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MHC 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 of 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 4 groups: normal, peak disease, first remission and second remission. The animals were sacrificed and their lumbar spinal cords were 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 non-neuronal cells during the peak disease and 1st 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/inhibitory inputs increased, indicating the potential for development of an excitotoxic process. In conclusion, the results presented herein indicated that MHC I upregulation during the course of EAE correlates with the periods of synaptic plasticity induced by the infiltration of auto-reactive immune cells, and that synaptic plasticity decreases after recurrent peaks of inflammation. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FRERIA, C. M.; ZANON, R. G.; SANTOS, L. M. B.; OLIVEIRA, A. L. R.. Major Histocompatability Complex Class I Expression and Glial Reaction Influence Spinal Motoneuron Synaptic Plasticity During the Course of Experimental Autoimmune Encephalomyelitis. JOURNAL OF COMPARATIVE NEUROLOGY, v. 518, n. 7, p. 990-1007, . (09/16879-6)

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