Spinal motoneuron synaptic plasticity during the course of an animal model of multiple sclerosis

Abstract

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.

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model

“…Thereafter, the lumbar intumescence was dissected out, postfixed overnight and then frozen. For electron microscopy, 100 mL of a fixative containing 2.5% glutaraldehyde and 0.5% paraformaldehyde in sodium phosphate buffer, pH 7.4, were perfused through the ascending aorta as previously described (5). The lumbar Glatiramer acetate increases spinal cord synaptic stability www.bjournal.com.br spinal cord was removed and stored overnight in the same fixative at 4°C.…”

“…Demyelination similar to that seen during the course of MS may be induced in animals, in a model called experimental autoimmune encephalomyelitis (EAE) (1)(2)(3)(4)(5). During the course of EAE, damage to the axons as well as the occurrence of synaptic plasticity phenomena in the brain and spinal cord contribute to the clinical signs of the disease (3,6,7).…”

“…During the course of EAE, damage to the axons as well as the occurrence of synaptic plasticity phenomena in the brain and spinal cord contribute to the clinical signs of the disease (3,6,7). Synaptic plasticity in the spinal cord may explain, at least in part, the rapid sensorimotor recovery of the animals soon after tetraplegia (3,5). In view of the importance of a better understanding of MS as well as its experimental models, major advances in understanding how cellular and humoral immune responses contribute to the pathogenesis of these diseases have been made in recent years (8)(9)(10)(11)(12).…”

The Beneficial Effects of Treadmill Step Training on Activity-Dependent Synaptic and Cellular Plasticity Markers After Complete Spinal Cord Injury

“…These studies support the important role of this protein in synaptic function and plasticity. In this context, qualitative and quantitative analyses of the immunoreactivity of the synaptic protein synaptophysin have been performed in the spinal cord motor nuclei of rats in order to assess the changes in synaptic activity during the course of nervous system pathology [53] and activity dependent plasticity [46]. The up-regulation of the synaptic proteins may be a result of the lumbar circuitry synaptic plasticity and the regeneration of supraspinal descending axons upon lower neural structures in incomplete SCI [54].…”

Nitric Oxide and TNFα Effects in Experimental Autoimmune Encephalomyelitis Demyelination

“…TGF ␤ , IL-4 and IL-10, previously reported in the recovery phase of EAE; since such cytokines are known to inhibit activation of the macrophages/microglia and the production of NO [27,28] , this leads to a consequent reduction in the severity of EAE. Moreover, recent studies have demonstrated that in EAE, neurodegeneration is responsible for the chronic neurological deficit following the inflammatory response [29,30] . In the acute phase of EAE, macrophages play an important role in the pathogenesis of axonal injury and axon loss, demyelination and inflammation, all significantly correlated with clinical severity scores.…”