Marques K B, Santos L M B, Oliveira A L R
Departamento de Anatomia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, CEP 13083-970, Campinas, SP, Brazil.
Eur J Neurosci. 2006 Dec;24(11):3053-62. doi: 10.1111/j.1460-9568.2006.05184.x.
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.
在实验性自身免疫性脑脊髓炎病程中，运动和感觉功能出现大量丧失，这在传统上被归因于脱髓鞘过程。在大鼠中，临床症状在完全四肢瘫痪后5天内消失，这表明脱髓鞘可能不是该疾病快速进展的唯一原因。本研究调查了实验性自身免疫性脑脊髓炎在病情加重期和缓解期诱导的脊髓运动神经元突触覆盖变化的发生情况。通过透射电子显微镜将终末分为C型、F型和S型。还使用了突触素、胶质纤维酸性蛋白以及小胶质细胞/巨噬细胞标志物F4/80的免疫组织化学分析，以便在突触变化与胶质反应之间建立关联。超微结构分析表明，在病情加重期，F型和S型终末均有强烈回缩。从这个意义上说，剩余终末的覆盖范围和长度均大幅减少。然而，尽管平均长度仍较短，但回缩的终末迅速恢复并重新并列。缓解后F型终末数量多于对照组，可能发生了一定程度的芽生。免疫组织化学分析表明，突触丧失的峰值与大、小胶质细胞反应增强同时出现。我们的结果表明，在疾病病程中脊髓网络发生的主要变化可能对临床症状的产生有显著贡献，并有助于解释其快速恢复。
