Spinal motoneuron synaptic plasticity during the course of an animal model of multiple sclerosis.
During the course of experimental autoimmune encephalomyelitis, a massive loss of motor and sensitive function occurs, which has been classically attributed to the demyelination process. In rats, the clinical signs disappear within 5 days following complete tetraplegia, indicating that demyelination might not be the only cause for the rapid evolution of the disease. The present work investigated the occurrence of experimental autoimmune encephalomyelitis-induced changes of the synaptic covering of spinal motoneurons during exacerbation and after remission. The terminals were typed with transmission electron microscopy as C-, F- and S-type. Immunohistochemical analysis of synaptophysin, glial fibrillary acidic protein and the microglia/macrophage marker F4/80 were also used in order to draw a correlation between the synaptic changes and the glial reaction. The ultrastructural analysis showed that, during exacerbation, there was a strong retraction of both F- and S-type terminals. In this sense, both the covering as well as the length of the remaining terminals suffered great reductions. However, the retracted terminals rapidly returned to apposition, although the mean length remained shorter. A certain level of sprouting may have occurred as, after remission, the number of F-terminals was greater than in the control group. The immunohistochemical analysis showed that the peak of synaptic loss was coincident with an increased macro- and microglial reaction. Our results suggest that the major changes occurring in the spinal cord network during the time course of the disease may contribute significantly to the origin of the clinical signs as well as help to explain their rapid recovery.
Marques
K B
KB
Departamento de Anatomia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, CEP 13083-970, Campinas, SP, Brazil.
Santos
L M B
LM
Oliveira
A L R
AL
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016253:Microscopy, Immunoelectron; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D009416:Nerve Regeneration / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016708:Synaptophysin / Q000378:metabolism
D000943:Antigens, Differentiation; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D016708:Synaptophysin; C036763:monocyte-macrophage differentiation antigen