Influence of Glatiramer acetate on the synaptic stability and glial reaction during the EAE and after motor root avulsion / Influencia do acetato de glatiramer (AG) sobre a estabilidade sinaptica e reação glial durante o curso da EAE e apos avulsão de raizes motoras

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Multiple sclerosis (MS) is an inflammatory and demyelinating disease, which etiology is unknown. Although it is the result of a major autoimmune response. The Glatiramer acetate (GA) is a drug used to treat MS and is composed by four peptides homologous to the myelin basic protein (MBP), that is able to reduce the exacerbation and injuries to the CNS. Nevertheless it is possible that GA develops a direct effect on the CNS by modulating the expression of the major histocompatibility complex of class I (MHC I), which has recently been involved in the synaptic plasticity process. For this study an animal model for MS was used, namely the experimental autoimmune encephalomyelitis (EAE) as well as the spinal motor root avulsion (AV) was used to investigate the synaptic plasticity and glial react in the CNS after GA treatment. EAE was induced in C57BL/6 mice which were divided into 4 groups. Thirty animals were induced to EAE and treated with GA, 15 animals were treated until the placebo group reached the exacerbation of the disease and other 15 animals were treated until the remission phase. The placebo treated group, treated up to the followed same procedures of the GA treated groups. However the animals were given only saline solution. In this way, 15 animals were treated up to the exacerbation phase and 15 animals were treated until the remission phase. The AV it was performed in 20 Lewis adult rats that were divided into 2 groups with 10 animals each. The first group was treated with GA (n=10) and second group was treated with saline (n=10) for 14 days. The treatment was initiated soon after the lesion. The EAE results were analyzed by immunohistochemistry (n = 5), Western Blotting (n = 5) and a qualitative analysis of spinal motoneurons and their afferents was also performed by transmission electron microscopy (n = 5). Avulsed animals (n=20) were divided into groups for the immunohistochemichal study (n=10) and for neuronal survival counting (n=10). The results showed that GA has the ability to decrease MHC class I expression in mice with EAE and in rats after AV. In this way, influences the synaptic plasticity and inflammatory processes regulation during the disease and after a mechanical injury. There was a decrease in astrocyte reactivity (GFAP-glial fibrillary acidic protein expression) and a decrease in microglial reactivity observed by Iba-1. Expression analyses immunolabeling was more preserved after GA administration and the neuronal count performed in the AV rats also showed increased motoneurons survival. Taken together, the present results indicate that GA plays a role in the CNS by reducing the MHC class I expression in the spinal cord and environmental. Thus providing better synaptic stability and neuronal preservation during the course of EAE and CNS lesion

ASSUNTO(S)

complexo principal de histocompatibilidade esclerose multipla encefalomielite auto-imune experimental multiple sclerosis encephalomyelitis major histocompatibility complex experimental autoimmune

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