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

Abstract

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model -experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this 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 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to 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.

Treatment of Chronic Experimental Autoimmune Encephalomyelitis with Epigallocatechin-3-Gallate and Glatiramer Acetate Alters Expression of Heme-Oxygenase-1

“…This corresponded with a decrease in leukocyte infiltration in the CNS of the GA-treated animals. Although we injected only one dose of 150 μg GA, these results are in agreement with the previously reported anti-inflammatory properties of GA in mouse and rat EAE [ 25 , 26 ]. It is also possible that EGCG might interfere with the actions of GA.…”

Regular Exercise Modifies Histopathological Outcomes of Pharmacological Treatment in Experimental Autoimmune Encephalomyelitis

“…Therefore, from the 21st dpi, mice were treated with glatiramer acetate (EAE-GA and EAE-Ex-GA groups); dimethyl fumarate (EAE-DMF and EAE-Ex-DMF groups) or were just followed as control groups (EAE and EAE-Ex groups). For GA treatment, animals received a subcutaneous injection at a dose of 0.5 mg/animal/day for 7 days ( 16 , 17 ) and DMF was administered by gavage (diluted in 0.08% methylcellulose solution) at a dose of 15 mg/kg for 14 days ( 18 ).…”

Impact of pregabalin treatment on synaptic plasticity and glial reactivity during the course of experimental autoimmune encephalomyelitis

“…We have previously shown that important synaptic changes take place in the spinal cord during the exacerbation of the disease, what may involve glutamatergic excitotoxicity (Marques et al. ; Scorisa et al. ).…”