Artículo
GABAergic agonists modulate the glutamate release from frontal cortex synaptosomes of rats with experimental autoimmune encephalomyelitis
Fecha de publicación:
10/2015
Editorial:
Bentham Science
Revista:
Inflamm Allergy Drug Targets.
ISSN:
1871-5281
e-ISSN:
2212-4055
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Resumen
Experimental autoimmune encephalomyelitis (EAE) is a model that mimics many of the clinical and pathological features of multiple sclerosis. We have previously found a significant reduction in the GABAergic regulation of glutamate release from synaptosomes of EAE rats during the acute stage of the disease. In order to deepen into the possible metabolic pathways responsible for this alteration, in this work we evaluate the direct effect of different GABAergic agonists on the glutamate release and synapsin I phosphorylation in synaptosomes from the frontal cortex of control and EAE animals. The results show that all tested GABA agonists negatively modulate control synaptosomes, downregulating glutamate release and synapsin I phosphorylation on P-site 3, while synaptosomes from EAE group are less responsive to GABAergic agonists, with no change in their sensitivity to allosteric modulators. GABA and the GABA receptor agonists Muscimol (GABAA agonist) and Baclofen (GABAB agonist) caused a decrease in glutamate release paralleled by a similar reduction in synapsin I phosphorylation. In the case of the benzodiazepines Diazepam and Clonazepam (GABAA allosteric agonists) there was a higher effect on synapsin I phosphorylation than in glutamate release. These results indicate that the extent of GABAergic modulation of presynaptic terminals depends on the type of agonist employed and this regulation is altered in the frontal cortex during the acute phase of EAE.
Palabras clave:
Multiple Sclerosis
,
Gaba
,
Synaptosomes
,
Benzodiazepines
Archivos asociados
Licencia
Identificadores
DOI:
http://dx.doi.org/
Colecciones
Articulos(CIQUIBIC)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Citación
Fernández Hurst, Nicolás; Chanaday Ricagni, Natalí Luján; Roth, German Alfredo; GABAergic agonists modulate the glutamate release from frontal cortex synaptosomes of rats with experimental autoimmune encephalomyelitis; Bentham Science; Inflamm Allergy Drug Targets.; 14; 2; 10-2015; 105-110
Compartir
Altmétricas