ABSTRACT
Estudios previos de nuestro laboratorio han mostrado que diez minutos después de la administración sistémica de corticosterona se dificulta la recuperación de la memoria espacial en el laberinto de Barnes, sin embargo se desconocen los mecanismos que subyacen a este efecto. Dado que los glucocorticoides ejercen sus acciones a través de los receptores de tipo GR y MR, en el presente estudio se evaluó la participación de estos receptores en el efecto perjudicial rápido de la corticosterona sobre la memoria espacial. Para ello 37 ratas Wistar macho fueron entrenadas en la tarea y 24h después recibieron una inyección subcutánea de antagonista GR, antagonista MR o vehículo. 50min después los animales fueron inyectados con corticosterona o vehículo por vía intraperitoneal y 10min después se evaluó la recuperación de la memoria espacial. Los resultados mostraron que la corticosterona perjudicó rápidamente la recuperación de la memoria espacial a largo plazo, pues los animales inyectados con esta hormona presentaron mayores latencias de escape, mayor número de errores, mayor número de exploraciones y mayor distancia recorrida hasta alcanzar la meta; un efecto revertido solamente con la administración del antagonista MR. Este hallazgo concuerda con estudios in vitro donde se muestra que los efectos rápidos de la corticosterona sobre la trasmisión glutamatérgica en el hipocampo están mediados por los receptores MR.
Previous studies of our laboratory have shown that it is difficult to recover the spatial memory in the Barnes maze ten minutes after a systemic administration of corticosterone; however the mechanisms that underlie this effect are unknown. Considering glucocorticoids exert their actions through GR and MR type receptors, the present study evaluated the participation of these receptors in the rapid damaging effect of corticosterone on spatial memory. For this, 37 male Wistar rats were trained on the task and 24 h afterwards they received a subcutaneous injection of GR antagonist, MR antagonist or vehicle. 50 min later the animals were injected with corticosterone or vehicle intraperitoneally and 10 min later, the spatial memory recovery was evaluated. The results indicated that corticosterone rapidly impaired spatial long-term memory recovery, as animals injected with this hormone presented higher escape latencies, more errors, higher exploration and greater traveled distance to reach the goal; an effect reverted only with the administration of the MR antagonist. This finding agrees with in vitro studies showing that the rapid effects of corticosterone on glutamatergic transmission in the hippocampus are mediated by MR receptors.
ABSTRACT
OBJECTIVES: To analyze glucocorticoid (GC) sensitivity using intravenous very low dose dexamethasone suppression test (IV-VLD-DST) in patients with rheumatoid arthritis (RA) and its correlation with glucocorticoid receptor alpha-isoform (GRα) gene expression. METHODS: We evaluated 20 healthy controls and 32 RA patients with Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 joints (DAS) scores and IV-VLD-DST and GRα expression in mononuclear cells. RESULTS: Basal cortisol and the percentage of cortisol reduction after IV-VLD-DST were lower in RA patients than in controls, whereas GRα expression was similar among groups. In the RA group there was an inverse correlation between GRα expression and the percentage of cortisol suppression that was not observed in controls. There was a direct relationship between DAS and GRα expression. CONCLUSIONS: Mechanisms involved in GC resistance observed in patients with RA are possibly not at the level of GRα gene expression, since it was similar among groups and GRα increased with disease activity.
OBJETIVOS: Determinar a sensibilidade aos glicocorticóides (GC) utilizando teste de supressão com dexametasona em doses muito baixas (IV-VLD-DST) em pacientes com artrite reumatóide (AR) e sua correlação com a expressão gênica da isoforma alfa do receptor glicocorticóide (GRα). MÉTODOS: Foram avaliados 20 controles saudáveis e 32 pacientes com AR com Health Assessment Questionnaire (HAQ) e Disease Activity Score 28 joints (DAS), IV-VLD-DST e expressão do GRα em células mononucleares. RESULTADOS: Cortisol basal e porcentagem de redução do cortisol após IV-VLD-DST foram menores no grupo AR do que nos controles, enquanto a expressão de GRα foi similar entre eles. No grupo com AR, ocorreu correlação negativa entre a expressão do GRα e a porcentagem de supressão do cortisol, enquanto nos controles não houve correlação. Ocorreu relação direta entre DAS e expressão de GRα . CONCLUSÕES: Sugerimos que os mecanismos envolvidos na resistência aos GC observada na AR não estejam ao nível da expressão gênica do GRα, já que esta é igual entre os grupos e aumenta com a gravidade da doença.