Mitochondrial DNA double-strand breaks in oligodendrocytes cause demyelination, axonal injury, and CNS inflammation

Journal of Neuroscience

Volumn 37, Issue 42, 2017, Pages 10185-10199

  Madsen, Pernille M ^a,b   Pinto, Milena ^c   Patel, Shreyans ^a   McCarthy, Stephanie ^a   Gao, Han ^a,c   Taherian, Mehran ^a   Karmally, Shaffiat ^a   Pereira, Claudia V ^c   Dvoriantchikova, Galina ^d   Ivanov, Dmitry ^d   Tanaka, Kenji F ^e   Moraes, Carlos T ^c   Brambilla, Roberta ^a,c  

^a UNIVERSITY OF MIAMI   (United States)

^b UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^c UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^e KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Animal model; Demyelination; Mitochondria; Multiple sclerosis; Oxidative phosphorylation; Remyelination

Indexed keywords

CYCLOOXYGENASE 1; MITOCHONDRIAL DNA; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; TOLONIUM CHLORIDE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY DETECTION; ANTIBODY LABELING; ANXIETY; ARTICLE; ASTROCYTOSIS; AXONAL INJURY; CELL COUNT; CELL INFILTRATION; CELL ISOLATION; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DEMYELINATION; DISEASE EXACERBATION; DOUBLE STRANDED DNA BREAK; ELECTRON MICROSCOPY; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; FLUORESCENCE MICROSCOPY; GENE DELETION; GENE EXPRESSION; GLIOSIS; IMMUNOHISTOCHEMISTRY; LOCOMOTION; MALE; MITOCHONDRION; MOTOR COORDINATION; MOUSE; NERVE FIBER DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NERVOUS SYSTEM PARAMETERS; NONHUMAN; OLIGODENDROGLIA; OPEN FIELD TEST; OPTIC NERVE INJURY; PARALYSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REMYELINIZATION; RETINA INJURY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; ROTAROD TEST; SPINAL CORD; TRANSMISSION ELECTRON MICROSCOPY; WESTERN BLOTTING; WHITE MATTER; WHITE MATTER VOLUME; ANIMAL; AXON; C57BL MOUSE; CENTRAL NERVOUS SYSTEM; DEMYELINATING DISEASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GENETICS; INFLAMMATION; NERVE DEGENERATION; PATHOLOGY; PHYSIOLOGY; TRANSGENIC MOUSE;

ANIMALS; AXONS; CENTRAL NERVOUS SYSTEM; DEMYELINATING DISEASES; DNA BREAKS, DOUBLE-STRANDED; DNA, MITOCHONDRIAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; INFLAMMATION; LOCOMOTION; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; NERVE DEGENERATION; OLIGODENDROGLIA;

EID: 85031909981     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.1378-17.2017     Document Type: Article

References (61)

1. Aboul-Enein F, Rauschka H, Kornek B, Stadelmann C, Stefferl A, Brück W, Lucchinetti C, Schmidbauer M, Jellinger K, Lassmann H (2003) Preferential loss of myelin-associated glycoprotein reflects hypoxia-like white matter damage in stroke and inflammatory brain diseases. J Neuropathol Exp Neurol 62:25-33. CrossRef Medline
2. Amor S, Peferoen LA, Vogel DY, Breur M, van der Valk P, Baker D, van Noort JM (2014) Inflammation in neurodegenerative diseases—an update. Immunology 142:151-166. CrossRef Medline
3. Andalib S, Talebi M, Sakhinia E, Farhoudi M, Sadeghi-Bazargani H, Motaval-lian A, Pilehvar-Soltanahmadi Y (2013) Multiple sclerosis and mitochondrial gene variations: a review. J Neurol Sci 330:10-15. CrossRef Medline
4. Axisa PP, Hafler DA (2016) Multiple sclerosis: genetics, biomarkers, treatments. Curr Opin Neurol 29:345-353. CrossRef Medline
5. Ban M, Elson J, Walton A, Turnbull D, Compston A, Chinnery P, Sawcer S (2008) Investigation of the role of mitochondrial DNA in multiple sclerosis susceptibility. PLoS One 3:e2891. CrossRef Medline
6. Barber GN (2015) STING: infection, inflammation and cancer. Nat Rev Immunol 15:760-770. CrossRef Medline
7. Brambilla R, Ashbaugh JJ, Magliozzi R, Dellarole A, Karmally S, Szymkowski DE, Bethea JR (2011) Inhibition of soluble tumour necrosis factor is therapeutic in experimental autoimmune encephalomyelitis and promotes axon preservation and remyelination. Brain 134:2736-2754. CrossRef Medline
8. Brambilla R, Dvoriantchikova G, Barakat D, Ivanov D, Bethea JR, Shesto-palov VI (2012) Transgenic inhibition of astroglial NF-κB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis. J Neuroinflammation 9:213. CrossRef Medline
9. Cabezas-Opazo FA, Vergara-Pulgar K, Pérez MJ, Jara C, Osorio-Fuentealba C, Quintanilla RA (2015) Mitochondrial dysfunction contributes to the pathogenesis of Alzheimer’s disease. Oxid Med Cell Longev 2015:509654. CrossRef Medline
10. Chandrasekaran K, Hazelton JL, Wang Y, Fiskum G, Kristian T (2006) Neuron-specific conditional expression of a mitochondrially targeted fluorescent protein in mice. J Neurosci 26:13123-13127. CrossRef Medline
11. Dendrou CA, Fugger L, Friese MA (2015) Immunopathology of multiple sclerosis. Nat Rev Immunol 15:545-558. CrossRef Medline
12. Diaz F, Thomas CK, Garcia S, Hernandez D, Moraes CT (2005) Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency. Hum Mol Genet 14:2737-2748. CrossRef Medline
13. Dutta R, McDonough J, Yin X, Peterson J, Chang A, Torres T, Gudz T, Macklin WB, Lewis DA, Fox RJ, Rudick R, Mirnics K, Trapp BD (2006) Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol 59:478-489. CrossRef Medline
14. Fischer MT, Sharma R, Lim JL, Haider L, Frischer JM, Drexhage J, Mahad D, Bradl M, van Horssen J, Lassmann H (2012) NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury. Brain 135:886-899. CrossRef Medline
15. Fukui H, Moraes CT (2009) Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging neurons. Hum Mol Genet 18: 1028-1036. CrossRef Medline
16. Fünfschilling U, Supplie LM, Mahad D, Boretius S, Saab AS, Edgar J, Brink-mann BG, Kassmann CM, Tzvetanova ID, Möbius W, Diaz F, Meijer D, Suter U, Hamprecht B, Sereda MW, Moraes CT, Frahm J, Goebbels S, Nave KA (2012) Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature 485:517-521. CrossRef Medline
17. Gualtierotti R, Guarnaccia L, Beretta M, Navone SE, Campanella R, Riboni L, Rampini P, Marfia G (2017) Modulation of neuroinflammation in the central nervous system: role of chemokines and sphingolipids. Adv Ther 34:396-420. CrossRef Medline
18. Haider L, Fischer MT, Frischer JM, Bauer J, Höftberger R, Botond G, Ester-bauer H, Binder CJ, Witztum JL, Lassmann H (2011) Oxidative damage in multiple sclerosis lesions. Brain 134:1914-1924. CrossRef Medline
19. Hämäläinen RH, Ahlqvist KJ, Ellonen P, Lepistö M, Logan A, Otonkoski T, Murphy MP, Suomalainen A (2015) mtDNA mutagenesis disrupts plu-ripotent stem cell function by altering redox signaling. Cell Rep 11:1614-1624. CrossRef Medline
20. Hudson G, Gomez-Duran A, Wilson IJ, Chinnery PF (2014) Recent mitochondrial DNA mutations increase the risk of developing common late-onset human diseases. PLoS Genet 10:e1004369. CrossRef Medline
21. Inamura N, Sugio S, Macklin WB, Tomita K, Tanaka KF, Ikenaka K (2012) Gene induction in mature oligodendrocytes with a PLP-tTA mouse line. Genesis 50:424-428. CrossRef Medline
22. Kalman B, Lublin FD, Alder H (1995) Mitochondrial DNA mutations in multiple sclerosis. Mult Scler 1:32-36. CrossRef Medline
23. Keogh MJ, Chinnery PF (2015) Mitochondrial DNA mutations in neurodegeneration. Biochim Biophys Acta 1847:1401-1411. CrossRef Medline
24. Koeppen AH, Mazurkiewicz JE (2013) Friedreich ataxia: neuropathology revised. J Neuropathol Exp Neurol 72:78-90. CrossRef Medline
25. Krysko DV, Agostinis P, Krysko O, Garg AD, Bachert C, Lambrecht BN, Vandenabeele P (2011) Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol 32:157-164. CrossRef Medline
26. Kwong JQ, Beal MF, Manfredi G (2006) The role of mitochondria in inherited neurodegenerative diseases. J Neurochem 97:1659-1675. CrossRef Medline
27. Lambertsen KL, Gramsbergen JB, Sivasaravanaparan M, Ditzel N, Sevelsted-Møller LM, Oliván-Viguera A, Rabjerg M, Wulff H, Köhler R (2012) Genetic KCa3.1-deficiency produces locomotor hyperactivity and alterations in cerebral monoamine levels. PLoS One 7:e47744. CrossRef Medline
28. Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707-717. CrossRef Medline
29. Madsen PM, Motti D, Karmally S, Szymkowski DE, Lambertsen KL, Bethea JR, Brambilla R (2016a) Oligodendroglial TNFR2 mediates membrane TNF-dependent repair in experimental autoimmune encephalomyelitis by promoting oligodendrocyte differentiation and remyelination. J Neurosci 36:5128-5143. CrossRef Medline
30. Madsen PM, Clausen BH, Degn M, Thyssen S, Kristensen LK, Svensson M, Ditzel N, Finsen B, Deierborg T, Brambilla R, Lambertsen KL (2016b) Genetic ablation of soluble tumor necrosis factor with preservation of membrane tumor necrosis factor is associated with neuroprotection after focal cerebral ischemia. J Cereb Blood Flow Metab 36:1553-1569. CrossRef Medline
31. Mahad DH, Trapp BD, Lassmann H (2015) Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 14:183-193. CrossRef Medline
32. Mahad D, Ziabreva I, Lassmann H, Turnbull D (2008) Mitochondrial defects in acute multiple sclerosis lesions. Brain 131:1722-1735. CrossRef Medline
33. Matthews L, Enzinger C, Fazekas F, Rovira A, Ciccarelli O, Dotti MT, Filippi M, Frederiksen JL, Giorgio A, Küker W, Lukas C, Rocca MA, De Stefano N, Toosy A, Yousry T, Palace J, Network M (2015) MRI in Leber’s hereditary optic neuropathy: the relationship to multiple sclerosis. J Neurol Neurosurg Psychiatry 86:537-542. CrossRef Medline
34. McTigue DM, Tripathi RB (2008) The life, death, and replacement of oligodendrocytes in the adult CNS. J Neurochem 107:1-19. CrossRef Medline
35. Nikić I, Merkler D, Sorbara C, Brinkoetter M, Kreutzfeldt M, Bareyre FM, Brück W, Bishop D, Misgeld T, Kerschensteiner M (2011) A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 17:495-499. CrossRef Medline
36. Ohl K, Tenbrock K, Kipp M (2016) Oxidative stress in multiple sclerosis: central and peripheral mode of action. Exp Neurol 277:58-67. CrossRef Medline
37. Palace J (2009) Multiple sclerosis associated with Leber’s hereditary optic neuropathy. J Neurol Sci 286:24-27. CrossRef Medline
38. Pasquini LA, Calatayud CA, Bertone Uña AL, Millet V, Pasquini JM, Soto EF (2007) The neurotoxic effect of cuprizone on oligodendrocytes depends on the presence of pro-inflammatory cytokines secreted by microglia. Neurochem Res 32:279-292. CrossRef Medline
39. Patergnani S, Fossati V, Bonora M, Giorgi C, Marchi S, Missiroli S, Rusiele-wicz T, Wieckowski MR, Pinton P (2017) Mitochondria in multiple sclerosis: molecular mechanisms of pathogenesis. Int Rev Cell Mol Biol 328:49-103. CrossRef Medline
40. Pekny M, Pekna M, Messing A, Steinhäuser C, Lee JM, Parpura V, Hol EM, Sofroniew MV, Verkhratsky A (2016) Astrocytes: a central element in neurological diseases. Acta Neuropathol 131:323-345. CrossRef Medline
41. Peterson JW, Bö L, Mörk S, Chang A, Trapp BD (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389-400. CrossRef Medline
42. Pickrell AM, Pinto M, Hida A, Moraes CT (2011) Striatal dysfunctions associated with mitochondrial DNA damage in dopaminergic neurons in a mouse model of Parkinson’s disease. J Neurosci 31:17649-17658. CrossRef Medline
43. Pinto M, Moraes CT (2015) Mechanisms linking mtDNA damage and aging. Free Radic Biol Med 85:250-258. CrossRef Medline
44. Pinto M, Pickrell AM, Wang X, Bacman SR, Yu A, Hida A, Dillon LM, Morton PD, Malek TR, Williams SL, Moraes CT (2017) Transient mitochon-drial DNA double strand breaks in mice cause accelerated aging phenotypes in a ROS-dependent but p53/p21-independent manner. Cell Death Differ 24:288-299. CrossRef Medline
45. Puckett C, Hudson L, Ono K, Friedrich V, Benecke J, Dubois-Dalcq M, Laz-zarini RA (1987) Myelin-specific proteolipid protein is expressed in myelinating Schwann cells but is not incorporated into myelin sheaths. J Neurosci Res 18:511-518. CrossRef Medline
46. Ramanathan S, Dale RC, Brilot F (2016) Anti-MOG antibody: the history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination. Autoimmun Rev 15:307-324. CrossRef Medline
47. Ryan BJ, Hoek S, Fon EA, Wade-Martins R (2015) Mitochondrial dysfunction and mitophagy in Parkinson’s: from familial to sporadic disease. Trends Biochem Sci 40:200-210. CrossRef Medline
48. Sadeghian M, Mastrolia V, Rezaei Haddad A, Mosley A, Mullali G, Schiza D, Sajic M, Hargreaves I, Heales S, Duchen MR, Smith KJ (2016) Mitochondrial dysfunction is an important cause of neurological deficits in an inflammatory model of multiple sclerosis. Sci Rep 6:33249. CrossRef Medline
49. Smith KJ, Kapoor R, Felts PA (1999) Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol 9:69-92. Medline
50. Traka M, Podojil JR, McCarthy DP, Miller SD, Popko B (2016) Oligodendrocyte death results in immune-mediated CNS demyelination. Nat Neurosci 19:65-74. CrossRef Medline
51. Trapp BD, Nave KA (2008) Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 31:247-269. CrossRef Medline
52. van Horssen J, Schreibelt G, Drexhage J, Hazes T, Dijkstra CD, van der Valk P, de Vries HE (2008) Severe oxidative damage in multiple sclerosis lesions coincides with enhanced antioxidant enzyme expression. Free Radic Biol Med 45:1729-1737. CrossRef Medline
53. Viader A, Golden JP, Baloh RH, Schmidt RE, Hunter DA, Milbrandt J (2011) Schwann cell mitochondrial metabolism supports long-term axonal survival and peripheral nerve function. J Neurosci 31:10128-10140. CrossRef Medline
54. Viader A, Sasaki Y, Kim S, Strickland A, Workman CS, Yang K, Gross RW, Milbrandt J (2013) Aberrant Schwann cell lipid metabolism linked to mitochondrial deficits leads to axon degeneration and neuropathy. Neuron 77:886-898. CrossRef Medline
55. Wang S, Jacquemyn J, Murru S, Martinelli P, Barth E, Langer T, Niessen CM, Rugarli EI (2016) The mitochondrial m-AAA protease prevents demyelination and hair greying. PLoS Genet 12:e1006463. CrossRef Medline
56. Wei X, Shao B, He Z, Ye T, Luo M, Sang Y, Liang X, Wang W, Luo S, Yang S, Zhang S, Gong C, Gou M, Deng H, Zhao Y, Yang H, Deng S, Zhao C, Yang L, Qian Z, et al (2015) Cationic nanocarriers induce cell necrosis through impairment of Na(=)/K(=)-ATPase and cause subsequent inflammatory response. Cell Res 25:237-253. CrossRef Medline
57. West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, Bestwick M, Duguay BA, Raimundo N, MacDuff DA, Kaech SM, Smiley JR, Means RE, Iwasaki A, Shadel GS (2015) Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520:553-557. CrossRef Medline
58. Witte ME, Mahad DJ, Lassmann H, van Horssen J (2014) Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis. Trends Mol Med 20:179-187. CrossRef Medline
59. Yu-Wai-Man P, Griffiths PG, Chinnery PF (2011) Mitochondrial optic neuropathies-disease mechanisms and therapeutic strategies. Prog Retin Eye Res 30:81-114. CrossRef Medline
60. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104-107. CrossRef Medline
61. Ziabreva I, Campbell G, Rist J, Zambonin J, Rorbach J, Wydro MM, Lassmann H, Franklin RJ, Mahad D (2010) Injury and differentiation following inhibition of mitochondrial respiratory chain complex IV in rat oligodendrocytes. Glia 58:1827-1837. CrossRef Medline