Behavioral and metabolic characterization of heterozygous and homozygous POLG mutator mice

Mitochondrion

Volumn 13, Issue 4, 2013, Pages 282-291

  Dai, Ying ^a   Kiselak, Tomas ^a   Clark, Joanne ^a   Clore, Elizabeth ^a   Zheng, Kangni ^a   Cheng, Allen ^a   Kujoth, Gregory C ^b   Prolla, Tomas A ^b   Maratos Flier, Eleftheria ^a   Simon, David K ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

Behavioral deficits; Dopamine; Metabolic deficits; MtDNA mutation; MtDNA polymerase ; Parkinson's disease

Indexed keywords

PROSTAGLANDIN SYNTHASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE);

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR DISORDER; CONTROLLED STUDY; DNA CONTENT; DOPAMINERGIC SYSTEM; ENZYME ACTIVITY; GENE; GENE DOSAGE; GENE MUTATION; HETEROZYGOSITY; HOMOZYGOSITY; LOCOMOTION; METABOLIC DISORDER; METABOLIC RATE; MITOCHONDRIAL DNA POLYMERASE GAMMA GENE; MITOCHONDRIAL ENERGY TRANSFER; MOTOR COORDINATION; MOTOR PERFORMANCE; MOUSE; NONHUMAN; OXYGEN CONSUMPTION; PRIORITY JOURNAL; PSYCHOLOGICAL BALANCE; ROTAROD TEST; THERMOGENESIS;

ANIMALS; DNA, MITOCHONDRIAL; DNA-DIRECTED DNA POLYMERASE; GAIT DISORDERS, NEUROLOGIC; HETEROZYGOTE; HOMOZYGOTE; HOT TEMPERATURE; MICE; MITOCHONDRIA; MUTATION; OXYGEN CONSUMPTION; VISUAL CORTEX;

MUS;

EID: 84876439613     PISSN: 15677249     EISSN: 18728278     Source Type: Journal    
DOI: 10.1016/j.mito.2013.03.006     Document Type: Article

References (48)

1. Badman M.K., Koester A., Flier J.S., Kharitonenkov A., Maratos-Flier E. Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis. Endocrinology 2009, 150:4931-4940.
2. Bender A., Krishnan K.J., Morris C.M., Taylor G.A., Reeve A.K., Perry R.H., Jaros E., Hersheson J.S., Betts J., Klopstock T., Taylor R.W., Turnbull D.M. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat. Genet. 2006, 38:515-517.
3. Betts-Henderson J., Jaros E., Krishnan K.J., Perry R.H., Reeve A.K., Schaefer A.M., Taylor R.W., Turnbull D.M. Alpha-synuclein pathology and Parkinsonism associated with POLG1 mutations and multiple mitochondrial DNA deletions. Neuropathol. Appl. Neurobiol. 2009, 35:120-124.
4. Burns R.S., LeWitt P.A., Ebert M.H., Pakkenberg H., Kopin I.J. The clinical syndrome of striatal dopamine deficiency. Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). N. Engl. J. Med. 1985, 312:1418-1421.
5. Cantuti-Castelvetri I., Lin M.T., Zheng K., Keller-McGandy C.E., Betensky R.A., Johns D.R., Beal M.F., Standaert D.G., Simon D.K. Somatic mitochondrial DNA mutations in single neurons and glia. Neurobiol. Aging 2005, 26:1343-1355.
6. Chen A.S., Metzger J.M., Trumbauer M.E., Guan X.M., Yu H., Frazier E.G., Marsh D.J., Forrest M.J., Gopal-Truter S., Fisher J., Camacho R.E., Strack A.M., Mellin T.N., MacIntyre D.E., Chen H.Y., Van der Ploeg L.H. Role of the melanocortin-4 receptor in metabolic rate and food intake in mice. Transgenic Res. 2000, 9:145-154.
7. Chen M.L., Logan T.D., Hochberg M.L., Shelat S.G., Yu X., Wilding G.E., Tan W., Kujoth G.C., Prolla T.A., Selak M.A., Kundu M., Carroll M., Thompson J.E. Erythroid dysplasia, megaloblastic anemia, and impaired lymphopoiesis arising from mitochondrial dysfunction. Blood 2009, 114:4045-4053.
8. Clark J., Clore E.L., Zheng K., Adame A., Masliah E., Simon D.K. Oral N-acetyl-cysteine attenuates loss of dopaminergic terminals in alpha-synuclein overexpressing mice. PLoS One 2010, 5:e12333.
9. Clark J., Dai Y., Simon D.K. Do somatic mitochondrial DNA mutations contribute to Parkinson's disease?. Park. Dis. 2011, 2011:659694.
10. Corral-Debrinski M., Horton T., Lott M.T., Shoffner J.M., Beal M.F., Wallace D.C. Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. Nat. Genet. 1992, 2:324-329.
11. Cruz-Sanchez F.F., Cardozo A., Tolosa E. Neuronal changes in the substantia nigra with aging: a Golgi study. J. Neuropathol. Exp. Neurol. 1995, 54:74-81.
12. Edgar D., Shabalina I., Camara Y., Wredenberg A., Calvaruso M.A., Nijtmans L., Nedergaard J., Cannon B., Larsson N.G., Trifunovic A. Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metab. 2009, 10:131-138.
13. Emborg M.E., Ma S.Y., Mufson E.J., Levey A.I., Taylor M.D., Brown W.D., Holden J.E., Kordower J.H. Age-related declines in nigral neuronal function correlate with motor impairments in rhesus monkeys. J. Comp. Neurol. 1998, 401:253-265.
14. Fearnley J.M., Lees A.J. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain 1991, 114(Pt 5):2283-2301.
15. Fulton S., Pissios P., Manchon R.P., Stiles L., Frank L., Pothos E.N., Maratos-Flier E., Flier J.S. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 2006, 51:811-822.
16. Guttman M., Burkholder J., Kish S.J., Hussey D., Wilson A., DaSilva J., Houle S. [11C]RTI-32 PET studies of the dopamine transporter in early dopa-naive Parkinson's disease: implications for the symptomatic threshold. Neurology 1997, 48:1578-1583.
17. Hattori N., Tanaka M., Ozawa T., Mizuno Y. Immunohistochemical studies on complexes I, II, III, and IV of mitochondria in Parkinson's disease. Ann. Neurol. 1991, 30:563-571.
18. Hiona A., Sanz A., Kujoth G.C., Pamplona R., Seo A.Y., Hofer T., Someya S., Miyakawa T., Nakayama C., Samhan-Arias A.K., Servais S., Barger J.L., Portero-Otin M., Tanokura M., Prolla T.A., Leeuwenburgh C. Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice. PLoS One 2010, 5:e11468.
19. Hudson G., Schaefer A.M., Taylor R.W., Tiangyou W., Gibson A., Venables G., Griffiths P., Burn D.J., Turnbull D.M., Chinnery P.F. Mutation of the linker region of the polymerase gamma-1 (POLG1) gene associated with progressive external ophthalmoplegia and Parkinsonism. Arch. Neurol. 2007, 64:553-557.
20. Inoue H., Lin L., Lee X., Shao Z., Mendes S., Snodgrass-Belt P., Sweigard H., Engber T., Pepinsky B., Yang L., Beal M.F., Mi S., Isacson O. Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:14430-14435.
21. Invernizzi F., Varanese S., Thomas A., Carrara F., Onofrj M., Zeviani M. Two novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism. Neuromuscul. Disord. 2008, 18:460-464.
22. Kelly P.H., Seviour P.W., Iversen S.D. Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res. 1975, 94:507-522.
23. Khrapko K., Kraytsberg Y., de Grey A.D., Vijg J., Schon E.A. Does premature aging of the mtDNA mutator mouse prove that mtDNA mutations are involved in natural aging?. Aging Cell 2006, 5:279-282.
24. Kokkotou E., Jeon J.Y., Wang X., Marino F.E., Carlson M., Trombly D.J., Maratos-Flier E. Mice with MCH ablation resist diet-induced obesity through strain-specific mechanisms. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2005, 289:R117-R124.
25. Koprich J.B., Reske-Nielsen C., Mithal P., Isacson O. Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease. J. Neuroinflammation 2008, 5:8.
26. Kraytsberg Y., Kudryavtseva E., McKee A.C., Geula C., Kowall N.W., Khrapko K. Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat. Genet. 2006, 38:518-520.
27. Kujoth G.C., Hiona A., Pugh T.D., Someya S., Panzer K., Wohlgemuth S.E., Hofer T., Seo A.Y., Sullivan R., Jobling W.A., Morrow J.D., Van Remmen H., Sedivy J.M., Yamasoba T., Tanokura M., Weindruch R., Leeuwenburgh C., Prolla T.A. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 2005, 309:481-484.
28. Langston J.W., Ballard P., Tetrud J.W., Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983, 219:979-980.
29. Larsson N.G. Somatic mitochondrial DNA mutations in mammalian aging. Annu. Rev. Biochem. 2010, 79:683-706.
30. Lexell J., Taylor C.C., Sjostrom M. What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men. J. Neurol. Sci. 1988, 84:275-294.
31. Lin M.T., Cantuti-Castelvetri I., Zheng K., Jackson K.E., Tan Y.B., Arzberger T., Lees A.J., Betensky R.A., Beal M.F., Simon D.K. Somatic mitochondrial DNA mutations in early Parkinson and incidental Lewy body disease. Ann. Neurol. 2012, 71:850-854.
32. Linnane A.W., Marzuki S., Ozawa T., Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet 1989, 1:642-645.
33. Luoma P., Melberg A., Rinne J.O., Kaukonen J.A., Nupponen N.N., Chalmers R.M., Oldfors A., Rautakorpi I., Peltonen L., Majamaa K., Somer H., Suomalainen A. Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Lancet 2004, 364:875-882.
34. Ma S.Y., Roytt M., Collan Y., Rinne J.O. Unbiased morphometrical measurements show loss of pigmented nigral neurones with ageing. Neuropathol. Appl. Neurobiol. 1999, 25:394-399.
35. Masliah E., Rockenstein E., Veinbergs I., Mallory M., Hashimoto M., Takeda A., Sagara Y., Sisk A., Mucke L. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 2000, 287:1265-1269.
36. Pakkenberg B., Moller A., Gundersen H.J., Mouritzen Dam A., Pakkenberg H. The absolute number of nerve cells in substantia nigra in normal subjects and in patients with Parkinson's disease estimated with an unbiased stereological method. J. Neurol. Neurosurg. Psychiatry 1991, 54:30-33.
37. Parker W.D., Boyson S.J., Parks J.K. Abnormalities of the electron transport chain in idiopathic Parkinson's disease. Ann. Neurol. 1989, 26:719-723.
38. Pickrell A.M., Pinto M., Hida A., Moraes C.T. Striatal dysfunctions associated with mitochondrial DNA damage in dopaminergic neurons in a mouse model of Parkinson's disease. J. Neurosci. 2011, 31:17649-17658.
39. Rudow G., O'Brien R., Savonenko A.V., Resnick S.M., Zonderman A.B., Pletnikova O., Marsh L., Dawson T.M., Crain B.J., West M.J., Troncoso J.C. Morphometry of the human substantia nigra in ageing and Parkinson's disease. Acta Neuropathol. 2008, 115:461-470.
40. Safdar A., Bourgeois J.M., Ogborn D.I., Little J.P., Hettinga B.P., Akhtar M., Thompson J.E., Melov S., Mocellin N.J., Kujoth G.C., Prolla T.A., Tarnopolsky M.A. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:4135-4140.
41. Schapira A.H., Cooper J.M., Dexter D., Jenner P., Clark J.B., Marsden C.D. Mitochondrial complex I deficiency in Parkinson's disease. Lancet 1989, 1:1269.
42. Severson J.A., Marcusson J., Winblad B., Finch C.E. Age-correlated loss of dopaminergic binding sites in human basal ganglia. J. Neurochem. 1982, 39:1623-1631.
43. Siddiqi Z., Kemper T.L., Killiany R. Age-related neuronal loss from the substantia nigra-pars compacta and ventral tegmental area of the rhesus monkey. J. Neuropathol. Exp. Neurol. 1999, 58:959-971.
44. Tatton W.G., Greenwood C.E., Verrier M.C., Holland D.P., Kwan M.M., Biddle F.E. Different rates of age-related loss for four murine monoaminergic neuronal populations. Neurobiol. Aging 1991, 12:543-556.
45. Trifunovic A., Wredenberg A., Falkenberg M., Spelbrink J.N., Rovio A.T., Bruder C.E., Bohlooly Y.M., Gidlof S., Oldfors A., Wibom R., Tornell J., Jacobs H.T., Larsson N.G. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 2004, 429:417-423.
46. Trifunovic A., Hansson A., Wredenberg A., Rovio A.T., Dufour E., Khvorostov I., Spelbrink J.N., Wibom R., Jacobs H.T., Larsson N.G. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:17993-17998.
47. Vermulst M., Bielas J.H., Kujoth G.C., Ladiges W.C., Rabinovitch P.S., Prolla T.A., Loeb L.A. Mitochondrial point mutations do not limit the natural lifespan of mice. Nat. Genet. 2007, 39:540-543.
48. Wanagat J., Cao Z., Pathare P., Aiken J.M. Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia. FASEB J. 2001, 15:322-332.