期刊
EXPERIMENTAL NEUROLOGY
卷 237, 期 1, 页码 8-17出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2012.06.008
关键词
Complement proteins; Synaptic plasticity; Motoneuron; Peripheral nerve lesion
资金
- Swedish Research Council [6815, 20116, 11548]
- ALF Goteborg [11267, 11392]
- AFA Research Foundation
- Sten A. Olsson Foundation for Research and Culture
- Nano Net COST Action
- EU FP 7 Programs EduGlia [237956]
- TargetBraIn [279017]
- Brain Foundation
- Marianne and Marcus Wallenberg Foundation
- Friends of Karolinska Institutet
- Karolinska Institutet
- J. and B. Wennerstrom's Foundations for Neurological Research
- AFA
- STENA
- R. and T. Soderberg's foundation
- E. Jacobson's foundation
- W. and M. Lundgren's foundation
- R. and U. Amlov's foundation
- Swiss National Science Foundation fellowship
Complement proteins C1q and C3 play a critical role in synaptic elimination during development. Axotomy of spinal motoneurons triggers removal of synaptic terminals from the cell surface of motoneurons by largely unknown mechanisms. We therefore hypothesized that the complement system is involved also in synaptic stripping of injured motoneurons. In the sciatic motor pool of wild type (WT) mice, the immunoreactivity (IR) for both C1q and C3 was increased after sciatic nerve transection (SNT). Mice deficient in C3 (C3(-/-)) showed a reduced loss of synaptic terminals from injured motoneurons at one week after SNT, as assessed by immunoreactivity for synaptic markers and electron microscopy. In particular, the removal of putative inhibitory terminals, immunopositive for vesicular inhibitory amino acid transporter (VIAAT) and ultrastructurally identified as type F synapses, was reduced in C3(-/-) mice. In contrast, lesion-induced removal of nerve terminals in C1q(-/-) mice appeared similar to WT mice. Growth associated protein (GAP)-43 mRNA expression in lesioned motoneurons increased much more in C3(-/-) compared to WT mice after SNT. After sciatic nerve crush (SNC), the C3(-/-) mice showed a faster functional recovery, assessed as grip strength, compared to WT mice. No differences were detected regarding nerve inflammation at the site of injury or pattern of muscle reinnervation. These data indicate that a non-classical pathway of complement activation is involved in axotomy-induced adult synapse removal, and that its inhibition promotes functional recovery. (c) 2012 Elsevier Inc. All rights reserved.
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