Distinct Changes in Synaptic Protein Composition at Neuromuscular Junctions of Extraocular Muscles versus Limb Muscles of ALS Donors

被引:16
作者
Liu, Jing-Xia [1 ]
Brannstrom, Thomas [2 ]
Andersen, Peter M. [3 ]
Pedrosa-Domellof, Fatima [1 ,4 ]
机构
[1] Umea Univ, Sect Anat, Dept Integrat Med Biol, Umea, Sweden
[2] Umea Univ, Dept Med Biosci, Umea, Sweden
[3] Umea Univ, Dept Pharmacol & Clin Neuroscience, Umea, Sweden
[4] Umea Univ, Dept Clin Sci, Umea, Sweden
来源
PLOS ONE | 2013年 / 8卷 / 02期
基金
瑞典研究理事会;
关键词
AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURONS; SUPEROXIDE-DISMUTASE; NEUROFILAMENT LIGHT; CEREBROSPINAL-FLUID; NERVOUS-SYSTEM; SPINAL-CORD; DISEASE; P75(NTR); EXPRESSION;
D O I
10.1371/journal.pone.0057473
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
The pathophysiology of amyotrophic lateral sclerosis (ALS) is very complex and still rather elusive but in recent years evidence of early involvement of the neuromuscular junctions (NMJs) has accumulated. We have recently reported that the human extraocular muscles (EOMs) are far less affected than limb muscles at the end-stage of ALS from the same donor. The present study aimed to compare the differences in synaptic protein composition at NMJ and in nerve fibers between EOM and limb muscles from ALS donors and controls. Neurofilament light subunit and synaptophysin decreased significantly at NMJs and in nerve fibers in limb muscles with ALS whereas they were maintained in ALS EOMs. S100B was significantly decreased at NMJs and in nerve fibers in both EOMs and limb muscles of ALS donors, but other markers confirmed the presence of terminal Schwann cells in these NMJs. p75 neurotrophin receptor was present in nerve fibers but absent at NMJs in ALS limb muscles. The EOMs were able to maintain the integrity of their NMJs to a very large extent until the end-stage of ALS, in contrast to the limb muscles. Changes in Ca2+ homeostasis, reflected by altered S100B distribution, might be involved in the breakdown of nerve-muscle contact at NMJs in ALS.
引用
收藏
页数:12
相关论文
共 38 条
[21]   Neuromuscular junction in health and disease [J].
Hirsch, N. P. .
BRITISH JOURNAL OF ANAESTHESIA, 2007, 99 (01) :132-138
[22]   The origin and development of glial cells in peripheral nerves [J].
Jessen, KR ;
Mirsky, R .
NATURE REVIEWS NEUROSCIENCE, 2005, 6 (09) :671-682
[23]   Neurofilament functions in health and disease [J].
Julien, JP .
CURRENT OPINION IN NEUROBIOLOGY, 1999, 9 (05) :554-560
[24]   Corticospinal tract degeneration and possible pathogenesis in ALS evaluated by MR diffusion tensor imaging [J].
Karlsborg, M ;
Rosenbaum, S ;
Wiegell, MR ;
Simonsen, H ;
Larsson, HBW ;
Werdelin, LM ;
Gredal, O .
AMYOTROPHIC LATERAL SCLEROSIS, 2004, 5 (03) :136-140
[25]   Overexpression of neurofilament subunit NF-L and NF-H extends survival of a mouse model for amyotrophic lateral sclerosis [J].
Kong, JM ;
Xu, ZS .
NEUROSCIENCE LETTERS, 2000, 281 (01) :72-74
[26]   Different Impact of ALS on Laminin Isoforms in Human Extraocular Muscles versus Limb Muscles [J].
Liu, Jing-Xia ;
Brannstrom, Thomas ;
Andersen, Peter M. ;
Pedrosa-Domellof, Fatima .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2011, 52 (07) :4842-4852
[27]  
LUPA MT, 1989, J NEUROSCI, V9, P3937
[28]   Selective loss of neurofilament expression in Cu/Zn superoxide dismutase (SOD1) linked amyotrophic lateral sclerosis [J].
Menzies, FM ;
Grierson, AJ ;
Cookson, MR ;
Heath, PR ;
Tomkins, J ;
Figlewicz, DA ;
Ince, PG ;
Shaw, PJ .
JOURNAL OF NEUROCHEMISTRY, 2002, 82 (05) :1118-1128
[29]   S-100β protein is upregulated in astrocytes and motor neurons in the spinal cord of patients with amyotrophic lateral sclerosis [J].
Migheli, A ;
Cordera, S ;
Bendotti, C ;
Atzori, C ;
Piva, R ;
Schiffer, D .
NEUROSCIENCE LETTERS, 1999, 261 (1-2) :25-28