Mice lacking protease nexin-1 show delayed structural and functional recovery after sciatic nerve crush

Lino, Maria Maddalena and Atanasoski, Suzana and Kvajo, Mirna and Fayard, Bérengère and Moreno, Eliza and Brenner, Hans Rudolf and Suter, Ueli and Monard, Denis. (2007) Mice lacking protease nexin-1 show delayed structural and functional recovery after sciatic nerve crush. Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 27, H. 14. pp. 3677-3685.

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Official URL: http://edoc.unibas.ch/dok/A6212159

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Multiple molecular mechanisms influence nerve regeneration. Because serine proteases were shown to affect peripheral nerve regeneration, we performed nerve crush experiments to study synapse reinnervation in adult mice lacking the serpin protease nexin-1 (PN-1). PN-1 is a potent endogenous inhibitor of thrombin, trypsin, tissue plasminogen activators (tPAs), and urokinase plasminogen activators. Compared with the wild type, a significant delay in synapse reinnervation was detected in PN-1 knock-out (KO) animals, which was associated with both reduced proliferation and increased apoptosis of Schwann cells. Various factors known to affect Schwann cells were also altered. Fibrin deposits, tPA activity, mature BDNF, and the low-affinity p75 neurotrophin receptor were increased in injured sciatic nerves of mutant mice. To test whether the absence of PN-1 in Schwann cells or in the axon caused delay in reinnervation, PN-1 was overexpressed exclusively in the nerves of PN-1 KO mice. Neuronal PN-1 expression did not rescue the delayed reinnervation. The results suggest that Schwann cell-derived PN-1 is crucial for proper reinnervation through its contribution to the autocrine control of proliferation and survival. Thus, the precise balance between distinct proteases and serpins such as PN-1 can modulate the overall impact on the kinetics of recovery.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Cellular Neurobiology (Atanasoski)
UniBasel Contributors:Atanasoski, Suzana
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Society for Neuroscience
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Dec 2015 10:54
Deposited On:31 Jan 2014 09:50

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