CONTROLLED STUDY; CORPUS STRIATUM; DRUG EFFECT; HUNTINGTON CHOREA; MITOCHONDRION; MOUSE; MUSCLE CELL; NONHUMAN; OXIDATIVE STRESS; PHENOTYPE; PRIORITY JOURNAL; SURVIVAL;

ADIPOSE TISSUE, BROWN; ANIMALS; BEZAFIBRATE; CORPUS STRIATUM; DIET; DISEASE MODELS, ANIMAL; GLIOSIS; HUNTINGTON DISEASE; MICE; MICE, TRANSGENIC; MITOCHONDRIA; MITOCHONDRIA, MUSCLE; MUSCLE FIBERS, SKELETAL; NEURONS; NEUROPROTECTIVE AGENTS; OXIDATIVE STRESS; PHENOTYPE; PPAR GAMMA; SIGNAL TRANSDUCTION; SURVIVAL RATE; TRANS-ACTIVATORS; TRANSCRIPTIONAL ACTIVATION; VACUOLES;

EID: 84863011541     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddr541     Document Type: Article

References (60)

1. Vonsattel, J.P. and DiFiglia, M. (1998) Huntington disease. J. Neuropathol. Exp. Neurol., 57, 369-384.
2. Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S.W. et al. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell, 87, 493-506.
3. Lin, J., Wu, P.H., Tarr, P.T., Lindenberg, K.S., St-Pierre, J., Zhang, C.Y., Mootha, V.K., Jager, S., Vianna, C.R., Reznick, R.M. et al. (2004) Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1a null mice. Cell, 119, 121-135.
4. Leone, T.C., Lehman, J.J., Finck, B.N., Schaeffer, P.J., Wende, A.R., Boudina, S., Courtois, M., Wozniak, D.F., Sambandam, N., Bernal-Mizrachi, C. et al. (2005) PGC-1a deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol., 3, e101.
5. St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J.M., Rhee, J., Jager, S., Handschin, C., Zheng, K., Lin, J., Yang, W. et al. (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell, 127, 397-408.
6. Browne, S.E. and Beal, M.F. (2006) Oxidative damage in Huntington's disease pathogenesis. Antioxid. Redox Signal, 8, 2061-2073.
7. Hersch, S.M., Gevorkian, S., Marder, K., Moskowitz, C., Feigin, A., Cox, M., Como, P., Zimmerman, C., Lin, M., Zhang, L. et al. (2006) Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2′dG. Neurology, 66, 250-252.
8. Cui, L., Jeong, H., Borovecki, F., Parkhurst, C.N., Tanese, N. and Krainc, D. (2006) Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell, 127, 59-69.
9. Weydt, P., Pineda, V.V., Torrence, A.E., Libby, R.T., Satterfield, T.F., Lazarowski, E.R., Gilbert, M.L., Morton, G.J., Bammler, T.K., Strand, A.D. et al. (2006) Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab., 4, 349-362.
10. Chaturvedi, R.K., Adhihetty, P., Shukla, S., Hennessy, T., Calingasan, N., Yang, L., Starkov, A., Kiaei, M., Cannella, M., Sassone, J. et al. (2009) Impaired PGC-1a function in muscle in Huntington's disease. Hum. Mol. Genet., 18, 3048-3065.
11. Chaturvedi, R.K., Calingasan, N.Y., Yang, L., Hennessey, T., Johri, A. and Beal, M.F. (2010) Impairment of PGC-1alpha expression, neuropathology and hepatic steatosis in a transgenic mouse model of Huntington's disease following chronic energy deprivation. Hum. Mol. Genet., 19, 3190-3205.
12. Lin, J., Wu, H., Tarr, P.T., Zhang, C.Y., Wu, Z., Boss, O., Michael, L.F., Puigserver, P., Isotani, E., Olson, E.N. et al. (2002) Transcriptional co-activator PGC-1a drives the formation of slow-twitch muscle fibres. Nature, 418, 797-801.
13. Gizatullina, Z.Z., Lindenberg, K.S., Harjes, P., Chen, Y., Kosinski, C.M., Landwehrmeyer, B.G., Ludolph, A.C., Striggow, F., Zierz, S. and Gellerich, F.N. (2006) Low stability of Huntington muscle mitochondria against Ca2+ in R6/2 mice. Ann. Neurol., 59, 407-411.
14. Kosinski, C.M., Schlangen, C., Gellerich, F.N., Gizatullina, Z., Deschauer, M., Schiefer, J., Young, A.B., Landwehrmeyer, G.B., Toyka, K.V., Sellhaus, B. et al. (2007) Myopathy as a first symptom of Huntington's disease in a Marathon runner. Mov. Disord., 22, 1637-1640.
15. Turner, C., Cooper, J.M. and Schapira, A.H. (2007) Clinical correlates of mitochondrial function in Huntington's disease muscle. Mov. Disord., 22, 1715-1721.
16. Kim, J., Moody, J.P., Edgerly, C.K., Bordiuk, O.L., Cormier, K., Smith, K., Beal, M.F. and Ferrante, R.J. (2010) Mitochondrial loss, dysfunction and altered dynamics in Huntington's disease. Hum. Mol. Genet., 19, 3919-3935.
17. Weydt, P., Soyal, S.M., Gellera, C., Didonato, S., Weidinger, C., Oberkofler, H., Landwehrmeyer, G.B. and Patsch, W. (2009) The gene coding for PGC-1a modifies age at onset in Huntington's disease. Mol. Neurodegener., 4, 3.
18. Taherzadeh-Fard, E., Saft, C., Andrich, J., Wieczorek, S. and Arning, L. (2009) PGC-1alpha as modifier of onset age in Huntington disease. Mol. Neurodegener., 4, 10.
19. Okamoto, S., Pouladi, M.A., Talantova, M., Yao, D., Xia, P., Ehrnhoefer, D.E., Zaidi, R., Clemente, A., Kaul, M., Graham, R.K. et al. (2009) Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin. Nat. Med., 15, 1407-1413.
20. Phan, J., Hickey, M.A., Zhang, P., Chesselet, M.F. and Reue, K. (2009) Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse models. Hum. Mol. Genet., 18, 1006-1016.
21. Wenz, T., Diaz, F., Spiegelman, B.M. and Moraes, C.T. (2008) Activation of the PPAR/PGC-1a pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype. Cell Metab., 8, 249-256.
22. Tenenbaum, A., Motro, M. and Fisman, E.Z. (2005) Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. Cardiovasc. Diabetol., 4, 14.
23. Bastin, J., Aubey, F., Rotig, A., Munnich, A. and Djouadi, F. (2008) Activation of peroxisome proliferator-activated receptor pathway stimulates the mitochondrial respiratory chain and can correct deficiencies in patients' cells lacking its components. J. Clin. Endocrinol. Metab., 93, 1433-1441.
24. Hondares, E., Mora, O., Yubero, P., Rodriguez de la Concepcion, M., Iglesias, R., Giralt, M. and Villarroya, F. (2006) Thiazolidinediones and rexinoids induce peroxisome proliferator-activated receptor-coactivator (PGC)-1a gene transcription: an autoregulatory loop controls PGC-1a expression in adipocytes via peroxisome proliferator-activated receptor-g coactivation. Endocrinology, 147, 2829-2838.
25. Wenz, T., Wang, X., Marini, M. and Moraes, C.T. (2010) A metabolic shift induced by a PPAR panagonist markedly reduces the effects of pathogenic mitochondrial tRNA mutations. J. Cell. Mol. Med., 15, 2317- 2325. doi:10.1111/j.1582-4934.2010.01223.x.
26. Huss, J.M. and Kelly, D.P. (2004) Nuclear receptor signaling and cardiac energetics. Circ. Res., 95, 568-578.
27. Lin, J., Handschin, C. and Spiegelman, B.M. (2005) Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab., 1, 361-370.
28. Menalled, L., El-Khodor, B.F., Patry, M., Suarez-Farinas, M., Orenstein, S.J., Zahasky, B., Leahy, C., Wheeler, V., Yang, X.W., MacDonald, M. et al. (2009) Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models. Neurobiol. Dis., 35, 319-336.
29. Ferrante, R.J., Andreassen, O.A., Dedeoglu, A., Ferrante, K.L., Jenkins, B.G., Hersch, S.M. and Beal, M.F. (2002) Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J. Neurosci., 22, 1592-1599.
30. Rubin, C., Knoblaugh, S. and Ladiges, W. (2003) Phenotypic characterization of genetically engineered mice. In Hau, J. and Van Hoosier, G.L. Jr (eds), Handbook of Laboratory Animal Science: Essential Principles and Practices, 2nd edn. CRC Press, Boca Raton, FL, Vol. 1, pp. 218-220.
31. Davies, S.W., Turmaine, M., Cozens, B.A., DiFiglia, M., Sharp, A.H., Ross, C.A., Scherzinger, E., Wanker, E.E., Mangiarini, L. and Bates, G.P. (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90, 537-548.
32. Yu, Z.X., Li, S.H., Evans, J., Pillarisetti, A., Li, H. and Li, X.J. (2003) Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington's disease. J. Neurosci., 23, 2193-2202.
33. Hedreen, J.C. and Folstein, S.E. (1995) Early loss of neostriatal striosome neurons in Huntington's disease. J. Neuropathol. Exp. Neurol., 54, 105-120.
34. Browne, S.E., Bowling, A.C., MacGarvey, U., Baik, M.J., Berger, S.C., Muqit, M.M., Bird, E.D. and Beal, M.F. (1997) Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann. Neurol., 41, 646-653.
35. Stack, E.C., Matson, W.R. and Ferrante, R.J. (2008) Evidence of oxidant damage in Huntington's disease: translational strategies using antioxidants. Ann. NY Acad. Sci., 1147, 79-92.
36. Cannon, B. and Nedergaard, J. (2004) Brown adipose tissue: function and physiological significance. Physiol. Rev., 84, 277-359.
37. Puigserver, P., Wu, Z., Park, C.W., Graves, R., Wright, M. and Spiegelman, B.M. (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 92, 829-839.
38. Browne, S.E. and Beal, M.F. (2004) The energetics of Huntington's disease. Neurochem. Res., 29, 531-546.
39. Beal, M.F., Brouillet, E., Jenkins, B.G., Ferrante, R.J., Kowall, N.W., Miller, J.M., Storey, E., Srivastava, R., Rosen, B.R. and Hyman, B.T. (1993) Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci., 13, 4181-4192.
40. Brouillet, E., Hantraye, P., Ferrante, R.J., Dolan, R., Leroy-Willig, A., Kowall, N.W. and Beal, M.F. (1995) Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc. Natl Acad. Sci. USA, 92, 7105-7109.
41. Xiang, Z., Valenza, M., Cui, L., Leoni, V., Jeong, H.K., Brilli, E., Zhang, J., Peng, Q., Duan, W., Reeves, S.A. et al. (2011) Peroxisome-proliferator-activated receptor gamma coactivator 1a contributes to dysmyelination in experimental models of Huntington's disease. J. Neurosci., 31, 9544-9553.
42. Hinerfeld, D., Traini, M.D., Weinberger, R.P., Cochran, B., Doctrow, S.R., Harry, J. and Melov, S. (2004) Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, and efficacious antioxidant therapy in superoxide dismutase 2 null mice. J. Neurochem., 88, 657-667.
43. Viscomi, C., Bottani, E., Civiletto, G., Cerutti, R., Moggio, M., Fagiolari, G., Schon, E.A., Lamperti, C. and Zeviani, M. (2011) In vivo correction of COX deficiency by activation of the AMPK/PGC-1a axis. Cell Metab., 14, 80-90.
44. Yatsuga, S. and Suomalainen, A. (2011) Effect of bezafibrate treatment on late-onset mitochondrial myopathy in mice. Hum. Mol. Genet., doi:10.1093/hmg/ddr482
45. Hersch, S.M. and Ferrante, R.J. (2004) Translating therapies for Huntington's disease from genetic animal models to clinical trials. NeuroRx, 1, 298-306.
46. Andreassen, O.A., Dedeoglu, A., Ferrante, R.J., Jenkins, B.G., Ferrante, K.L., Thomas, M., Friedlich, A., Browne, S.E., Schilling, G., Borchelt, D.R. et al. (2001) Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol. Dis., 8, 479-491.
47. Beal, M.F. and Ferrante, R.J. (2004) Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat. Rev. Neurosci., 5, 373-384.
48. Ferrante, R.J., Ryu, H., Kubilus, J.K., D'Mello, S., Sugars, K.L., Lee, J., Lu, P., Smith, K., Browne, S., Beal, M.F. et al. (2004) Chemotherapy for the brain: the antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington's disease. J. Neurosci., 24, 10335-10342.
49. Stack, C., Ho, D., Wille, E., Calingasan, N.Y., Williams, C., Liby, K., Sporn, M., Dumont, M. and Beal, M.F. (2010) Triterpenoids CDDO-ethyl amide and CDDO-trifluoroethyl amide improve the behavioral phenotype and brain pathology in a transgenic mouse model of Huntington's disease. Free Radic. Biol. Med., 49, 147-158.
50. Chiang, M.C., Chen, C.M., Lee, M.R., Chen, H.W., Chen, H.M., Wu, Y.S., Hung, C.H., Kang, J.J., Chang, C.P., Chang, C. et al. (2010) Modulation of energy deficiency in Huntington's disease via activation of the peroxisome proliferator-activated receptor gamma. Hum. Mol. Genet., 19, 4043-4058.
51. Quintanilla, R.A., Jin, Y.N., Fuenzalida, K., Bronfman, M. and Johnson, G.V. (2008) Rosiglitazone treatment prevents mitochondrial dysfunction in mutant huntingtin-expressing cells: possible role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in the pathogenesis of Huntington disease. J. Biol. Chem., 283, 25628-25637.
52. Wareski, P., Vaarmann, A., Choubey, V., Safiulina, D., Liiv, J., Kuum, M. and Kaasik, A. (2009) PGC-1a and PGC-1b regulate mitochondrial density in neurons. J. Biol. Chem., 284, 21379-21385.
53. Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P. et al. (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell, 127, 1109-1122.
54. Ho, D.J., Calingasan, N.Y., Wille, E., Dumont, M. and Beal, M.F. (2010) Resveratrol protects against peripheral deficits in a mouse model of Huntington's disease. Exp. Neurol., 225, 74-84.
55. Beal, M.F. (1999) Mitochondria, NO and neurodegeneration. Biochem. Soc. Symp., 66, 43-54.
56. Browne, S.E., Ferrante, R.J. and Beal, M.F. (1999) Oxidative stress in Huntington's disease. Brain Pathol., 9, 147-163.
57. Stoy, N., Mackay, G.M., Forrest, C.M., Christofides, J., Egerton, M., Stone, T.W. and Darlington, L.G. (2005) Tryptophan metabolism and oxidative stress in patients with Huntington's disease. J. Neurochem., 93, 611-623.
58. Gray, M., Shirasaki, D.I., Cepeda, C., Andre, V.M., Wilburn, B., Lu, X.H., Tao, J., Yamazaki, I., Li, S.H., Sun, Y.E. et al. (2008) Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J. Neurosci., 28, 6182-6195.
59. Johri, A., Starkov, A.A., Chandra, A., Hennessey, T., Sharma, A., Orobello, S., Squitieri, F., Yang, L. and Beal, M.F. (2011) Truncated peroxisome proliferator-activated receptor-g coactivator 1a splice variant is severely altered in Huntington's disease. Neurodegener. Dis., 8, 496-503.
60. Agarwal, R. and Chase, S.D. (2002) Rapid, fluorimetric-liquid chromatographic determination of malondialdehyde in biological samples. J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 775, 121-126.