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

Abstract

Most of the motor disabilities occurring in multiple sclerosis and in its animal model - experimental autoimmune encephalomyelitis (EAE), have been classically attributed to the demyelinization process. However, the occurrence of major changes in the spinal cord network during the time course of the disease also trigger the clinical signs, as well as contributing to a rapid sensitive/motor recovery. The immunomodulador glatiramer acetate (GA) has been shown significantly reduce the seriousness of the symptoms during the course of the disease. However, its mechanism of action is not fully understood. Since GA may influence the response of non neuronal cells in the spinal cord, it is possible that, at certain extent, such drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after fifteen days of treatment and the spinal cords processed for immunohistochemical analysis (IH) and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labelling of synaptophysin and GFAP (Glial fibrillary acidic protein) using IH. Also an ultrastructural analysis of the terminals apposed to alpha motoneurons was performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labelling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, the ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals in comparison with the placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis. (AU)

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