RESUMO
Leptin is a permissive factor for puberty initiation, participating as a metabolic cue in the activation of the kisspeptin (Kiss1)-gonadotropin-releasing hormone neuronal circuitry; however, it has no direct effect on Kiss1 neurons. Leptin acts on hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons, participating in the regulation of energy homeostasis. We investigated the influence of a short-term high-fat diet (HFD) on the effect of leptin on puberty timing. Kiss1-hrGFP female mice received a HFD or regular diet (RD) after weaning at postnatal day (PN)21 and were studied at PN28 and PN32. The HFD increased body weight and plasma leptin concentrations and decreased the age at vaginal opening (HFD, 32 ± 0.53 days; RD, 38 ± 0.67 days). Similar colocalization of neurokinin B and dynorphin in Kiss1-hrGFP neurons of the arcuate nucleus (ARC) was observed between the HFD and RD groups. The HFD increased CART expression in the ARC and Kiss1 messenger RNA expression in the anteroventral periventricular (AVPV)/anterior periventricular (Pe). The HFD also increased the number of ARC CART neurons expressing leptin-induced phosphorylated STAT3 (signal transducer and activator of transcription 3) at PN32. Close apposition of CART fibers to Kiss1-hrGFP neurons was observed in the ARC of both RD- and HFD-fed mice. In conclusion, these data reinforce the notion that a HFD increases kisspeptin expression in the AVPV/Pe and advances puberty initiation. Furthermore, we have demonstrated that the HFD-induced earlier puberty is associated with an increase in CART expression in the ARC. Therefore, these data indicate that CART neurons in the ARC can mediate the effect of leptin on Kiss1 neurons in early puberty induced by a HFD.
Assuntos
Dieta Hiperlipídica , Gorduras na Dieta/farmacologia , Leptina/metabolismo , Leptina/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Animais , Feminino , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo , Fatores de TempoRESUMO
Modulation of salt appetite involves interactions between the circumventricular organs (CVOs) receptive areas and inhibitory hindbrain serotonergic circuits. Recent studies provide support to the idea that the serotonin action in the lateral parabrachial nucleus (LPBN) plays an important inhibitory role in the modulation of sodium appetite. The aim of the present work was to identify the specific groups of neurons projecting to the LPBN that are activated in the course of sodium appetite regulation, and to analyze the associated endocrine response, specifically oxytocin (OT) and atrial natriuretic peptide (ANP) plasma release, since both hormones have been implicated in the regulatory response to fluid reestablishment. For this purpose we combined the detection of a retrograde transported dye, Fluorogold (FG) injected into the LPBN with the analysis of the Fos immunocytochemistry brain pattern after sodium intake induced by sodium depletion. We analyzed the Fos-FG immunoreactivity after sodium ingestion induced by peritoneal dialysis (PD). We also determined OT and ANP plasma concentration by radioimmunoassay (RIE) before and after sodium intake stimulated by PD. The present study identifies specific groups of neurons along the paraventricular nucleus, central extended amygdala, insular cortex, dorsal raphe nucleus, nucleus of the solitary tract and the CVOs that are activated during the modulation of sodium appetite and have direct connections with the LPBN. It also shows that OT and ANP are released during the course of sodium satiety and fluid reestablishment. The result of this brain network activity may enable appropriate responses that re-establish the body fluid balance after induced sodium consumption.
Assuntos
Regulação do Apetite/fisiologia , Fator Natriurético Atrial/sangue , Sistema Endócrino/fisiologia , Ocitocina/sangue , Núcleos da Rafe/metabolismo , Sódio na Dieta , Vias Aferentes/efeitos dos fármacos , Análise de Variância , Animais , Regulação do Apetite/efeitos dos fármacos , Estimulação Elétrica/métodos , Masculino , Proteínas Oncogênicas v-fos/metabolismo , Diálise Peritoneal , Radioimunoensaio/métodos , Núcleos da Rafe/citologia , Ratos , Ratos Wistar , Sódio/farmacologia , Estilbamidinas/metabolismoRESUMO
Recent evidence has shown that the serotonergic mechanism of the lateral parabrachial nucleus (LPBN) participates in the regulation of renal and hormonal responses to isotonic blood volume expansion (BVE). We investigated the BVE-induced Fos activation along forebrain and hindbrain nuclei and particularly within the serotonergic clusters of the raphé system that directly project to the LPBN. We also examined whether there are changes in the concentration of serotonin (5HT) within the raphé nucleus in response to the same stimulus. With this purpose, we analyzed the cells doubly labeled for Fos and Fluorogold (FG) following BVE (NaCl 0.15 M, 2 ml/100 g b.w., 1 min) 7 days after FG injection into the LPBN. Compared with the control group, blood volume-expanded rats showed a significant greater number of Fos-FG double-labeled cells along the nucleus of the solitary tract, locus coeruleus, hypothalamic paraventricular nucleus, central extended amygdala complex, and dorsal raphé nucleus (DRN) cells. Our study also showed an increase in the number of serotonergic DRN neurons activated in response to isotonic BVE. We also observed decreased levels of 5HT and its metabolite 5-hydroxyindoleacetic acid (measured by high-pressure liquid chromatography) within the raphé nucleus 15 min after BVE. Given our previous evidence on the role of the serotonergic system in the LPBN after BVE, the present morphofunctional findings suggest the existence of a key pathway (DRN-LPBN) that may control BVE response through the modulation of 5HT release.
Assuntos
Vias Autônomas/metabolismo , Volume Sanguíneo/fisiologia , Ponte/metabolismo , Núcleos da Rafe/metabolismo , Serotonina/metabolismo , Fibras Aferentes Viscerais/metabolismo , Animais , Vias Autônomas/citologia , Biomarcadores/análise , Biomarcadores/metabolismo , Pressão Sanguínea/fisiologia , Volume Sanguíneo/efeitos dos fármacos , Mapeamento Encefálico , Ácido Hidroxi-Indolacético/metabolismo , Hipertensão/fisiopatologia , Masculino , Ponte/citologia , Terminações Pré-Sinápticas/metabolismo , Proteínas Proto-Oncogênicas c-fos/análise , Proteínas Proto-Oncogênicas c-fos/metabolismo , Núcleos da Rafe/citologia , Ratos , Ratos Wistar , Cloreto de Sódio/farmacologia , Coloração e Rotulagem , Estilbamidinas , Transmissão Sináptica/fisiologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , Fibras Aferentes Viscerais/citologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
The presence of nitric oxide synthase (NOS), the enzyme that catalyses the formation of nitric oxide (NO), in the circumventricular organs and magnocellular neurones suggests an important role of NO in the modulation of vasopressin (AVP) and oxytocin (OT) release. Intracerebroventricular (I.C.V.) injection of angiotensin II (Ang II) stimulates the release of AVP, OT and atrial natriuretic peptide (ANP), with the resultant antidiuretic and natriuretic effects. This study investigated the interaction between nitrergic and angiotensinergic pathways on the release of AVP, OT and ANP and on urinary volume and sodium excretion in water-loaded rats. Unanaesthetized, freely moving, male Wistar rats received two water loads followed by an injection into the lateral ventricle of an inhibitor of NOS (L-NAME), a NO donor [3-morpholinylsydnoneimine chloride (SIN-1) or S-nitroso-N-acetyl penicillamine (SNAP)] or vehicle (isotonic saline) and, 20 min after, they received a second I.C.V. injection of Ang II or vehicle. Injections of L-NAME or Ang II produced an increase in plasma levels of AVP, OT and ANP, a reduction in urinary volume and an increase in sodium excretion. Pretreatment with L-NAME enhanced the Ang II-induced increase in AVP, OT and ANP release, as well as the antidiuresis and natriuresis. Injection of SIN-1 or SNAP did not modify hormonal plasma levels and urinary parameters. In contrast SNAP blocked the AVP, OT and ANP release, as well as antidiuretic and natriuretic responses induced by ANG-II. Thus, the central nitrergic system can act to inhibit AVP, OT and ANP secretion and the antidiuretic and natriuretic effects in response to Ang II.
Assuntos
Angiotensina II/farmacologia , Natriurese/efeitos dos fármacos , Natriurese/fisiologia , Óxido Nítrico/metabolismo , Hormônios Peptídicos/sangue , Vasoconstritores/farmacologia , Animais , Fator Natriurético Atrial/sangue , Estado de Consciência , Inibidores Enzimáticos/farmacologia , Injeções Intraventriculares , Masculino , Molsidomina/análogos & derivados , Molsidomina/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Concentração Osmolar , Ocitocina/sangue , Ratos , Ratos Wistar , S-Nitroso-N-Acetilpenicilamina/farmacologia , Sódio/urina , Urina , Vasopressinas/sangueRESUMO
This study investigated the involvement of serotonergic mechanisms of the lateral parabrachial nucleus (LPBN) in the control of sodium (Na+) excretion, potassium (K+) excretion, and urinary volume in unanesthetized rats subjected to acute isotonic blood volume expansion (0.15 M NaCl, 2 ml/100 g of body wt over 1 min) or control rats. Plasma oxytocin (OT), vasopressin (VP), and atrial natriuretic peptide (ANP) levels were also determined in the same protocol. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. In rats treated with vehicle in the LPBN, blood volume expansion increased urinary volume, Na+ and K+ excretion, and also plasma ANP and OT. Bilateral injections of serotonergic receptor antagonist methysergide (1 or 4 microg/200 etal) into the LPBN reduced the effects of blood volume expansion on increased Na+ and K+ excretion and urinary volume, while LPBN injections of serotonergic 5-HT(2a)/HT(2c) receptor agonist, 2.5-dimetoxi-4-iodoamphetamine hydrobromide (DOI; 1 or 5 microg/200 etal) enhanced the effects of blood volume expansion on Na+ and K+ excretion and urinary volume. Methysergide (4 microg) into the LPBN decreased the effects of blood volume expansion on plasma ANP and OT, while DOI (5 microg) increased them. The present results suggest the involvement of LPBN serotonergic mechanisms in the regulation of urinary sodium, potassium and water excretion, and hormonal responses to acute isotonic blood volume expansion.