RESUMO
Background and Objectives: The commissural nucleus of the tractus solitarius (cNTS) not only responds to glucose levels directly, but also receives afferent signals from the liver, and from the carotid chemoreceptors (CChR). In addition, leptin, through its receptors in the cNTS, regulates food intake, body weight, blood glucose levels, and brain glucose retention (BGR). These leptin effects on cNTS are thought to be mediated through the sympathetic-adrenal system. How these different sources of information converging in the NTS regulate blood glucose levels and brain glucose retention remains largely unknown. The goal of the present study was to determine whether the local administration of leptin in cNTS alone, or after local anoxic stimulation using sodium cyanide (NaCN) in the carotid sinus, modifies the expression of leptin Ob-Rb and of c-Fos mRNA. We also investigated how leptin, alone, or in combination with carotid sinus stimulation, affected brain glucose retention. Materials and Methods: The experiments were carried out in anesthetized male Wistar rats artificially ventilated to maintain homeostatic values for pO2, pCO2, and pH. We had four groups: (a) experimental 1, leptin infusion in cNTS and NaCN in the isolated carotid sinus (ICS; n = 10); (b) experimental 2, leptin infusion in cNTS and saline in the ICS (n = 10); (c) control 1, artificial cerebrospinal fluid (aCSF) in cNTS and NaCN in the ICS (n = 10); (d) control 2, aCSF in cNTS and saline in the ICS (n = 10). Results: Leptin in cNTS, preceded by NaCN in the ICS increased BGR and leptin Ob-Rb mRNA receptor expression, with no significant increases in c-Fos mRNA in the NTSc. Conclusions: Leptin in the cNTS enhances brain glucose retention induced by an anoxic stimulus in the carotid chemoreceptors, through an increase in Ob-Rb receptors, without persistent changes in neuronal activation.
Assuntos
Corpo Carotídeo , Leptina , Receptores para Leptina , Núcleo Solitário , Animais , Glicemia/metabolismo , Corpo Carotídeo/metabolismo , Glucose/metabolismo , Hipóxia , Leptina/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores para Leptina/metabolismo , Núcleo Solitário/metabolismoRESUMO
The application of sodium cyanide (NaCN) to the carotid body receptors (CBR) (CBR stimulation) induces rapid blood hyperglycemia and an increase in brain glucose retention. The commissural nucleus tractus solitarius (cNTS) is an essential relay nucleus in this hyperglycemic reflex; it receives glutamatergic afferents (that also release brain derived neurotrophic factor, BDNF) from the nodose-petrosal ganglia that relays CBR information. Previous work showed that AMPA in NTS blocks hyperglycemia and brain glucose retention after CBR stimulation. In contrast, BDNF, which attenuates glutamatergic AMPA currents in NTS, enhances these glycemic responses. Here we investigated the combined effects of BDNF and AMPA (and their antagonists) in NTS on the glycemic responses to CBR stimulation. Microinjections of BDNF plus AMPA into the cNTS before CBR stimulation in anesthetized rats, induced blood hyperglycemia and an increase in brain arteriovenous (a-v) of blood glucose concentration difference, which we infer is due to increased brain glucose retention. By contrast, the microinjection of the TrkB antagonist K252a plus AMPA abolished the glycemic responses to CBR stimulation similar to what is observed after AMPA pretreatments. In BDNF plus AMPA microinjections preceding CBR stimulation, the number of c-fos immunoreactive cNTS neurons increased. In contrast, in the rats microinjected with K252a plus AMPA in NTS, before CBR stimulation, c-fos expression in cNTS decreased. The expression of AMPA receptors GluR2/3 did not change in any of the studied groups. These results indicate that BDNF in cNTS plays a key role in the modulation of the hyperglycemic reflex initiated by CBR stimulation.