Interferon (IFN) beta treatment induces major histocompatibility complex (MHC) class I expression in the spinal cord and enhances axonal growth and motor function recovery following sciatic nerve crush in mice.
OBJECTIVE
Major histocompatibility complex (MHC) class I expression by neurones and glia constitutes an important pathway that regulates synaptic plasticity. The upregulation of MHC class I after treatment with interferon beta (IFN beta) accelerates the response to injury. Therefore the present work studied the regenerative outcome after peripheral nerve lesion and treatment with IFN beta, aiming at increasing MHC class I upregulation in the spinal cord.


METHODS
C57BL/6J mice were subjected to unilateral sciatic nerve crush and treatment with IFN beta. The lumbar spinal cords were processed for immunohistochemistry, in situ hybridization, Western blotting and RT-PCR, while the sciatic nerves were submitted for immunohistochemistry, morphometry and counting of regenerated axons. Motor function recovery was monitored using the walking track test.


RESULTS
Increased MHC class I expression in the motor nucleus of IFN beta-treated animals was detected. In the peripheral nerve, IFN beta-treated animals showed increased S100, GAP-43 and p75NTR labelling coupled with a significantly greater number of regenerated axons. No significant differences were found in neurofilament or laminin labelling. The morphological findings, indicating improvements in the regenerative process after IFN treatment were in line with the motor behaviour test applied to the animals during the recovery process.


CONCLUSIONS
The present data reinforce the role of MHC class I upregulation in the response to injury, and suggest that IFN treatment may be beneficial to motor recovery after axotomy.
Zanon
R G
RG
Laboratory of Nerve Regeneration, Department of Anatomy, Institute of Biology Laboratory of experimental gastroenterology, Department of Internal Medicine, University of Campinas, Campinas, Brazil.
Cartarozzi
L P
LP
Victório
S C S
SC
Moraes
J C
JC
Morari
J
J
Velloso
L A
LA
Oliveira
A L R
AL
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000187:drug effects; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology*; D017403:In Situ Hybridization; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D020127:Recovery of Function / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000648:ultrastructure; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D007155:Immunologic Factors; D012333:RNA, Messenger; D016899:Interferon-beta