Ablation of Proliferating Cells in the CNS Exacerbates Motor Neuron Disease Caused by Mutant Superoxide Dismutase

被引:17
作者
Audet, Jean-Nicolas [1 ]
Gowing, Genevieve [1 ]
Paradis, Renee [1 ]
Soucy, Genevieve [1 ]
Julien, Jean-Pierre [1 ]
机构
[1] Univ Laval, CHUQ, Res Ctr, Dept Psychiat & Neurosci, Quebec City, PQ, Canada
来源
PLOS ONE | 2012年 / 7卷 / 04期
关键词
GROWTH-FACTOR-I; MOUSE MODEL; EXTEND SURVIVAL; ANIMAL-MODEL; SPINAL-CORD; MICROGLIA; IGF-1; PROGRESSION; ASTROCYTES; SOD1;
D O I
10.1371/journal.pone.0034932
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Proliferation of glia and immune cells is a common pathological feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Here, to investigate the role of proliferating cells in motor neuron disease, SOD1(G93A) transgenic mice were treated intracerebroventicularly (ICV) with the anti-mitotic drug cytosine arabinoside (Ara-C). ICV delivery of Ara-C accelerated disease progression in SOD1(G93A) mouse model of ALS. Ara-C treatment caused substantial decreases in the number of microglia, NG2+ progenitors, Olig2+ cells and CD3+ T cells in the lumbar spinal cord of symptomatic SOD1(G93A) transgenic mice. Exacerbation of disease was also associated with significant alterations in the expression inflammatory molecules IL-1 beta, IL-6, TGF-beta and the growth factor IGF-1.
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页数:7
相关论文
共 38 条
[11]   Intraspinal cord delivery of IGF-I mediated by adeno-associated virus 2 is neuroprotective in a rat model of familial ALS [J].
Franz, Colin K. ;
Federici, Thais ;
Yang, Jun ;
Backus, Carey ;
Oh, Sang Su ;
Teng, Qingshan ;
Carlton, Erin ;
Bishop, Kathie M. ;
Gasmi, Mehdi ;
Bartus, Raymond T. ;
Feldman, Eva L. ;
Boulis, Nicholas M. .
NEUROBIOLOGY OF DISEASE, 2009, 33 (03) :473-481
[12]   Ablation of Proliferating Microglia Does Not Affect Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis Caused by Mutant Superoxide Dismutase [J].
Gowing, Genevieve ;
Philips, Thomas ;
Van Wijmeersch, Bart ;
Audet, Jean-Nicolas ;
Dewil, Maarten ;
Van Den Bosch, Ludo ;
Billiau, An D. ;
Robberecht, Wim ;
Julien, Jean-Pierre .
JOURNAL OF NEUROSCIENCE, 2008, 28 (41) :10234-10244
[13]   Macrophage colony stimulating factor (M-CSF) exacerbates ALS disease in a mouse model through altered responses of microglia expressing mutant superoxide dismutase [J].
Gowing, Genevieve ;
Lalancette-Hebert, Melanie ;
Audet, Jean-Nicolas ;
Dequen, Florence ;
Julien, Jean-Pierre .
EXPERIMENTAL NEUROLOGY, 2009, 220 (02) :267-275
[14]   Microglia in ALS: The Good, The Bad, and The Resting [J].
Henkel, Jenny S. ;
Beers, David R. ;
Zhao, Weihua ;
Appel, Stanley H. .
JOURNAL OF NEUROIMMUNE PHARMACOLOGY, 2009, 4 (04) :389-398
[15]   Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond [J].
Ilieva, Hristelina ;
Polymenidou, Magdalini ;
Cleveland, Don W. .
JOURNAL OF CELL BIOLOGY, 2009, 187 (06) :761-772
[16]   Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model [J].
Kaspar, BK ;
Lladó, J ;
Sherkat, N ;
Rothstein, JD ;
Gage, FH .
SCIENCE, 2003, 301 (5634) :839-842
[17]  
Katsuno M, 2011, Curr Mol Med, V11, P48, DOI 10.2174/156652411794474356
[18]   Glial Cells in Amyotrophic Lateral Sclerosis [J].
Lasiene, Jurate ;
Yamanaka, Koji .
NEUROLOGY RESEARCH INTERNATIONAL, 2011, 2011
[19]   Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease [J].
Lepore, Angelo C. ;
Rauck, Britta ;
Dejea, Christine ;
Pardo, Andrea C. ;
Rao, Mahendra S. ;
Rothstein, Jeffrey D. ;
Maragakis, Nicholas J. .
NATURE NEUROSCIENCE, 2008, 11 (11) :1294-1301
[20]   Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS [J].
Lepore, Angelo C. ;
Haenggeli, Christine ;
Gasmi, Mehdi ;
Bishop, Kathie M. ;
Bartus, Raymond T. ;
Maragakis, Nicholas J. ;
Rothstein, Jeffrey D. .
BRAIN RESEARCH, 2007, 1185 :256-265