Characterization of Lewy Body Pathology in 12-and 16-Year-Old Intrastriatal Mesencephalic Grafts Surviving in a Patient With Parkinson's Disease

被引:158
作者
Li, Jia-Yi [1 ]
Englund, Elisabet [2 ]
Widner, Hakan [3 ]
Rehncrona, Stig
Bjorklund, Anders [4 ]
Lindvall, Olle [3 ,5 ]
Brundin, Patrik [1 ]
机构
[1] Lund Univ, Neuronal Survival Unit, Wallenberg Neurosci Ctr, S-22184 Lund, Sweden
[2] Lund Univ, Dept Neuropathol, S-22184 Lund, Sweden
[3] Lund Univ, Dept Clin Sci, Div Neurol, S-22184 Lund, Sweden
[4] Lund Univ, Neurobiol Unit, Wallenberg Neurosci Ctr, S-22184 Lund, Sweden
[5] Lund Univ, Sect Restorat Neurol, Wallenberg Neurosci Ctr, S-22184 Lund, Sweden
基金
瑞典研究理事会;
关键词
neural transplantation; Lewy body; protein aggregation; alpha-synuclein; transmissible neurological disease; ALPHA-SYNUCLEIN; NIGRAL TRANSPLANTS; CELL; NEURONS; BRAIN; TRANSMISSION; PROPAGATION; BIOLOGY;
D O I
10.1002/mds.23012
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We previously reported the occurrence of Lewy bodies in grafted human fetal mesencephalic neurons in two patients with Parkinson's disease. Here, we have used immunohistochemistry and electron microscopy to characterize the development of Lewy bodies in one of these cases. This patient was operated in putamen on both sides at 12 or 16 years before death, respectively. We demonstrate that 2% of the 12-year-old and 5% of the 16-year-old grafted, presumed dopaminergic neurons contained Lewy bodies immunoreactive for alpha-synuclein. Based on morphological analysis, two forms of alpha-synuclein-positive aggregates were distinguished in the grafts, the first a classical and compact Lewy body, the other a loose meshwork aggregate. Lewy bodies in the grafts stained positively for ubiquitin and thioflavin-S, and contained characteristic re-synuclein immunoreactive electron dense fibrillar structures on electron microscopy. Our data indicate that Lewy bodies develop gradually in transplanted dopaminergic neurons in a fashion similar to that in dopaminergic neurons in the host substantia nigra. (C) 2010 Movement Disorder Society
引用
收藏
页码:1091 / 1096
页数:6
相关论文
共 24 条
[1]   CELL BIOLOGY Beyond the prion principle [J].
Aguzzi, Adriano .
NATURE, 2009, 459 (7249) :924-925
[2]   Staging/typing of Lewy body related α-synuclein pathology: a study of the BrainNet Europe Consortium [J].
Alafuzoff, Irina ;
Ince, Paul G. ;
Arzberger, Thomas ;
Al-Sarraj, Safa ;
Bell, Jeanne ;
Bodi, Istvan ;
Bogdanovic, Nenad ;
Bugiani, Orso ;
Ferrer, Isidro ;
Gelpi, Ellen ;
Gentleman, Stephen ;
Giaccone, Giorgio ;
Ironside, James W. ;
Kavantzas, Nikolaos ;
King, Andrew ;
Korkolopoulou, Penelope ;
Kovacs, Gabor G. ;
Meyronet, David ;
Monoranu, Camelia ;
Parchi, Piero ;
Parkkinen, Laura ;
Patsouris, Efstratios ;
Roggendorf, Wolfgang ;
Rozemuller, Annemieke ;
Stadelmann-Nessler, Christine ;
Streichenberger, Nathalie ;
Thal, Dietmar R. ;
Kretzschmar, Hans .
ACTA NEUROPATHOLOGICA, 2009, 117 (06) :635-652
[3]   Staging of brain pathology related to sporadic Parkinson's disease [J].
Braak, H ;
Del Tredici, K ;
Rüb, U ;
de Vos, RAI ;
Steur, ENHJ ;
Braak, E .
NEUROBIOLOGY OF AGING, 2003, 24 (02) :197-211
[4]   Research in motion: the enigma of Parkinson's disease pathology spread [J].
Brundin, Patrik ;
Li, Jia-Yi ;
Holton, Janice L. ;
Lindvall, Olle ;
Revesz, Tamas .
NATURE REVIEWS NEUROSCIENCE, 2008, 9 (10) :741-745
[5]   Age-associated increases of α-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion:: Is this the target for Parkinson's disease? [J].
Chu, Yaping ;
Kordower, Jeffrey H. .
NEUROBIOLOGY OF DISEASE, 2007, 25 (01) :134-149
[6]   Transmission and spreading of tauopathy in transgenic mouse brain [J].
Clavaguera, Florence ;
Bolmont, Tristan ;
Crowther, R. Anthony ;
Abramowski, Dorothee ;
Frank, Stephan ;
Probst, Alphonse ;
Fraser, Graham ;
Stalder, Anna K. ;
Beibel, Martin ;
Staufenbiel, Matthias ;
Jucker, Mathias ;
Goedert, Michel ;
Tolnay, Markus .
NATURE CELL BIOLOGY, 2009, 11 (07) :909-U325
[7]   Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein [J].
Desplats, Paula ;
Lee, He-Jin ;
Bae, Eun-Jin ;
Patrick, Christina ;
Rockenstein, Edward ;
Crews, Leslie ;
Spencer, Brian ;
Masliah, Eliezer ;
Lee, Seung-Jae .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (31) :13010-13015
[8]   The comparative biology of neuromelanin and lipofuscin in the human brain [J].
Double, K. L. ;
Dedov, V. N. ;
Fedorow, H. ;
Kettle, E. ;
Halliday, G. M. ;
Garner, B. ;
Brunk, U. T. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2008, 65 (11) :1669-1682
[9]   Propagation of Tau Misfolding from the Outside to the Inside of a Cell [J].
Frost, Bess ;
Jacks, Rachel L. ;
Diamond, Marc I. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (19) :12845-12852
[10]   A stable proportion of Lewy body bearing neurons in the substantia nigra suggests a model in which the Lewy body causes neuronal death [J].
Greffard, Sandrine ;
Verny, Marc ;
Bonnet, Anne-Marie ;
Seilhean, Danielle ;
Hauw, Jean-Jacques ;
Duyckaerts, Charles .
NEUROBIOLOGY OF AGING, 2010, 31 (01) :99-103