α-syn suppression reverses synaptic and memory defects in a mouse model of dementia with lewy bodies

Journal of Neuroscience

Volumn 31, Issue 27, 2011, Pages 10076-10087

  Lim, Youngshin ^a   Kehm, Victoria M ^a   Lee, Edward B ^a   Soper, James H ^a   Li, Chi ^a   Trojanowski, John Q ^a   Lee, Virginia M Y ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOACCUMULATION; CONTROLLED STUDY; DEMENTIA; ELECTROENCEPHALOGRAM; ENZYME REPRESSION; FEMALE; HIPPOCAMPUS; LEWY BODY; LIMBIC SYSTEM; MALE; MEMORY; MEMORY DISORDER; MOUSE; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; SYNAPTIC TRANSMISSION;

ACOUSTIC STIMULATION; AGE FACTORS; ALPHA-SYNUCLEIN; ANALYSIS OF VARIANCE; ANIMALS; ANIMALS, NEWBORN; BRAIN; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 2; CONDITIONING, CLASSICAL; CUES; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; EMBRYO, MAMMALIAN; FEAR; FEMALE; GENE EXPRESSION REGULATION; GLIAL FIBRILLARY ACIDIC PROTEIN; GLIOSIS; HUMANS; INDOLES; LEWY BODY DISEASE; MALE; MEMORY DISORDERS; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MUTATION; NERVE DEGENERATION; NERVE TISSUE PROTEINS; SERINE; SYNAPSES;

EID: 79960069979     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.0618-11.2011     Document Type: Article

References (51)

1. Aarsland D, Beyer MK, Kurz MW (2008) Dementia in Parkinson's disease. Curr Opin Neurol 21:676-682.
2. Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VMY, Trojanowski JQ, Iwatsubo T (1998) Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. AmJ Pathol 152:879-884.
3. Burré J, Sharma M, Tsetsenis T, Buchman V, Etherton MR, Südhof TC (2010) Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329:1663-1667.
4. Chen L, Feany MB (2005) Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci 8:657-663.
5. Chung CY, Koprich JB, Siddiqi H, Isacson O (2009) Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathy. J Neurosci 29:3365-3373.
6. Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ, Bhullar B, Liu K, Xu K, Strathearn KE, Liu F, Cao S, Caldwell KA, Caldwell GA, Marsischky G, Kolodner RD, Labaer J, Rochet JC, Bonini NM, Lindquist S (2006) Alpha-Synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313:324-328.
7. Duda JE, Giasson BI, Mabon ME, Lee VM, Trojanowski JQ (2002a) Novel antibodies to synuclein show abundant striatal pathology in Lewy body diseases. Ann Neurol 52:205-210.
8. Duda JE, Giasson BI, Mabon ME, Miller DC, Golbe LI, Lee VM, Trojanowski JQ (2002b) Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred. Acta Neuropathol 104:7-11.
9. Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K, Iwatsubo T (2002) Alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4:160-164.
10. Garcia-Reitböck P, Anichtchik O, Bellucci A, Iovino M, Ballini C, Fineberg E, Ghetti B, Della Corte L, Spano P, Tofaris GK, Goedert M, Spillantini MG (2010) SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease. Brain 133:2032-2044.
11. Giasson BI, Duda JE, Quinn SM, Zhang B, Trojanowski JQ, Lee VM (2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34:521-533.
12. Goldmann Gross R, Siderowf A, Hurtig HI (2008) Cognitive impairment in Parkinson's disease and dementia with Lewy bodies: a spectrum of disease. Neurosignals 16:24-34.
13. Gómez-Tortosa E, Newell K, Irizarry MC, Sanders JL, Hyman BT (2000) Alpha-synuclein immunoreactivity in dementia with Lewy bodies: morphological staging and comparison with ubiquitin immunostaining. Acta Neuropathol 99:352-357.
14. Hanson JC, Lippa CF (2009) Lewy body dementia. Int Rev Neurobiol 84:215-228.
15. Ikeuchi T, Kakita A, Shiga A, Kasuga K, Kaneko H, Tan CF, Idezuka J, Wakabayashi K, Onodera O, Iwatsubo T, Nishizawa M, Takahashi H, Ishikawa A (2008) Patients homozygous and heterozygous for SNCA duplication in a family with parkinsonism and dementia. Arch Neurol 65:514-519.
16. Jankowsky JL, Slunt HH, Gonzales V, Savonenko AV, Wen JC, Jenkins NA, Copeland NG, Younkin LH, Lester HA, Younkin SG, Borchelt DR (2005) Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease. PLoS Med 2:e355.
17. Jellinger KA (2004) Lewy body-related alpha-synucleinopathy in the aged human brain. J Neural Transm 111:1219-1235.
18. Kahle PJ, Neumann M, Ozmen L, Muller V, Jacobsen H, Spooren W, Fuss B, Mallon B, Macklin WB, Fujiwara H, Hasegawa M, Iwatsubo T, Kretzschmar HA, Haass C (2002) Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes. EMBO Rep 3:583-588.
19. Kim JJ, Fanselow MS (1992) Modality-specific retrograde-amnesia of fear. Science 256:675-677.
20. Kotzbauer PT, Giasson BI, Kravitz AV, Golbe LI, Mark MH, Trojanowski JQ, Lee VM (2004) Fibrillization of alpha-synuclein and tau in familial Parkinson's disease caused by the A53T alpha-synuclein mutation. Exp Neurol 187:279-288.
21. Kramer ML, Schulz-Schaeffer WJ (2007) Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci 27:1405-1410.
22. Kuwahara T, Koyama A, Koyama S, Yoshina S, Ren CH, Kato T, Mitani S, Iwatsubo T (2008) A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in alpha-synuclein transgenic C. elegans. Hum Mol Genet 17:2997-3009.
23. Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y (1988) Lewy bodies are ubiquitinated-a light and electron-microscopic immunocytochemical study. Acta Neuropathol 75:345-353.
24. Larsen KE, Schmitz Y, Troyer MD, Mosharov E, Dietrich P, Quazi AZ, Savalle M, Nemani V, Chaudhry FA, Edwards RH, Stefanis L, Sulzer D (2006) Alpha-Synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. J Neurosci 26:11915-11922.
25. Lennox G, Lowe J, Morrell K, Landon M, Mayer RJ (1989) Anti-ubiquitin immunocytochemistry is more sensitive than conventional techniques in the detection of diffuse Lewy body disease. J Neurol Neurosurg Psychiatry 52:67-71.
26. Lim Y, Kehm VM, Li C, Trojanowski JQ, Lee VM (2010) Forebrain overexpression of alpha-synuclein leads to early postnatal hippocampal neuron loss and synaptic disruption. Exp Neurol 221:86-97.
27. Love S, Nicoll JA (1992) Comparison of modified Bielschowsky silver impregnation and antiubiquitin immunostaining of cortical and nigral Lewy bodies. Neuropathol Appl Neurobiol 18:585-592.
28. Mayford M, Bach ME, Huang YY, Wang L, Hawkins RD, Kandel ER (1996) Control of memory formation through regulated expression of a CaMKII transgene. Science 274:1678-1683.
29. McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, et al. (2005) Diagnosis and management of dementia with Lewy bodies-third report of the DLB Consortium. Neurology 65:1863-1872.
30. Mikolaenko I, Pletnikova O, Kawas CH, O'Brien R, Resnick SM, Crain B, Troncoso JC (2005) Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA). J Neuropathol Exp Neurol 64:156-162.
31. Nemani VM, Lu W, Berge V, Nakamura K, Onoa B, Lee MK, Chaudhry FA, Nicoll RA, Edwards RH (2010) Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65:66-79.
32. Nuber S, Petrasch-Parwez E, Winner B, Winkler J, von Hörsten S, Schmidt T, Boy J, Kuhn M, Nguyen HP, Teismann P, Schulz JB, Neumann M, Pichler BJ, Reischl G, Holzmann C, Schmitt I, Bornemann A, Kuhn W, Zimmermann F, Servadio A, et al. (2008) Neurodegeneration and motor dysfunction in a conditional model of Parkinson's disease. J Neurosci 28:2471-2484.
33. Ohara K, Takauchi S, Kokai M, Morimura Y, Nakajima T, Morita Y (1999) Familial dementia with Lewy bodies (DLB). Clin Neuropathol 18:232-239.
34. Paleologou KE, Schmid AW, Rospigliosi CC, Kim HY, Lamberto GR, Fredenburg RA, Lansbury PT Jr, Fernandez CO, Eliezer D, Zweckstetter M, Lashuel HA (2008) Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of alpha-synuclein. J Biol Chem 283:16895-16905.
35. Parkkinen L, Soininen H, Alafuzoff I (2003) Regional distribution of alphasynuclein pathology in unimpaired aging and Alzheimer disease. J Neuropath Exp Neurol 62:363-367.
36. Paxinos G, Franklin KBJ (2011) The mouse brain in stereotaxic coordinates. San Diego: Academic.
37. Sampathu DM, Giasson BI, Pawlyk AC, Trojanowski JQ, Lee VM (2003) Ubiquitination of alpha-synuclein is not required for formation of pathological inclusions in alpha-synucleinopathies. Am J Pathol 163:91-100.
38. Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E, Forster C, Yue M, Orne J, Janus C, Mariash A, Kuskowski M, Hyman B, Hutton M, Ashe KH (2005) Tau suppression in a neurodegenerative mouse model improves memory function. Science 309:476-481.
39. Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C, Kubo M, Kawaguchi T, Tsunoda T, Watanabe M, Takeda A, Tomiyama H, Nakashima K, Hasegawa K, Obata F, Yoshikawa T, Kawakami H, Sakoda S, Yamamoto M, Hattori N, Murata M, et al. (2009) Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat Genet 41:1303-1307.
40. Scott DA, Tabarean I, Tang Y, Cartier A, Masliah E, Roy S (2010) A pathologic cascade leading to synaptic dysfunction in alpha-synuclein-induced neurodegeneration. J Neurosci 30:8083-8095.
41. Seidel K, Schöls L, Nuber S, Petrasch-Parwez E, Gierga K, Wszolek Z, Dickson D, Gai WP, Bornemann A, Riess O, Rami A, Den Dunnen WF, Deller T, Rüb U, Krüger R (2010) First appraisal of brain pathology owing to A30P mutant alpha-synuclein. Ann Neurol 67:684-689.
42. Simón-Sánchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, Paisan-Ruiz C, Lichtner P, Scholz SW, Hernandez DG, Krüger R, Federoff M, Klein C, Goate A, Perlmutter J, Bonin M, Nalls MA, Illig T, Gieger C, Houlden H, et al. (2009) Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat Genet 41:1308-1312.
43. Soper JH, Roy S, Stieber A, Lee E, Wilson RB, Trojanowski JQ, Burd CG, Lee VM (2008) Alpha-Synuclein-induced aggregation of cytoplasmic vesicles in Saccharomyces cerevisiae. Mol Biol Cell 19:1093-1103.
44. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839-840.
45. Spira PJ, Sharpe DM, Halliday G, Cavanagh J, Nicholson GA (2001) Clinical and pathological features of a parkinsonian syndrome in a family with an Ala53Thr alpha-synuclein mutation. Ann Neurol 49:313-319.
46. Thayanidhi N, Helm JR, Nycz DC, Bentley M, Liang Y, Hay JC (2010) Alpha-Synuclein delays endoplasmic reticulum (ER)-to-Golgi transport in mammalian cells by antagonizing ER/Golgi SNAREs. Mol Biol Cell 21:1850-1863.
47. Tremblay P, Meiner Z, Galou M, Heinrich C, Petromilli C, Lisse T, Cayetano J, Torchia M, Mobley W, Bujard H, DeArmond SJ, Prusiner SB (1998) Doxycycline control of prion protein transgene expression modulates prion disease in mice. Proc Natl Acad Sci U S A 95:12580-12585.
48. van Ham TJ, Thijssen KL, Breitling R, Hofstra RM, Plasterk RH, Nollen EA (2008) C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging. PLoS Genet 4:e100027.
49. Waxman EA, Giasson BI (2008) Specificity and regulation of casein kinasemediated phosphorylation of alpha-synuclein. J Neuropathol Exp Neurol 67:402-416.
50. Zaccai J, McCracken C, Brayne C (2005) A systematic review of prevalence and incidence studies of dementia with Lewy bodies. Age Ageing 34: 561-566.
51. Zhang B, Veasey SC, Wood MA, Leng LZ, Kaminski C, Leight S, Abel T, Lee VM, Trojanowski JQ (2005) Impaired rapid eye movement sleep in the Tg2576 APP murine model of Alzheimer's disease with injury to pedunculopontine cholinergic neurons. Am J Pathol 167:1361-1369.