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1.
Horm Behav ; 114: 104551, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31279703

RESUMO

The neuropeptides oxytocin and vasopressin and their receptors have established roles in the regulation of mammalian social behavior including parental care, sex, affiliation and pair-bonding, but less is known regarding their relationship to social dominance and subordination within social hierarchies. We have previously demonstrated that male mice can form stable linear dominance hierarchies with individuals occupying one of three classes of social status: alpha, subdominant, subordinate. Alpha males exhibit high levels of aggression and rarely receive aggression. Subdominant males exhibit aggression towards subordinate males but also receive aggression from more dominant individuals. Subordinate males rarely exhibit aggression and receive aggression from more dominant males. Here, we examined whether variation in social status was associated with levels of oxytocin (OTR) and vasopressin 1a (V1aR) receptor binding in socially relevant brain regions. We found that socially dominant males had significantly higher OTR binding in the nucleus accumbens core than subordinate animals. Alpha males also had higher OTR binding in the anterior olfactory nucleus, posterior part of the cortical amygdala and rostral lateral septum compared to more subordinate individuals. Conversely, alpha males had lower V1aR binding in the rostral lateral septum and lateral preoptic area compared to subordinates. These observed relationships have two potential explanations. Preexisting individual differences in the patterns of OTR and V1aR binding may underlie behavioral differences that promote or inhibit the acquisition of social status. More likely, the differential social environments experienced by dominant and subordinate animals may shift receptor expression, potentially facilitating the expression of adaptive social behaviors.


Assuntos
Encéfalo/metabolismo , Hierarquia Social , Ocitocina/metabolismo , Receptores de Vasopressinas/metabolismo , Agressão/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Núcleo Accumbens/metabolismo , Ligação do Par , Receptores de Ocitocina/metabolismo , Comportamento Social , Predomínio Social , Meio Social , Vasopressinas/metabolismo
2.
PLoS One ; 14(7): e0219205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269062

RESUMO

In the rat, oxytocin (OT) produces dose-dependent diuretic and natriuretic responses. Post-translational enzymatic conversion of the OT biosynthetic precursor forms both mature and C-terminally extended peptides. The plasma concentrations of these C-terminally extended peptides (OT-G; OT-GK and OT-GKR) are elevated in newborns and pregnant rats. Intravenous injection of OT-GKR to rats inhibits diuresis, whereas injection of amidated OT stimulates diuresis. Since OT and OT-GKR show different effects on the urine flow, we investigated whether OT-GKR modulates renal action by inhibition of the arginine-vasopressin (AVP) receptor V2 (V2R), the receptor involved in renal water reabsorption. Experiments were carried out in the 8-week-old Wistar rats receiving intravenous (iv) injections of vehicle, OT, OT-GKR or OT+OT-GKR combination. OT (10 µmol/kg) increased urine outflow by 40% (P<0.01) and sodium excretion by 47% (P<0.01). Treatment with OT-GKR (10 µmol/kg) decreased diuresis by 50% (P<0.001), decreased sodium excretion by 50% (P<0.05) and lowered potassium by 42% (P<0.05). OT antagonist (OTA) reduced diuresis and natriuresis exerted by OT, whereas the anti-diuretic effect of OT-GKR was unaffected by OTA. The treatment with V2R antagonist (V2A) in the presence and absence of OT induced diuresis, sodium and potassium outflow. V2A in the presence of OT-GKR only partially increased diuresis and natriuresis. Autoradiography and molecular docking analysis showed potent binding of OT-GKR to V2R. Finally, the release of cAMP from CHO cells overexpressing V2 receptor was induced by low concentration of AVP (EC50:4.2e-011), at higher concentrations of OT (EC50:3.2e-010) and by the highest concentrations of OT-GKR (EC50:1.1e-006). OT-GKR potentiated cAMP release when combined with AVP, but blocked cAMP release when combined with OT. These results suggest that OT-GKR by competing for the OT renal receptor (OTR) and binding to V2R in the kidney, induces anti-diuretic, anti-natriuretic, and anti-kaliuretic effects.


Assuntos
Diurese , Natriurese , Ocitocina/metabolismo , Animais , Autorradiografia , Ligação Competitiva , Células CHO , Linhagem Celular , Cricetinae , Cricetulus , AMP Cíclico/metabolismo , Eletrólitos/metabolismo , Humanos , Rim/metabolismo , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Ratos , Ratos Wistar , Receptores de Vasopressinas/metabolismo , Micção , Vasopressinas/metabolismo
3.
Pan Afr Med J ; 32: 210, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31312322

RESUMO

Disorders of water balance are a disease commonly encountered in our clinical practice. Analysis of vasopressin receptor type II (V2R) is essential to understand the physiology of water balance and it is used as a biological prototype of G protein-coupled receptors (GPCRs). Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a syndrome of inappropriate antidiuretic hormone secretion (SIADH) with low plasmatic vasopressin. The evidence on the role of V2 receptor and of aquaporin (AQP) in the mechanism of action for antidiuretic hormone (ADH) was based on the identification of protein gene mutations in patients with nephrogenic diabetes insipidus and NSIAD syndrome. V2R activating mutations were found in patients with NSIAD, contrasting with the numerous V2R inactivating mutations related to X-linked mutations described in patients with nephrogenic diabetes insipidus.


Assuntos
Diabetes Insípido Nefrogênico/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Síndrome de Secreção Inadequada de HAD/fisiopatologia , Receptores de Vasopressinas/genética , Aquaporinas/metabolismo , Diabetes Insípido Nefrogênico/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Síndrome de Secreção Inadequada de HAD/genética , Mutação , Neurofisinas/metabolismo , Precursores de Proteínas/metabolismo , Receptores de Vasopressinas/metabolismo , Vasopressinas/sangue , Vasopressinas/metabolismo
4.
Curr Obes Rep ; 8(3): 301-316, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31240613

RESUMO

PURPOSE OF REVIEW: The neurohypophysial endocrine system is identified here as a potential target for therapeutic interventions toward improving obesity-related metabolic dysfunction, given its coinciding pleiotropic effects on psychological, neurological and metabolic systems that are disrupted in obesity. RECENT FINDINGS: Copeptin, the C-terminal portion of the precursor of arginine-vasopressin, is positively associated with body mass index and risk of type 2 diabetes. Plasma oxytocin is decreased in obesity and several other conditions of abnormal glucose homeostasis. Recent data also show non-classical tissues, such as myocytes, hepatocytes and ß-cells, exhibit responses to oxytocin and vasopressin receptor binding that may contribute to alterations in metabolic function. The modulation of anorexigenic and orexigenic pathways appears to be the dominant mechanism underlying the effects of oxytocin and vasopressin on body weight regulation; however, there are apparent limitations associated with their use in direct pharmacological applications. A clearer picture of their wider physiological effects is needed before either system can be considered for therapeutic use.


Assuntos
Obesidade/metabolismo , Ocitocina/metabolismo , Ocitocina/farmacologia , Vasopressinas/metabolismo , Vasopressinas/farmacologia , Animais , Glicemia , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2 , Ingestão de Alimentos , Metabolismo Energético , Microbioma Gastrointestinal/efeitos dos fármacos , Glucose/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Homeostase/efeitos dos fármacos , Humanos , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Células Musculares/efeitos dos fármacos , Células Musculares/metabolismo , Obesidade/tratamento farmacológico , Ocitocina/sangue , Vasopressinas/sangue
5.
Horm Behav ; 113: 47-54, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31042456

RESUMO

The prairie vole has proven a valuable animal model for the neurobiological study of social monogamy and pair bonding. Previous research has focused almost exclusively on virgin prairie voles forming pair-bonds for the first time - a paradigm with limited relevance to human social behavior. In the present study, we used stud males to assess the impact of repeated pair-bond formation and dissolution on the behaviors and neurobiology relevant to subsequent pair-bond formation. Stud males were tested for behavioral and neurobiological effects of repeated pair-bonding after the 1st, 5th, and 10th pairing. Aged breeder males that experienced minimal pair-bond dissolution were included to control for the effects of aging. Results showed that male prairie voles readily form new pair-bonds after repeated pair-bond dissolution. In terms of social monogamy, old age was associated with males spending less time in close social contact with unfamiliar females. There were no effects of age nor number of lifetime pairings on depressive-like behavior or paternal behavior toward pups. Within the brain, the patterns of oxytocin (OTR) and vasopressin type 1a (V1aR) receptors were largely unaffected, with the following exceptions: 1) males with only a single pairing had higher OTR densities in the paraventricular thalamus and bed nucleus of the stria terminalis; 2) there was an age-related increase in the density of OTR in the caudate putamen and an age-related decline in the density of V1aR in the cortical amygdala. The present findings have translational relevance to human social behavior in the context of aging and social experience.


Assuntos
Envelhecimento/fisiologia , Arvicolinae/fisiologia , Ligação do Par , Maturidade Sexual/fisiologia , Fatores Etários , Animais , Arvicolinae/metabolismo , Encéfalo/metabolismo , Feminino , Masculino , Ocitocina/metabolismo , Comportamento Paterno/fisiologia , Receptores de Ocitocina/metabolismo , Receptores de Vasopressinas/metabolismo , Comportamento Social , Vasopressinas/metabolismo
6.
Life Sci ; 227: 166-174, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31026452

RESUMO

AIMS: To investigate the direct histomorphological clues and observe the biological effects of VP acting on gonadotropin-releasing hormone (GnRH) secretion. MAIN METHODS: Immunofluorescence was conducted to investigate the expressions of GnRH and VP in experimental left varicocele (ELV) rats and ELV repair rats. The colocalization of GnRH and VP was observed by electron microscopy immunohistochemistry. The protein-protein interaction between GnRH and VP was tested by co-immunoprecipitation (co-IP) and the proximity ligation assay (PLA). The effects of intracellular and extracellular VP on GnRH and relative transcription factors (Oct-1, Otx2, Pbx1b and DREAM) were respectively evaluated in VP overexpressed and VP treated GT1-7 cells. KEY FINDINGS: Both hypothalamic GnRH and VP decreased in ELV rats and recovered by ELV repair. The overlapped immunolocalizations of GnRH and VP mainly distributed in the lateral part of the arcuate nucleus (ArcL) and median eminence (ME) with a Manders' overlap coefficient of 0.743 ±â€¯0.117. Immunoreactive substances of GnRH and VP existed in the same and adjacent terminals. VP overexpression did not cause any significant effects on the expressions of GnRH and Oct-1, as well as GnRH promoter activity. While 50-200 pg/ml VP treatments increased GnRH mRNA levels in a dose- and time-dependent manner in GT1-7 cells. Additionally, 200 pg/ml VP triggered a marked promotion of expressions of GnRH, Oct-1, Oxt2 Pbx1b and DREAM, as well as GnRH promoter activity (P < 0.05). SIGNIFICANCE: The results reveal the colocalization and interaction of VP and GnRH, which will be conducive to explain the effects and mechanisms of VP acting on reproduction.


Assuntos
Hormônio Liberador de Gonadotropina/metabolismo , Vasopressinas/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Linhagem Celular , Hormônio Liberador de Gonadotropina/efeitos dos fármacos , Gonadotropinas/metabolismo , Hipotálamo/citologia , Hipotálamo/efeitos dos fármacos , Masculino , Eminência Mediana/metabolismo , Neurônios/metabolismo , Regiões Promotoras Genéticas/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/metabolismo , Vasopressinas/farmacologia
7.
Nature ; 568(7750): 98-102, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30918408

RESUMO

Satiation is the process by which eating and drinking reduce appetite. For thirst, oropharyngeal cues have a critical role in driving satiation by reporting to the brain the volume of fluid that has been ingested1-12. By contrast, the mechanisms that relay the osmolarity of ingested fluids remain poorly understood. Here we show that the water and salt content of the gastrointestinal tract are precisely measured and then rapidly communicated to the brain to control drinking behaviour in mice. We demonstrate that this osmosensory signal is necessary and sufficient for satiation during normal drinking, involves the vagus nerve and is transmitted to key forebrain neurons that control thirst and vasopressin secretion. Using microendoscopic imaging, we show that individual neurons compute homeostatic need by integrating this gastrointestinal osmosensory information with oropharyngeal and blood-borne signals. These findings reveal how the fluid homeostasis system monitors the osmolarity of ingested fluids to dynamically control drinking behaviour.


Assuntos
Encéfalo/fisiologia , Ingestão de Líquidos/fisiologia , Trato Gastrointestinal/fisiologia , Neurônios/fisiologia , Saciação/fisiologia , Sede/fisiologia , Animais , Encéfalo/citologia , Feminino , Neurônios GABAérgicos/metabolismo , Trato Gastrointestinal/inervação , Glutamatos/metabolismo , Masculino , Camundongos , Orofaringe/inervação , Orofaringe/fisiologia , Concentração Osmolar , Prosencéfalo/metabolismo , Nervo Vago/fisiologia , Vasopressinas/metabolismo
8.
Neurochem Res ; 44(5): 1201-1213, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30830595

RESUMO

Reactive oxygen species (ROS) act as signaling molecules for maintaining homeostasis, particularly in the regulation of body-fluid balance in the paraventricular nucleus (PVN) of the hypothalamus. However, there has been little discussion regarding the source of ROS generation in this hypothalamic region. Because iron is the most abundant metal in the brain, we hypothesized that iron may act as a source of ROS, which regulate vasopressin (VP) expression. In the present study, we compared the amount of iron in the PVN to that in other forebrain regions of normal ICR mice, and examined the relationship among iron, ROS, and VP in the PVN of the iron-overloaded with iron dextran and iron-chelated mice with deferoxamine. The amount of iron in the PVN was significantly higher than in any of the forebrain regions we examined. The amount of iron in the PVN was significantly increased in iron-overloaded mice, although not in iron-chelated mice. These results suggest that the PVN exhibits high iron affinity. Both ROS production and VP expression in the PVN of iron-overloaded mice were significantly increased relative to levels observed in control mice. VP concentration in blood of iron-overloaded mice was also significantly higher than that of control mice. Interestingly, iron overload did not alter the expression of nitric oxide synthase, another modulator of VP expression. Taken together, our results suggest that high levels of iron in the PVN induce the production of ROS, which regulate VP expression, independent of nitric oxide signaling.


Assuntos
Ferro/metabolismo , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Hormônio Liberador da Corticotropina/metabolismo , Masculino , Camundongos Endogâmicos ICR , Transdução de Sinais/fisiologia , Vasopressinas/metabolismo
9.
Proc Natl Acad Sci U S A ; 116(12): 5597-5606, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30842287

RESUMO

Oxytocin/vasopressin-like peptides are important regulators of physiology and social behavior in vertebrates. However, the function of inotocin, the homologous peptide in arthropods, remains largely unknown. Here, we show that the level of expression of inotocin and inotocin receptor are correlated with task allocation in the ant Camponotus fellah Both genes are up-regulated when workers age and switch tasks from nursing to foraging. in situ hybridization revealed that inotocin receptor is specifically expressed in oenocytes, which are specialized cells synthesizing cuticular hydrocarbons which function as desiccation barriers in insects and for social recognition in ants. dsRNA injection targeting inotocin receptor, together with pharmacological treatments using three identified antagonists blocking inotocin signaling, revealed that inotocin signaling regulates the expression of cytochrome P450 4G1 (CYP4G1) and the synthesis of cuticular hydrocarbons, which play an important role in desiccation resistance once workers initiate foraging.


Assuntos
Escamas de Animais/metabolismo , Formigas/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Escamas de Animais/crescimento & desenvolvimento , Animais , Hidrocarbonetos , Insetos/metabolismo , Ocitocina/análogos & derivados , Ocitocina/metabolismo , Comportamento Social , Vasopressinas/análise , Vasopressinas/metabolismo , Água/metabolismo
10.
Front Neuroendocrinol ; 53: 100737, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30753840

RESUMO

Vasopressin (AVP) and oxytocin (OXT) regulate social behavior by binding to their canonical receptors, the vasopressin V1a receptor (V1aR) and oxytocin receptor (OTR), respectively. Recent studies suggest that these neuropeptides may also signal via each other's receptors. The extent to which such cross-system signaling occurs likely depends on anatomical overlap between AVP/OXT fibers and V1aR/OTR expression. By comparing AVP/OXT fiber densities with V1aR/OTR binding densities throughout the rat social behavior neural network (SBNN), we propose the potential for cross-system signaling in four regions: the medial amygdala (MeA), bed nucleus of the stria terminalis (BNSTp), medial preoptic area, and periaqueductal grey. We also discuss possible implications of corresponding sex (higher in males versus females) and age (higher in adults versus juveniles) differences in AVP fiber and OTR binding densities in the MeA and BNSTp. Overall, this review reveals the need to unravel the consequences of potential cross-system signaling between AVP and OXT systems in the SBNN for the regulation of social behavior.


Assuntos
Ocitocina/metabolismo , Receptores de Ocitocina/metabolismo , Receptores de Vasopressinas/metabolismo , Comportamento Social , Vasopressinas/metabolismo , Animais , Humanos , Rede Nervosa/metabolismo
11.
eNeuro ; 6(1)2019.
Artigo em Inglês | MEDLINE | ID: mdl-30693316

RESUMO

The neuropeptide arginine vasopressin (AVP) has long been implicated in the regulation of social behavior and communication, but precisely which AVP cell groups are involved is largely unknown. To address whether the sexually dimorphic AVP cell group in the bed nucleus of the stria terminalis (BNST) is important for social communication, we deleted BNST AVP cells by viral delivery of a Cre-dependent caspase-3 cell-death construct in AVP-iCre-positive mice using AVP-iCre negative littermate as controls, and assessed social, sexual, aggressive and anxiety-related behaviors. In males, lesioning BNST AVP cells reduced social investigation of other males and increased urine marking (UM) in the presence of a live female, without altering ultrasonic vocalizations (USVs), resident-intruder aggression, copulatory behavior, anxiety, or investigation of females or their odor cues. In females, which have significantly fewer AVP cells in the BNST, these injections influenced copulatory behavior but otherwise had minimal effects on social behavior and communication, indicating that these cells contribute to sex differences in social behavioral function.


Assuntos
Comunicação Animal , Comportamento Exploratório/fisiologia , Núcleos Septais/fisiologia , Caracteres Sexuais , Comportamento Social , Vasopressinas/metabolismo , Animais , Ansiedade/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Neurônios/fisiologia , Percepção Olfatória/fisiologia , Reprodução/fisiologia
12.
Neuroendocrinology ; 108(3): 190-200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30625474

RESUMO

BACKGROUND/AIMS: Nesfatin-1, processed from nucleobindin-2 (NUCB2), is a potent anorexigenic peptide being expressed in rodent hypothalamic nuclei and involved in the regulation of feeding behavior and body weight in animals. The present study aimed to investigate NUCB2/nesfatin-1 protein expression in the human hypothalamus as well as its correlation with body weight. METHODS: Sections of hypothalamus and adjacent cholinergic basal forebrain nuclei, including the nucleus basalis of Meynert (NBM) and the diagonal band of Broca (DBB), from 25 autopsy cases (17 males, 8 females; 8 lean, 9 overweight, 8 obese) were examined using immunohistochemistry and double immunofluorescence labeling. RESULTS: Prominent NUCB2/nesfatin-1 immunoexpression was detected in supraoptic, paraventricular, and infundibular nuclei, lateral hypothalamic area (LHA)/perifornical region, and NBM/DBB. NUCB2/nesfatin-1 was found to extensively colocalize with (a) oxytocin and vasopressin in paraventricular and supraoptic nuclei, (b) melanin-concentrating hormone in the LHA, and (c) cocaine- and amphetamine-regulated transcript in infundibular and paraventricular nuclei and LHA. Interestingly, in the LHA, NUCB2/nesfatin-1 protein expression was significantly decreased in obese, compared with lean (p < 0.01) and overweight (p < 0.05) subjects. CONCLUSIONS: The findings of the present study are suggestive of a potential role for NUCB2/nesfatin-1 as an integral regulator of food intake and energy homeostasis in the human hypothalamus. In the LHA, an appetite- and reward-related brain area, reduced NUCB2/nesfatin-1 immunoexpression may contribute to dysregulation of homeostatic and/or hedonic feeding behavior and obesity. NUCB2/nesfatin-1 localization in NBM/DBB might imply its participation in the neuronal circuitry controlling cognitive influences on food intake and give impetus towards unraveling additional biological actions of NUCB2/nesfatin-1 in human neuronal networks.


Assuntos
Hormônios Hipotalâmicos/metabolismo , Hipotálamo/metabolismo , Melaninas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Obesidade/metabolismo , Ocitocina/metabolismo , Hormônios Hipofisários/metabolismo , Vasopressinas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Am J Physiol Regul Integr Comp Physiol ; 316(3): R189-R198, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30601706

RESUMO

The purpose of this study was to test the hypothesis that consuming a soft drink (i.e., a high-fructose, caffeinated beverage) during and following exercise in the heat elevates biomarkers of acute kidney injury (AKI) in humans. Twelve healthy adults drank 2 liters of an assigned beverage during 4 h of exercise in the heat [35.1 (0.1)°C, 61 (5)% relative humidity] in counterbalanced soft drink and water trials, and ≥1 liter of the same beverage after leaving the laboratory. Stage 1 AKI (i.e., increased serum creatinine ≥0.30 mg/dl) was detected at postexercise in 75% of participants in the Soft Drink trial compared with 8% in Water trial ( P = 0.02). Furthermore, urinary neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of AKI, was higher during an overnight collection period after the Soft Drink trial compared with Water in both absolute concentration [6 (4) ng/dl vs. 5 (4) ng/dl, P < 0.04] and after correcting for urine flow rate [6 (7) (ng/dl)/(ml/min) vs. 4 (4) (ng/dl)/(ml/min), P = 0.03]. Changes in serum uric acid from preexercise were greater in the Soft Drink trial than the Water trial at postexercise ( P < 0.01) and 24 h ( P = 0.05). There were greater increases from preexercise in serum copeptin, a stable marker of vasopressin, at postexercise in the Soft Drink trial ( P < 0.02) than the Water trial. These findings indicate that consuming a soft drink during and following exercise in the heat induces AKI, likely via vasopressin-mediated mechanisms.


Assuntos
Lesão Renal Aguda/sangue , Biomarcadores , Bebidas Gaseificadas/efeitos adversos , Exercício , Temperatura Alta , Lesão Renal Aguda/fisiopatologia , Adulto , Creatinina/sangue , Ingestão de Líquidos , Feminino , Glicopeptídeos/sangue , Hemodinâmica , Humanos , Lipocalina-2/sangue , Masculino , Vasopressinas/metabolismo , Equilíbrio Hidroeletrolítico , Adulto Jovem
14.
Cell Tissue Res ; 375(1): 259-266, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29961215

RESUMO

Familial neurohypophysial diabetes insipidus (FNDI), characterized by delayed-onset progressive polyuria and loss of arginine vasopressin (AVP) neuron, is an autosomal dominant disorder caused by AVP gene mutations. We previously generated a knock-in mouse model for FNDI, which recapitulated the phenotype of human FNDI. To address the mechanisms underlying AVP neuron loss, we subjected FNDI mice to intermittent water deprivation, which accelerated the phenotype and induced AVP neuron loss within a relative short period. Electron microscopic analyses revealed that aggregates were confined to a sub-compartment of the endoplasmic reticulum (ER), ER-associated compartment (ERAC), in AVP neurons of FNDI mice under normal conditions. In contrast, aggregates scattered throughout the dilated ER lumen, and phagophores, autophagosome precursors, emerged and surrounded the ER containing scattered aggregates in FNDI mice subjected to water deprivation for 4 weeks, suggesting that failure of ERAC formation leads to autophagy induction for degradation of aggregates. Furthermore, the cytoplasm was entirely occupied with large vacuoles in AVP neurons of FNDI mice subjected to water deprivation for 12 weeks, at which stage 30-40% of AVP neurons were lost. Our data demonstrated that although autophagy should primarily be a protective mechanism, continuous autophagy leads to gradual loss of organelles including ER, resulting in autophagy-associated cell death of AVP neurons in FNDI mice.


Assuntos
Autofagia , Diabetes Insípido Neurogênico/metabolismo , Diabetes Insípido Neurogênico/patologia , Neurônios/metabolismo , Neurônios/patologia , Vasopressinas/metabolismo , Animais , Humanos , Ocitocina/metabolismo , Fenótipo
15.
Neurotox Res ; 36(2): 239-256, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30259418

RESUMO

Neuroendocrine and immune signaling pathways are activated following insults such as stress, injury, and infection, in a systemic response aimed at restoring homeostasis. Mitochondrial metabolism and function have been implicated in the control of immune responses. Commonly studied along with mitochondrial function, reactive oxygen species (ROS) are closely linked to cellular inflammatory responses. It is also accepted that cells experiencing mitochondrial or endoplasmic reticulum (ER) stress induce response pathways in order to cope with protein-folding dysregulation, in homeostatic responses referred to as the unfolded protein responses (UPRs). Recent reports indicate that the UPRs may play an important role in immune responses. Notably, the homeostasis-regulating hormones oxytocin (OXT) and vasopressin (AVP) are also associated with the regulation of inflammatory responses and immune function. Intriguingly, OXT and AVP have been linked with ER unfolded protein responses (UPRER), and can impact ROS production and mitochondrial function. Here, we will review the evidence for interactions between these various factors and how these neuropeptides might influence mitochondrial processes.


Assuntos
Imunidade Celular/fisiologia , Mitocôndrias/metabolismo , Ocitocina/metabolismo , Dobramento de Proteína , Vasopressinas/metabolismo , Animais , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Mitocôndrias/imunologia , Ocitocina/imunologia , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Vasopressinas/imunologia
16.
Endocrinology ; 160(1): 38-54, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30364965

RESUMO

Glucocorticoids (GCs) are essential for stress adaptation, acting centrally and in the periphery. Corticotropin-releasing factor (CRF), a major regulator of adrenal GC synthesis, is produced in the paraventricular nucleus of the hypothalamus (PVH), which contains multiple neuroendocrine and preautonomic neurons. GCs may be involved in diverse regulatory mechanisms in the PVH, but the target genes of GCs are largely unexplored except for the CRF gene (Crh), a well-known target for GC negative feedback. Using a genome-wide RNA-sequencing analysis, we identified transcripts that changed in response to either high-dose corticosterone (Cort) exposure for 12 days (12-day high Cort), corticoid deprivation for 7 days (7-day ADX), or acute Cort administration. Among others, canonical GC target genes were upregulated prominently by 12-day high Cort. Crh was upregulated or downregulated most prominently by either 7-day ADX or 12-day high Cort, emphasizing the recognized feedback effects of GC on the hypothalamic-pituitary-adrenal (HPA) axis. Concomitant changes in vasopressin and apelin receptor gene expression are likely to contribute to HPA repression. In keeping with the pleotropic cellular actions of GCs, 7-day ADX downregulated numerous genes of a broad functional spectrum. The transcriptome response signature differed markedly between acute Cort injection and 12-day high Cort. Remarkably, six immediate early genes were upregulated 1 hour after Cort injection, which was confirmed by quantitative reverse transcription PCR and semiquantitative in situ hybridization. This study may provide a useful database for studying the regulatory mechanisms of GC-dependent gene expression and repression in the PVH.


Assuntos
Corticosterona/metabolismo , Genoma , Glucocorticoides/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Transcrição Genética , Animais , Receptores de Apelina/genética , Receptores de Apelina/metabolismo , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Glucocorticoides/genética , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Ratos Wistar , Vasopressinas/genética , Vasopressinas/metabolismo
17.
Neurogastroenterol Motil ; 31(2): e13493, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30334342

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a functional disorder with chronic and relapsing clinical features. Vasopressin (VP) is a hormone responsible for water and stress homeostasis and also regulates gastrointestinal inflammation and motility. We explored whether VP was related to IBD pathogenesis and its possible pathway. METHODS: Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice. The disease activity and colonic damage were evaluated through a scoring system. Locations of the V1a receptor were revealed by immunochemistry method in colon. Ussing chamber technique was performed for the electrophysiological characterization by using rat ileum. The (Arg8 )-Vasopressin (AVP)-evoked short-circuit current (Isc) was recorded in the presence of conivaptan (V1a and V2 receptor antagonist), tolvaptan (V1b receptor antagonist), tetrodotoxin (TTX), atropine, cyclooxygenase (COX) inhibitors (indomethacin, nonspecific COX antagonist; SC560, COX-1 antagonist; NS560, COX-2 antagonist), and a stabilizer of mast cell (cromolyn sodium), respectively. KEY RESULTS: TNBS resulted in the obvious loss of body weight and tissue damages in mice. AVP significantly aggravated the TNBS-induced colitis, which was attenuated by conivaptan but not tolvaptan. V1a receptors were found immunopositive in neurons among the enteric nervous system. AVP evoked a pulsatile response in Isc. Its amplitude, frequency, and cycle duration were around 8-15 µA/cm2 , 10-11 mHz, and 1.5 minutes, respectively. Notably, the AVP-evoked change in Isc was abolished by TTX, atropine, conivaptan, indomethacin, NS560, and cromolyn sodium, respectively. CONCLUSIONS AND INFERENCES: VP-V1a receptor played the proinflammatory role in TNBS-induced colitis by promoting COX-2-dependent prostaglandin release from mucosal mast cells, which was mediated by the cholinergic pathway.


Assuntos
Colite/fisiopatologia , Mastócitos/metabolismo , Receptores de Vasopressinas/metabolismo , Vasopressinas/metabolismo , Animais , Colite/induzido quimicamente , Colite/metabolismo , Ciclo-Oxigenase 2/metabolismo , Sistema Nervoso Entérico/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/metabolismo , Prostaglandinas/metabolismo , Ratos , Ratos Wistar , Ácido Trinitrobenzenossulfônico/toxicidade
18.
Behav Brain Res ; 364: 464-468, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29102591

RESUMO

Social interaction between animals is crucial for the survival and life in groups. It is well demonstrated that oxytocin (OT) and vasopressin (AVP) play critical roles in the regulation of social behaviors in mammals, however, other neurotransmitters and hormones are involved in the brain circuitry related to these behaviors. The present study aimed to investigate the gene expression of neurotransmitter receptors in the brain of OT knockout (OTKO) male mice. In this study, we evaluated the expression levels of the OT receptor (Oxtr), AVP receptors 1a and 1b (Avpr1a; Avpr1b), dopamine receptor 2 (Drd2), and the estrogen receptors alpha and beta (Esr1; Esr2) genes in the hippocampus (HPC), olfactory bulb (OB), hypothalamus (HPT) and prefrontal cortex (PFC). AVP gene (Avp) expression was analyzed in the HPT. Gene expression results were discussed regarding to social interaction and sexual behavior findings. Additionally, we analyzed the influence of OT absence on the Avp mRNA expression levels in the HPT. RNA extraction and cDNAs synthesis followed by quantitative polymerase chain reaction were performed for gene expression determination. Results were calculated with the 2-ΔΔCt method. Our main finding was that HPC is more susceptible to gene expression changes due to the lack of OT. OTKOs exhibited decreased expression of Drd2 and Avpr1b, but increased expression of Oxtr in the HPC. In the PFC, Esr2 was increased. In the HPT, there was a reduced Avp expression in the OTKO group. No differences were detected in the OB and HPT. Despite these changes in gene expression, sexual behavior was not affected. However, OTKO showed higher social investigation and lower aggressive performance than wild-type mice. Our data highlight the importance of OT for proper gene expression of neurotransmitter receptors related to the regulation of social interaction in male mice.


Assuntos
Hipocampo/metabolismo , Relações Interpessoais , Ocitocina/metabolismo , Agressão/fisiologia , Animais , Expressão Gênica/genética , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Knockout , Bulbo Olfatório/metabolismo , Ocitocina/fisiologia , Córtex Pré-Frontal/metabolismo , Receptores de Dopamina D2/genética , Receptores Estrogênicos/genética , Receptores de Ocitocina/genética , Receptores de Ocitocina/metabolismo , Receptores de Vasopressinas/genética , Comportamento Social , Transcriptoma/genética , Vasopressinas/metabolismo
19.
Genes Brain Behav ; 18(1): e12535, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30378258

RESUMO

The role of the hippocampus in social memory and behavior is under intense investigation. Oxytocin (Oxt) and vasopressin (Avp) are two neuropeptides with many central actions related to social cognition. Oxt- and Avp-expressing fibers are abundant in the hippocampus and receptors for both peptides are seen throughout the different subfields, suggesting that Oxt and Avp modulate hippocampal-dependent processes. In this review, we first focus on the anatomical sources of Oxt and Avp input to the hippocampus and consider the distribution of their corresponding receptors in different hippocampal subfields and neuronal populations. We next discuss the behavioral outcomes related to social memory seen with perturbation of hippocampal Oxt and Avp signaling. Finally, we review Oxt and Avp modulatory mechanisms in the hippocampus that may underlie the behavioral roles for both peptides.


Assuntos
Hipocampo/metabolismo , Ocitocina/metabolismo , Aprendizado Social , Vasopressinas/metabolismo , Animais , Hipocampo/fisiologia , Roedores
20.
Am J Surg Pathol ; 43(2): 251-260, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30379651

RESUMO

Tumors of hypothalamic neurons that produce vasopressin are rare. We retrieved all cases of vasopressin-positive tumors in the sellar region from the database of the Department of Pathology. Five cases fulfilled the selection criteria, representing the first series of such tumors. Clinical, radiologic, and pathologic features were reviewed. Four tumors classified as neurocytomas were identified in 3 females and 1 male patient; the ages at onset of symptoms ranged from 17 to 40 years. All were large sellar masses with suprasellar extension and/or invasion of the parasellar sinuses. Three patients had the syndrome of inappropriate antidiuresis; in one of these, a 6-year history was initially considered to be idiopathic. One patient died of progressive disease; 3 had incomplete resections and are being followed. In contrast to these patients with neurocytoma, a 65-year-old woman had Cushing disease and a 0.8 cm mass that was completely resected at transsphenoidal surgery; this tumor was a gangliocytoma producing vasopressin associated with corticotroph hyperplasia. We postulate that the small amount of vasopressin secreted by this mature gangliocytic tumor was locally bound to corticotrophs, resulting in hyperplasia and Cushing disease, without sufficient overproduction to cause systemic effects of vasopressin excess. Hypothalamic neurocytoma is a tumor that can mimic pituitary neuroendocrine tumors and olfactory neuroblastoma but is distinguished by positivity for neurofilaments, NeuN, and TTF-1 and negative staining for adenohypophysial biomarkers. Our cases illustrate that neurocytoma and gangliocytoma are 2 variants of tumors of hypothalamic neurons that can produce vasopressin. The morphologic and proliferative features of these 2 tumor types represent 2 ends of a spectrum; their function also can result in divergent clinical manifestations, one characterized by reduced urine output and the other by the more insidious features of glucocorticoid excess.


Assuntos
Diurese , Ganglioneuroma/patologia , Neoplasias Hipotalâmicas/patologia , Neurocitoma/patologia , Hipersecreção Hipofisária de ACTH/etiologia , Adolescente , Adulto , Idoso , Feminino , Ganglioneuroma/complicações , Humanos , Neoplasias Hipotalâmicas/complicações , Masculino , Neurocitoma/complicações , Vasopressinas/metabolismo
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