Complement receptor 2 is up regulated in the spinal cord following nerve root injury and modulates the spinal cord response

Journal of Neuroinflammation

Fredrik Piehl⁵  Staffan Cullheim³  Margarita Diez⁵  Kristina Nilsson Ekdahl⁴  Bo Nilsson⁴  Norbert Hübner²  Karin Harnesk⁵  Johan Zelano³  Matthias Heinig²  Nada Abdelmagid⁵  Faiez Al Nimer⁵  Cecilia A. Dominguez⁵  Shahin Aeinehband⁵  Mikael Ström⁵  Alexander Berg³  Rickard P. F. Lindblom¹ 

[1] Neuroimmunology Unit L8:04 CMM, Karolinska University Hospital, Stockholm, 171 76, Sweden;Experimental Genetics of Cardiovascular Diseases, Max-Delbrück Center for Molecular Medicine, Berlin, Germany;Department of Neuroscience, Division of Neuronal Regeneration, Karolinska Institutet, Stockholm, Sweden;Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden;Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden

关键词: Synapses;    Neurodegeneration;    Neuroinflammation;    Complement receptor 2;    Complement system;   

Others  :  1231685
DOI  :  10.1186/s12974-015-0413-6

 received in 2015-08-01, accepted in 2015-10-16,  发布年份 2015

【 摘 要 】

Background

Activation of the complement system has been implicated in both acute and chronic states of neurodegeneration. However, a detailed understanding of this complex network of interacting components is still lacking.

Methods

Large-scale global expression profiling in a rat F2(DAxPVG) intercross identified a strong cis-regulatory influence on the local expression of complement receptor 2 (Cr2) in the spinal cord after ventral root avulsion (VRA). Expression of Cr2 in the spinal cord was studied in a separate cohort of DA and PVG rats at different time-points after VRA, and also following sciatic nerve transection (SNT) in the same strains. Consequently, Cr2 ^−/− mice and Wt controls were used to further explore the role of Cr2 in the spinal cord following SNT. The in vivo experiments were complemented by astrocyte and microglia cell cultures.

Results

Expression of Cr2 in naïve spinal cord was low but strongly up regulated at 5–7 days after both VRA and SNT. Levels of Cr2 expression, as well as astrocyte activation, was higher in PVG rats than DA rats following both VRA and SNT. Subsequent in vitro studies proposed astrocytes as the main source of Cr2 expression. A functional role for Cr2 is suggested by the finding that transgenic mice lacking Cr2 displayed increased loss of synaptic nerve terminals following nerve injury. We also detected increased levels of soluble CR2 (sCR2) in the cerebrospinal fluid of rats following VRA.

Conclusions

These results demonstrate that local expression of Cr2 in the central nervous system is part of the axotomy reaction and is suggested to modulate subsequent complement mediated effects.

【 授权许可】

   
2015 Lindblom et al.

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