Major histocompatibility complex class I expression and glial reaction influence spinal motoneuron synaptic plasticity during the course of experimental autoimmune encephalomyelitis.
Recent studies have shown that major histocompatibility complex class I (MHC I) expression directly influences the stability of nerve terminals. Also, the acute phase of experimental autoimmune encephalomyelitis (EAE) has shown a significant impact on inputs within the spinal cord. Therefore, the present work investigated the synaptic covering of motoneurons during the induction phase of disease and progressive remissions of EAE. EAE was induced in C57BL/6J mice, which were divided into four groups: normal, peak disease, first remission, and second remission. The animals were killed and their lumbar spinal cords processed for in situ hybridization (IH), immunohistochemistry, and transmission electron microscopy (TEM). The results indicated an increase in glial reaction during the peak disease. During this period, the TEM analysis showed a reduction in the synaptic covering of the motoneurons, corresponding to a reduction in synaptophysin immunolabeling and an increase in the MHC I expression. The IH analysis reinforced the immunolabeling results, revealing an increased expression of MHC I mRNA by motoneurons and nonneuronal cells during the peak disease and first remission. The results observed in both remission groups indicated a return of the terminals to make contact with the motoneuron surface. The ratio between excitatory and inhibitory inputs increased, indicating the potential for development of an excitotoxic process. In conclusion, the results presented here indicate that MHC I up-regulation during the course of EAE correlates with the periods of synaptic plasticity induced by the infiltration of autoreactive immune cells and that synaptic plasticity decreases after recurrent peaks of inflammation.
Freria
C M
CM
Laboratory of Nerve Regeneration, Department of Anatomy, Institute of Biology, University of Campinas-UNICAMP, CEP 13083-970, Campinas, SP, Brazil.
Zanon
R G
RG
Santos
L M B
LM
Oliveira
A L R
AL
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009046:Motor Neurons / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D009457:Neuroglia / Q000276:immunology* / Q000378:metabolism; D009473:Neuronal Plasticity; D017729:Presynaptic Terminals / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger; D012008:Recurrence; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D001613:beta 2-Microglobulin / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D016708:Synaptophysin; D001613:beta 2-Microglobulin