La separación materna durante la lactancia altera los niveles basales del sistema neuroendocrino en ratas adolescentes y adultas / Maternal separation during nursing alters basal neuroendocrine levels in juvenile and adult rats

Introducción. En diversos modelos animales, incluido el de la separación materna durante la lactancia, se ha demostrado que las experiencias tempranas adversas, como el maltrato, el abandono materno y el estrés psicosocial, pueden favorecer el desarrollo de algunas enfermedades mentales, pero no se han descrito completamente varios de los cambios que se producen en el sistema neuroendocrino. Objetivo. Determinar si la separación materna durante la lactancia modificaba los niveles basales de neurohormonas como la corticosterona, la corticotropina (ACTH), la oxitocina y la vasopresina (ADH), en ratas jóvenes (35 días) y adultas (90 días). Materiales y métodos. Se separaron ratas Wistar de sus madres durante dos periodos de tres horas diarias a lo largo de los 21 días de lactancia. A los 35 y 90 días se tomaron muestras de los grupos de las ratas de control y de las separadas de la madre, para obtener el suero y posteriormente medir cada una de las hormonas mediante un ensayo inmunoenzimático. Resultados. Las concentraciones de corticosterona fueron mayores en las hembras adultas de control que en el resto de los grupos, y menores en los machos adultos de control. Las de ACTH fueron mayores en los machos y hembras jóvenes separadas de la madre que en los grupos de adultos. Los niveles de oxitocina fueron significativamente mayores en las hembras adultas separadas de la madre que en los otros grupos y significativamente menores en los machos adultos. En cuanto a la vasopresina, los grupos separados de la madre tuvieron concentraciones menores, en comparación con los grupos de jóvenes y adultos de control. Conclusiones. Estos resultados muestran que el estrés temprano al que fueron sometidas las ratas, produjo cambios en las respuestas del eje hipotálamo-hipófisis-suprarrenal, las cuales variaron según el sexo y la edad.

Introduction: Work with different animal models including that of maternal separation during nursing has shown that early adverse experiences such as abuse, maternal abandonment and psychosocial stress may favor the development of various psychopathologies. However, several neuroendocrine changes have not been completely described yet. Objective: To establish whether maternal separation during nursing modifies the basal levels of neurohormones such as corticosterone, ACTH, oxytocin and vasopressin in juvenile and adult rats (aged 35 and 90 days, respectively). Materials and methods: Wistar rats were separated from their mothers for two periods of 3 hours per day during the 21 days of nursing. Once these rats had reached 35 and then 90 days of age, blood samples were taken from both the separated and control groups to obtain serum for immunoenzymatic assays and measure the levels of each of the hormones. Results: Concentrations of corticosterone were higher in control adult females in comparison with the rest of the groups and lower in the control adult males. Those of ACTH were higher in the separated young males and females than in the adult groups. Oxytocin levels were significantly higher in the separated adult females in comparison with the other groups and significantly lower in the adult males. With respect to vasopressin, the separated groups had lower concentrations than the young and adult control groups. Conclusions: These results show that the early stress to which rats were submitted produced changes in the basal responses of the hypothalamic-pituitary-adrenal axis, that these responses were distinct in males and females and that they also differed according to age.

Central actions of glucocorticoids in the control of body fluid homeostasis: review

The involvement of the hypothalamic-pituitary-adrenal axis in the control of body fluid homeostasis has been extensively investigated in the past few years. In the present study, we reviewed the recent results obtained using different approaches to investigate the effects of glucocorticoids on the mechanisms of oxytocin and vasopressin synthesis and secretion in response to acute and chronic plasma volume and osmolality changes. The data presented here suggest that glucocorticoids are not only involved in the mechanisms underlying the fast release but also in the transcriptional events that lead to decreased synthesis and secretion of these neuropeptides, particularly oxytocin, under diverse experimental conditions of altered fluid volume and tonicity. The endocannabinoid system, through its effects on glutamatergic neurotransmission within the hypothalamus and the nuclear factor κB-mediated transcriptional activity, seems to be also involved in the specific mechanisms by which glucocorticoids exert their central effects on neurohypophyseal hormone synthesis and secretion.

GABA in the central amygdaloid nucleus modulates the electrolyte excretion and hormonal responses to blood volume expansion in rats

We investigated the involvement of GABAergic mechanisms of the central amygdaloid nucleus (CeA) in unanesthetized rats subjected to acute isotonic or hypertonic blood volume expansion (BVE). Male Wistar rats bearing cannulas unilaterally implanted in the CeA were treated with vehicle, muscimol (0.2 nmol/0.2 µL) or bicuculline (1.6 nmol/0.2 µL) in the CeA, followed by isotonic or hypertonic BVE (0.15 or 0.3 M NaCl, 2 mL/100 g body weight over 1 min). The vehicle-treated group showed an increase in sodium excretion, urinary volume, plasma oxytocin (OT), and atrial natriuretic peptide (ANP) levels compared to control rats. Muscimol reduced the effects of BVE on sodium excretion (isotonic: 2.4 ± 0.3 vs vehicle: 4.8 ± 0.2 and hypertonic: 4.0 ± 0.7 vs vehicle: 8.7 ± 0.6 µEq·100 g-1·40 min-1); urinary volume after hypertonic BVE (83.8 ± 10 vs vehicle: 255.6 ± 16.5 µL·100 g-1·40 min-1); plasma OT levels (isotonic: 15.3 ± 0.6 vs vehicle: 19.3 ± 1 and hypertonic: 26.5 ± 2.6 vs vehicle: 48 ± 3 pg/mL), and ANP levels (isotonic: 97 ± 12.8 vs vehicle: 258.3 ± 28.1 and hypertonic: 160 ± 14.6 vs vehicle: 318 ± 16.3 pg/mL). Bicuculline reduced the effects of isotonic or hypertonic BVE on urinary volume and ANP levels compared to vehicle-treated rats. However, bicuculline enhanced the effects of hypertonic BVE on plasma OT levels. These data suggest that CeA GABAergic mechanisms are involved in the control of ANP and OT secretion, as well as in sodium and water excretion in response to isotonic or hypertonic blood volume expansion.

Social stimuli cause changes of plasma oxytocin and behavior in guinea pigs

The neuropeptide oxytocin (OXT) is a key factor in the initiation and regulation of sociosexual behavior. The present study analyzes the effects of cohabitation and social challenge on plasma OXT concentration rates in guinea pig pairs in relation to male sociosexual behavior. The cohabitation phase lasted 3 days. On day 4, the pair was socially challenged by introducing an unfamiliar male. Displayed male sexual behavior varied significantly during cohabitation, with peaks on day 1. Sociopositive behavior, i.e., side-by-side contact, was increased on days 3 and 4. Cohabitation per se led to elevated plasma OXT concentrations only in males. In contrast, both sexes reacted with increased plasma OXT concentrations to the social challenge (day 4). At that time, male OXT was significantly correlated with sexual behavior and female OXT with sociosexual behavior received from the partner. Additionally, pairs were synchronized in their OXT release during days 3 and 4. We conclude that cohabitation causes sexually dimorphic plasma OXT concentration patterns in guinea pigs. Secondly, the conformity of OXT release in both sexes may represent an endocrine marker for long-term cohabitation, which is reflected behaviorally by increased spatial proximity.

Role of oxytocin as regulator of leptin secretion and its relation to biochemical markers [OPG and SRANKL] of bone resorption and formation

Increasing evidences demonstrated many new targets for the hypothalamic hormone oxytocin [OT] supporting the presence of a central neuroendocrine and/or humoral factors that control bone remodeling. The present study was carried out to test the effect of OT on serum leptin level and on the regulation of skeletal homeostasis through measurement of serum levels of osteoprotogerin OPG [secreted glycoprotein of the tumour necrosis receptor superfamily], sRANKL [soluble decoy receptor activator of nuclear factor kappa filigand], calcium and phosphorus. Fifty adult male albino rats used in this study. They were divided into three groups: group I which was subdivided into 3 subgroups, subgroup IA untreated control, IB injected with DM SO [0.16 ml/kg, b.wt x 6 weeks], 1C injected with DMSO [0.08 ml/kg b.wt for 12 weeks]. II OT treated [40 micro/kg b.wt x6 weeks] group. Ill OT [8 micro/kg b.wt x 12 weeks] group. The results obtained showed very high significant increase in OPG level in group [II] compared with subgroups I A and IB and high significant increase of OPG in group [III] compared with subgroup 1C. On the other hand, non significant change was detected in serum levels of sRANKL. As regards serum leptin, a high significant increase was found in group II as compared with subgroups IA and IB and a high significant increase was detected in group [III] compared with IA and 1C subgroups. Serum calcium and phosphorus levels showed very high significant decrease in group [II] compared with IA and IB subgroups and high significant decrease in group [HI] compared with subgroup IA. Also, significant increase in OPG/sRANKL ratio in group [II] compared with IA subgroup. A negative correlation between sRANKL and OPG/sRANKL ratio was obtained in both OT treated groups.The OPG and sRANKL levels obtained in OT treated rats favor increased osteoblast over osteoclast activity and may explain, in part, the imbalance in bone remodeling in favor of bone formation. 'The rise in OPG serum level is probably a homeostatic mechanism to limit bone loss. We can say that leptin should be reappraised as an indicator of energy supplies available for homeostasis, which now includes bone remodeling. We can conclude that the stimulating effect of OT on serum leptin together with increased OPG synthesis indicate anabolic effect on osteoblastic cells to support bone formation and indicate the important role of OPG in bone remodeling and it may be useful for the treatment of osteoporosis associated with increased osteoclast function. OT and leptin can now be added to the array of bone modulating signalling molecules

Efeitos da analgesia do sufentanil por via subracnóidea e bupivacaína a 0.25 por cento por via peridural sobre as concentraçöes plasmáticas de ocitocina e cortisol em gestantes em trabalho de parto / Effects of analgesic intrathecal sufentanil and 0.25 por cento epidural bupivacaine on oxytocin and cortisol plasma concentration in labor patients

Justificativa e Objetivos: O sufentanil por via subracnóidea promove analgesia do trabalho de parto comparável à peridural com anestésicos locais. As duas técnicas diminuem alguns parâmetros da resposta neuroendócrina à dor do parto, e ambas podem atenuar a liberaçäo reflexa de ocitocina em animais. O objetivo deste estudo foi comparar os efeitos das duas técnicas nas concentraçöes plasmáticas de ocitocina (CPO) e cortisol (CPC) durante o trabalho de parto. Método: Trinta parturientes com 4 - 7 cm de dilataçäo foram arroladas neste estudo de forma aleatória e encoberta. No grupo S receberam sufentanil (10 µg) por via peridural. A Analgesia foi medida usando Escala Analógica Visual e amostras sangüineas de ocitocina e cortisol foram obtidas antes, 30 e 60 minutos após a administraçäo das drogas. As CPO e CPC foram determinadas através da técnica de radioimunoensaio. Resultados: A analgesia no grupo S foi mais intensa aos 30 minutos. As CPO e CPC nos dois grupos foram semelhantes antes da analgesia. No grupo S, houve diminuiçäo significativa da CPO aos 60 minutos e CPC aos 30 e 60 minutos, enquanto no grupo B, CPO e CPC permaneceram estáveis durante todo o estudo. Conclusöes: Nas condiçöes deste estudo, a analgesia peridural com bupivacaína esteve associada à manutençäo das concentraçöes plamáticas de cortisol e ocitocina. Contrariamente, a analgesia promovida pelo sufentanil, por via subracnóidea, foi mais intensa e produziu diminuiçäo nas concentraçöes destes hormônios

Inativaçäo da ocitocina sintética pelo plasma total de gestantes normais a termo / Synthetic oxytocin inactivation by total plasma of normal and at term pregnant women

Tentou-se verificar se o plasma de gestantes normais a termo (uma a duas semanas antes do trabalho de parto) promovia a inativaçäo da ocitocina sintética (Syntocinon Sandoz), quando incubada com o mesmo. Para isto, foi utilizado o plasma de 14 mulheres grávidas normais, fazendo-se paralelamente um grupo-controle constituído por 3 homens e 3 mulheres näo-gestantes. Uma vez obtida as amostras, estas foram incubadas com ocitocina sintética em banho maria a 37-C por 5 minutos, após o que foram testadas sobre útero isolado de rata pelo método da superfusäo. De acordo com os resultados obtidos, concluiu-se que o plasma de gestantes a termo, inativa 51,3% da ocitocina sintética adicionada ao meio de incubaçäo, enquanto o plasma de homens e näo-gestantes näo apresenta nenhuma açäo inativadora sobre o ocitocina