RESUMEN
Glial cell-derived nitric oxide (NO.) and its regulation has significant implications for central nervous system pathophysiology. The aim of the present study was to determine the production of NO. by cultured rat astrocytes and peritoneal macrophages, and its regulation by glucocorticoids. Results corroborate the presence of both constitutive and induced NO. synthase (cNOS and iNOS) in astrocytes, while macrophages express only the inducible isoform. Dexamethasone was able to decrease NO. synthesis produced by induction of iNOS in macrophage and astrocyte phagocytosis, but not the NO. produced by the cNOS spontaneously expressed in cultured astrocytes.
Asunto(s)
Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Dexametasona/farmacología , Glucocorticoides/farmacología , Óxido Nítrico/biosíntesis , Animales , Animales Recién Nacidos , Astrocitos/citología , Células Cultivadas , Corteza Cerebral/citología , Ratas , Ratas Sprague-DawleyRESUMEN
The Wobbler mouse, a model of amyotrophic lateral sclerosis (ALS), presents motorneuron degeneration and pronounced astrogliosis in the spinal cord. We have studied factors controlling astrocyte proliferation in cultures derived from Wobbler and control mice spinal cord. Basal rate of [3H]thymidine incorporation was 15 times lower in Wobbler astrocytes. While in control cultured cells interleukin-1alpha (IL-1) and corticosterone (CORT) significantly increased proliferation, both agents were inactive in Wobbler astrocytes. The lack of response to CORT was not due to the absence of glucocorticoid receptors, because similar receptor amounts were found in Wobbler and control astrocytes. In contrast to IL-1 and CORT, transforming growth factor-beta1 (TGF-beta1) substantially increased proliferation of Wobbler astrocytes but not of control cells. Differences in response to TGF-beta1 were also obtained by measuring glial fibrillary acidic protein (GFAP) immunoreaction intensity, which was substantially higher in Wobbler astrocytes. Thus, abnormal responses to different mitogens characterized Wobbler astrocytes in culture. We suggest that TGF-beta1 may play a role in the reactive gliosis and GFAP hyperexpression found in the degenerating spinal cord of this model of ALS.
Asunto(s)
Astrocitos/metabolismo , Receptores de Glucocorticoides/metabolismo , Médula Espinal/metabolismo , Animales , Astrocitos/citología , Astrocitos/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , Corticosterona/farmacología , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/genética , Gliosis/patología , Interleucina-1/farmacología , Cinética , Masculino , Ratones , Ratones Endogámicos , Ratones Mutantes Neurológicos , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/patología , Fármacos Neuroprotectores/farmacología , Pregnatrienos/farmacología , Valores de Referencia , Médula Espinal/citología , Médula Espinal/efectos de los fármacos , Timidina/metabolismo , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
Glial cell-derived nitric oxide (NO.) and its regulation has significant implications for central nervous system pathophysiology. The aim of the present study was to determine the production of NO. by cultured rat astrocytes and peritoneal macrophages, and its regulation by glucocorticoids. Results corroborate the presence of both constitutive and induced NO. synthase (cNOS and iNOS) in astrocytes, while macrophages express only the inducible isoform. Dexamethasone was able to decrease NO. synthesis produced by induction of iNOS in macrophage and astrocyte phagocytosis, but not the NO. produced by the cNOS spontaneously expressed in cultured astrocytes