RESUMO
Sodium (Na) homeostasis is crucial for life, and Na levels in body fluids are constantly monitored in the brain. The subfornical organ (SFO) is the center of the sensing responsible for the control of salt-intake behavior, where Na(x) channels are expressed in specific glial cells as the Na-level sensor. Here, we show direct interaction between Na(x) channels and alpha subunits of Na(+)/K(+)-ATPase, which brings about Na-dependent activation of the metabolic state of the glial cells. The metabolic enhancement leading to extensive lactate production was observed in the SFO of wild-type mice, but not of the Na(x)-knockout mice. Furthermore, lactate, as well as Na, stimulated the activity of GABAergic neurons in the SFO. These results suggest that the information on a physiological increase of the Na level in body fluids sensed by Na(x) in glial cells is transmitted to neurons by lactate as a mediator to regulate neural activities of the SFO.
Assuntos
Encéfalo/metabolismo , Lactatos/metabolismo , Neuroglia/metabolismo , Neurônios/fisiologia , Transdução de Sinais/fisiologia , Canais de Sódio/fisiologia , Sódio/metabolismo , Animais , Encéfalo/citologia , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Glioma , Glucose/metabolismo , Glutamato Descarboxilase/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Isoenzimas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neuroglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Ouabaína/farmacologia , Ratos , Órgãos dos Sentidos/citologia , Órgãos dos Sentidos/fisiologia , Sódio/farmacologia , Canais de Sódio/deficiência , ATPase Trocadora de Sódio-Potássio/fisiologia , TransfecçãoRESUMO
In dehydrated animals, the antidiuretic hormone vasopressin (VP) is released from the nerve terminals of magnocellular neurons of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) into the systemic circulation at the posterior pituitary. Increases in sodium (Na+)-level and osmolality in body fluids upon dehydration are reportedly sensed by a Na+-sensor and/or an osmosensor, respectively. However, it is still unknown whether both are involved in the regulation of production and/or release of VP. Na(x) is the cerebral Na+-level sensor and Na(x)-knockout mice do not stop ingesting salt even when dehydrated. Here we examined VP production/release in Na(x)-knockout mice, and found that they are normal in the VP response to dehydration or intraperitoneal-administration with hypertonic saline. In situ hybridization using an intron-specific probe showed that VP gene expression in the SON did not differ from wild-type mice when dehydrated. Also, there was no significant difference in the activity of subfornical organ neurons projecting to the SON between the two genotypes when stimulated by water deprivation. Furthermore, Na(x)-knockout mice showed a normal response in urine excretion to dehydration. All these results indicate that the information of Na+-level increase detected by Na(x) does not contribute to the control of VP production/release.