RESUMO

Introduction: The medial preoptic area (mPOA) participates in thermoregulatory control and blood pressure modulation as shown by studies with electrical stimulation of this area or cobalt chloride injection, a non-selective synapse inhibitor. This study aimed to investigate whether angiotensin II (Ang II) and GABA could act or not in the mPOA to mediate the cardiovascular and micturition control pathways. Methods: Female Wistar rats were submitted to stereotaxic surgery for implantation of a guide cannula into the mPOA 7 days prior to the experiments. Afterwards, the animals were isoflurane- anesthetized and submitted to the catheterization of the femoral artery and vein and urinary bladder cannulation for mean arterial pressure (MAP), heart rate (HR), and intravesical pressure (IP) recordings, respectively. After the baseline MAP, HR, and IP recordings for 15 min, Ang II (0.1 nM, 1 µL), losartan (AT-1 receptor antagonist, 100 nM, 1 µL), GABA (50 mM, 1 µL) or saline (1 µL) were injected into the mPOA, and the variables were measured for additional 30 min. In a different group of rats, the AT-1 receptor, angiotensin II converting enzyme (ACE), and GABAa receptor gene expression was evaluated in mPOA samples by qPCR. The data are as mean ± SEM and submitted to One-way ANOVA (Tukey posttest) or paired Student t-test (P <0.05). Results: The injection of Ang II into the mPOA evoked a significant hypotension (-37±10 mmHg, n = 6, p = 0.024) and bradycardia (-47 ± 20 bpm, p = 0.030) compared to saline (+1 ± 1 mmHg and +6 ± 2 bpm, n = 6). A significant increase in IP was observed after Ang II injection into the mPOA (+72.25 ± 17.91%, p = 0.015 vs. -1.80 ± 2.98%, n = 6, saline). No significant changes were observed in MAP, HR and IP after the losartan injection in the mPOA compared to saline injection. Injection of GABA into the mPOA evoked a significant fall in MAP and HR (-68 ± 2 mmHg, n = 6, p < 0.0001 and -115 ± 14 bpm, n = 6, p = 0.0002 vs. -1 ± 1 mmHg and +4 ± 2 bpm, n = 6, saline), but no significant changes were observed in IP. The AT-1 receptor, ACE and GABAa receptor mRNA expression was observed in all mPOA samples. Discussion: Therefore, in female rats, Ang II mediated transmission in the mPOA is involved in the cardiovascular regulation and in the control of central micturition pathways. A phasic control dependent on AT-1 receptors in the mPOA seems to be involved in the regulation of those cardiovascular and intravesical 3 parameters. In contrast, GABAergic transmission in the mPOA participates in the pathways of cardiovascular control in anesthetized female rats, nevertheless, this neurotransmission is not involved in the micturition control.

RESUMO

The postpartum period is a demanding time during which mothers experience numerous physiological adaptations that enable them to care for their offspring while maintaining their wellbeing. Hypocretins, also known as orexins, are neuropeptides synthesized by hypothalamic neurons that play a fundamental role in several functions, including the promotion of wakefulness and motivated behaviors, such as maternal care. In this regard, several findings suggest that the activity of the hypocretinergic system increases in the early postpartum period and begins to decline as weaning approaches. In particular, hypocretins within the medial preoptic area, a crucial region during this period, modulate both maternal behavior and sleep. Although further studies are necessary to obtain a comprehensive understanding of the role of hypocretins in lactating females, current research suggests that this system participates in promoting active components of maternal behavior and regulating wakefulness and sleep adjustments during the postpartum period, potentially leading to increased wakefulness during this stage. These adaptive adjustments enable the mother to cope with the continuously changing demands of the pups.

RESUMO

Among the different species of mammals, the expression of maternal behavior varies considerably, although the end points of nurturance and protection are the same. Females may display passive or active responses of acceptance, recognition, rejection/fear, or motivation to care for the offspring. Each type of response may indicate different levels of neural activation. Different natural stimuli can trigger the expression of maternal and paternal behavior in both pregnant or virgin females and males, such as hormone priming during pregnancy, vagino-cervical stimulation during parturition, mating, exposure to pups, previous experience, or environmental enrichment. Herein, we discuss how the olfactory pathways and the interconnections of the medial preoptic area (mPOA) with structures such as nucleus accumbens, ventral tegmental area, amygdala, and bed nucleus of stria terminalis mediate maternal behavior. We also discuss how the triggering stimuli activate oxytocin, vasopressin, dopamine, galanin, and opioids in neurocircuitries that mediate acceptance, recognition, maternal motivation, and rejection/fear.

Assuntos

Audição

RESUMO

Hypoxic-ischemic encephalopathy is a severe clinical condition, among others, affecting the brain after offspring exposure to neonatal anoxia, which causes persistent sensorimotor and cognitive deficits. During peripartum, maternal behaviors are crucial for the healthy development of the offspring. In rats, the vocalization of newborns, around 40 kHz, corresponds to separation calls that encourage their mothers to retrieve them. Alterations in this pattern affect the maternal behavior addressed to the offspring. This study aimed to evaluate the maternal behavior of primiparous rats whose offspring were exposed to neonatal anoxia in P2 (postpartum day) during the lactation period, to assess mother-pup interactions through the pups' vocalization from P3 to P18. It also intends to quantify eventual neuronal alterations in the mothers' medial preoptic area after the last weaning (P21) through FOS protein expression. Anoxia offspring were found to reduce maternal behaviors toward them, increased frequency of separation calls in the male anoxia group, and reduced vocalization rate in the female anoxia group compared to their respective controls. Body weight gain reduction of males' and females' anoxia was observed. We concluded that anoxia exerts deleterious effects on the vocalization patterns of the pups, with sex differences that alter maternal behavior toward them. Impaired USV makes an additional negative impact on the already noxious effects of neonatal anoxia. Understanding those phenomena applies/contributes to guiding procedures and strategies to mitigate the deleterious outcomes and orient research concerning the complexity of neonatal anoxia events and the influence of maternal care quality concerning the pups, which should also be considered sex differences.

Assuntos

Comportamento Materno , Vocalização Animal , Humanos , Ratos , Animais , Feminino , Masculino , Vocalização Animal/fisiologia , Mães , Lactação , Hipóxia , Animais Recém-Nascidos

RESUMO

The medial preoptic area (mPOA) undergoes through neuroanatomical changes across the postpartum period, during which its neurons play a critical role in the regulation of maternal behavior. In addition, this area is also crucial for sleep-wake regulation. We have previously shown that hypocretins (HCRT) within the mPOA facilitate active maternal behaviors in postpartum rats, while the blockade of endogenous HCRT in this area promotes nursing and sleep. To explore the mechanisms behind these HCRT actions, we aimed to evaluate the effects of juxta-cellular HCRT-1 administration on mPOA neurons in urethane-anesthetized postpartum and virgin female rats. We recorded mPOA single units and the electroencephalogram (EEG) and applied HCRT-1 juxta-cellular by pressure pulses. Our main results show that the electrophysiological characteristics of the mPOA neurons and their relationship with the EEG of postpartum rats did not differ from virgin rats. Additionally, neurons that respond to HCRT-1 had a slower firing rate than those that did not. In addition, administration of HCRT increased the activity in one group of neurons while decreasing it in another, both in postpartum and virgin rats. This study suggests that the mechanisms by which HCRT modulate functions controlled by the mPOA involve different cell populations.

Assuntos

Lactação , Área Pré-Óptica , Animais , Feminino , Neurônios/fisiologia , Orexinas/farmacologia , Ratos , Uretana

RESUMO

In normal hormonal conditions, increased neuronal activity in the ventromedial hypothalamus (VMH) induces lordosis whereas activation of the preoptic area (POA) exerts an opposite effect. In the present work, we explored the effect of bilateral infusion of different doses of the apelin-13 (0.37, 0.75, 1.5, and 15 µg) in both brain areas on the expression of lordosis behavior. Lordosis quotient and lordosis reflex score were performed at 30, 120, and 240 min. Weak lordosis was observed following the 0.37 µg dose of apelin-13 at 30 min in the VMH of EB-primed rats; however, the rest of the doses induced significant lordosis relative to the control group. At 120 min, all doses induced lordosis behavior, while at 240 min, the highest dose of 15 µg did not induce significant differences. Interestingly, only the 0.75 µg infusion of apelin in the POA induced significant lordosis at 120 and 240 min. These results indicate that apelin-13 acts preferably in HVM and slightly in POA to initiate lordosis behavior in estrogen-primed rats.

Assuntos

Peptídeos e Proteínas de Sinalização Intercelular , Lordose , Área Pré-Óptica , Animais , Estradiol/farmacologia , Estrogênios/farmacologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/patologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Lordose/induzido quimicamente , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/patologia , Progesterona/farmacologia , Ratos , Comportamento Sexual Animal/efeitos dos fármacos , Núcleo Hipotalâmico Ventromedial/efeitos dos fármacos , Núcleo Hipotalâmico Ventromedial/patologia

RESUMO

Temporal coordination of organisms according to the daytime allows a better performance of physiological processes. However, modern lifestyle habits, such as food intake during the rest phase, promote internal desynchronization and compromise homeostasis and health. The hypothalamic suprachiasmatic nucleus (SCN) synchronizes body physiology and behavior with the environmental light-dark cycle by transmitting time information to several integrative hypothalamic nuclei, such as the paraventricular nucleus (PVN), dorsomedial hypothalamic nucleus (DMH) and median preoptic area (MnPO). The SCN receives metabolic information mainly via Neuropeptide Y (NPY) inputs from the intergeniculate nucleus of the thalamus (IGL). Nowadays, there is no evidence of the response of the PVN, DMH and MnPO when the animals are subjected to internal desynchronization by restricting food access to the rest phase of the day. To explore this issue, we compared the circadian activity of the SCN, PVN, DMH and MnPO. In addition, we analyzed the daily activity of the satiety centers of the brainstem, the nucleus of the tractus solitarius (NTS) and area postrema (AP), which send metabolic information to the SCN, directly or via the thalamic intergeniculate leaflet (IGL). For that, male Wistar rats were assigned to three meal protocols: fed during the rest phase (Day Fed); fed during the active phase (Night Fed); free access to food (ad libitum). After 21 d, the daily activity patterns of these nuclei were analyzed by c-Fos immunohistochemistry, as well as NPY immunohistochemistry, in the SCN. The results show that eating during the rest period produces a phase advance in the activity of the SCN, changes the daily activity pattern in the MnPO, NTS and AP and flattens the c-Fos rhythm in the PVN and DMH. Altogether, these results validate previous observations of circadian dysregulation that occurs within the central nervous system when meals are consumed during the rest phase, a behavior that is involved in the metabolic alterations described in the literature.

Assuntos

Ritmo Circadiano , Hipotálamo , Animais , Masculino , Ratos , Ritmo Circadiano/fisiologia , Hipotálamo/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Núcleo Supraquiasmático/metabolismo

RESUMO

Central micturition control and urine storage involve a multisynaptic neuronal circuit for the efferent control of the urinary bladder. Electrical stimulation of the lateral preoptic area (LPA) at the level of the decussation of the anterior commissure in cats evokes relaxation of the bladder, whereas ventral stimulation of LPA evokes vigorous contraction. Endogenous Angiotensin-(1-7) [(Ang-(1-7)] synthesis depends on ACE-2, and its actions on binding to Mas receptors, which were found in LPA neurons. We aimed to investigate the Ang-(1-7) actions into the LPA on intravesical pressure (IP) and cardiovascular parameters. The gene and protein expressions of Mas receptors and ACE-2 were also evaluated in the LPA. Angiotensin-(1-7) (5 nmol/µL) or A-779 (Mas receptor antagonist, 50 nmol/µL) was injected into the LPA in anesthetized female Wistar rats; and the IP, mean arterial pressure (MAP), heart rate (HR), and renal conductance (RC) were recorded for 30 min. Unilateral injection of Ang-(1-7) into the LPA increased IP (187.46 ± 37.23%) with peak response at ∼23-25-min post-injection and yielded no changes in MAP, HR, and RC. Unilateral or bilateral injections of A-779 into the LPA decreased IP (-15.88 ± 2.76 and -27.30 ± 3.40%, respectively) and elicited no changes in MAP, HR, and RC. The genes and the protein expression of Mas receptors and ACE-2 were found in the LPA. Therefore, the LPA is an important part of the circuit involved in the urinary bladder control, in which the Ang-(1-7) synthetized into the LPA activates Mas receptors for increasing the IP independent on changes in RC and cardiovascular parameters.

RESUMO

This work evaluated the effects of neonatal overfeeding, induced by litter size reduction, on fertility and the noradrenaline-kisspeptin-gonadotrophin releasing hormone (GnRH) pathway in adult female rats. The litter size was adjusted to 3 pups with each mother in the small litters (SL) and 10 pups with each mother in the normal litters (NL). SL females exhibited metabolic changes associated with reproductive dysfunctions, shown by earlier vaginal opening and first estrus, later regular cyclicity onset, and lower and higher occurrences of estrus and diestrus phases, respectively, as well as reduced fertility, estradiol plasma levels, and mRNA expressions of tyrosine hydroxylase in the locus coeruleus, kisspeptin, and GnRH in the preoptic area in adult females in the afternoon of proestrus. These results suggest that neonatal overfeeding in female rats promotes reproductive dysfunctions in adulthood, such as lower estradiol plasma levels associated with impairments in fertility and noradrenaline-kisspeptin-GnRH pathway during positive feedback.

Assuntos

Envelhecimento/fisiologia , Estradiol/sangue , Fertilidade/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Kisspeptinas/metabolismo , Norepinefrina/metabolismo , Hipernutrição/sangue , Hipernutrição/metabolismo , Animais , Animais Recém-Nascidos , Glicemia/metabolismo , Tronco Encefálico/patologia , Ciclo Estral , Feminino , Hormônio Liberador de Gonadotropina/genética , Gônadas/patologia , Hipotálamo/patologia , Lipídeos/sangue , Tamanho da Ninhada de Vivíparos , Masculino , Hipófise/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Maturidade Sexual , Aumento de Peso

RESUMO

This study aimed to evaluate the physical exercise-induced neuronal activation in brain nuclei controlling thermoregulatory responses in hypertensive and normotensive rats. Sixteen-week-old male normotensive Wistar rats (NWRs) and spontaneously hypertensive rats (SHRs) were implanted with an abdominal temperature sensor. After recovery, the animals were subjected to a constant-speed treadmill running (at 60% of the maximum aerobic speed) for 30 min at 25 °C. Core (Tcore) and tail-skin (Tskin) temperatures were measured every minute during exercise. Ninety minutes after the exercise, the rats were euthanized, and their brains were collected to determine the c-Fos protein expression in the following areas that modulate thermoregulatory responses: medial preoptic area (mPOA), paraventricular hypothalamic nucleus (PVN), and supraoptic nucleus (SON). During treadmill running, the SHR group exhibited a greater increase in Tcore and an augmented threshold for cutaneous heat loss relative to the NWR group. In addition, the SHRs showed reduced neuronal activation in the mPOA (< 49.7%) and PVN (< 44.2%), but not in the SON. The lower exercise-induced activation in the mPOA and PVN in hypertensive rats was strongly related to the delayed onset of cutaneous heat loss. We conclude that the enhanced exercise-induced hyperthermia in hypertensive rats can be partially explained by a delayed cutaneous heat loss, which is, in turn, associated with reduced activation of brain areas modulating thermoregulatory responses.

Assuntos

Regulação da Temperatura Corporal , Hipertensão/fisiopatologia , Hipotálamo/fisiopatologia , Corrida , Animais , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Wistar

RESUMO

Leptin mediates the interaction between reproductive function and energy balance. However, leptin receptors are not expressed in neurons that produce gonadotropin-releasing hormone (GnRH), likely indicating an indirect action through interneurons. Among likely neurons that modulate the secretion of GnRH are NO (nitric oxide) neurons. We assessed whether estradiol and feeding conditions modulate a possible interaction between leptin and NO in brain areas related to the control of reproductive function. Estradiol-treated and untreated ovariectomized rats were normally fed or fasted for 48 h. Then, saline (control) or leptin (3 µg/1 µl) intracerebroventricular microinjections were administered, and after thirty minutes, the brains collected subsequent to the decapitation or transcardially perfusion. Leptin and estradiol increased NO synthase (nNOS) gene expression (RT-PCR) and content (Western blotting) in the medial preoptic area (MPOA) and medial basal hypothalamus (MBH) only in fasted rats. Leptin increased: 1-phosphorylated-signal transducer and activator of transcription-3(pSTAT3) (immunohistochemistry) in the MPOA and various hypothalamic nuclei [arcuate (ARC); ventromedial (VMH); dorsal/ventral dorsomedial (dDMH/vDMH); premammilar ventral (PMV)], effects potentiated by estradiol/fasting interaction; 2- nNOS/pSTAT3 coexpression in the MPOA only in estradiol-treated, fasted rats; 3- nNOS-immunoreactive cell expression in the VMH, DMH and PMV (areas related to reproductive function control) of estradiol -treated rats. Thus, when leptin is reduced during fasting, leptin replacement effectively increased the expression of nitric oxide, which activated the HPG axis only in the presence of estradiol. Estradiol modulates the nitrergic system, leptin sensitivity and consequently leptin's effects on the nitrergic system in hypothalamus and in particular vDMH and PMV.

Assuntos

Estradiol/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Leptina/metabolismo , Neurônios/metabolismo , Animais , Feminino , Hipotálamo/metabolismo , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/metabolismo , Ratos , Receptores para Leptina/metabolismo , Fator de Transcrição STAT3/metabolismo

RESUMO

The involvement of brainstem noradrenergic system in thermoregulation during exercise was evaluated by assessing the neuronal activation of A1, A2, locus coeruleus (LC) during exercise. Male Wistar rats weighing 280-330 g were used in the present study. Ninety minutes after exercise bout until fatigue, animals were anaesthesiated and brain removed and processed immunohistochemically for Fos protein and tyrosine hydroxylase in A1, A2 and LC and for Fos in POA subregions. Core and tail temperature were recorded during all running period by telemetry system. Heat storage rate (HSR, cal.min-1), maximum tail vasoconstriction (°C) and vasodilatation threshold (°C) were calculated and correlated with Fos expression in all nuclei studied. Fos expression in LC correlated inversely with maximum tail skin vasoconstriction (r = -0.787, p < 0.03) and HSR (r = -0.834, p < 0.02) and positively to time to fatigue (r = 0.862, p < 0.01). A1 nucleus showed an inverse correlation with tail skin vasodilatation threshold (r = -0.861, p < 0.01). Fos expression in LC correlated inversely with Fos expression in the median (MnPO, r = -0.909, p < 0.01) and medial preoptic nucleus (MPOM, r = -0.942, p < 0.05). Our results bring further evidences that noradrenergic neurons from LC and A1 nuclei are involved in cutaneous heat loss mechanisms during exercise. LC nucleus probably modulates the sympathetic tonus of tail artery and integrates the central network LC / POA that could represent an important circuitry of temperature regulation during exercise. Also, noradrenergic neurons from A1 nucleus could be involved in cutaneous heat loss during exercise by modulating of vasodilatation threshold.

Assuntos

Neurônios Adrenérgicos/metabolismo , Regulação da Temperatura Corporal/fisiologia , Tronco Encefálico/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Masculino , Norepinefrina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Tirosina 3-Mono-Oxigenase/metabolismo

RESUMO

Ibuprofen, a non-steroidal anti-inflammatory drug, inhibits the activity of cyclooxygenase enzyme, leading to reduction in Prostaglandin E2 (PGE2) production. Due to the importance of PGE2 in promoting the brain masculinization in male fetus, this study aimed to evaluate the effects of in utero and lactational exposure to ibuprofen and their late repercussions on reproductive parameters in male rats. Pregnant rats were exposed to ibuprofen (10, 30 or 60 mg/kg) or vehicle (control group) per gavage daily from gestational day 15 to day 21 after birth, and late reproductive effects were assessed during the sexual development and in the reproductive adult life in the male offspring. Males exposed to ibuprofen had a decrease in body weight and anogenital distance, as well as a delay in the ages of testicular descent and preputial separation. In adulthood, there was a decrease in the Leydig cells nuclei volume, testosterone levels and percentage of normal sperm morphology. All animals exposed to ibuprofen presented male copulatory behavior, however, in the presence of another male, they also presented a female-typical behavior. Maternal exposure to ibuprofen during the sensitive windows of brain development adversely impacted the reproductive parameters of male rats, suggesting an incomplete masculinization of the hypothalamus.

Assuntos

Encéfalo/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Ibuprofeno/efeitos adversos , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Diferenciação Sexual/efeitos dos fármacos , Animais , Feminino , Ibuprofeno/administração & dosagem , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Ratos , Ratos Wistar

RESUMO

Parental provisioning of offspring with physiological products (nursing) occurs in many animals, yet little is known about the neuroendocrine basis of nursing in non-mammalian species. Within amphibians, maternal provisioning has evolved multiple times, with mothers of some species feeding unfertilized eggs to their developing offspring until tadpoles complete metamorphosis [1-3]. We conducted field studies in Ecuador and Madagascar to ask whether convergence at the behavioral level provides similar benefits to offspring and relies on shared neural mechanisms in dendrobatid and mantellid poison frogs. At an ecological level, we found that nursing allows poison frogs to provide chemical defenses to their tadpoles in both species. At the neural level, nursing was associated with increased activity in the lateral septum and preoptic area, demonstrating recruitment of shared brain regions in the convergent evolution of nursing within frogs and across vertebrates [4]. In contrast, only mantellids showed increased oxytocin neuron activity akin to that in nursing mammals [5], suggesting evolutionary versatility in molecular mechanisms. Our findings demonstrate that maternal provisioning provides similar potential benefits to offspring and relies on similar brain regions in poison frog species with convergently evolved toxicity and maternal care. VIDEO ABSTRACT.

Assuntos

Anuros/fisiologia , Encéfalo/fisiologia , Comportamento Materno , Alcaloides/metabolismo , Animais , Anuros/crescimento & desenvolvimento , Equador , Larva/crescimento & desenvolvimento , Larva/fisiologia , Madagáscar , Óvulo

RESUMO

Social behavior exhibits a wide diversity among vertebrates though it is controlled by a conserved neural network, the social behavior network (SBN). The activity of the SBN is shaped by hypothalamic nonapeptides of the vasopressin-oxytocin family. The weakly electric fish Brachyhypopomus gauderio emits social electrical signals during courtship. Three types of vasotocin (AVT) cells occur in the preoptic area (POA), one of the SBN nodes. In this study, we aimed to test if POA neurons of the nucleus preopticus ventricularis anterior (PPa) and posterior (PPp), and in particular AVT+ cells, were activated by social stimuli using a 2-day behavioral protocol. During the first night, male-female dyads were recorded to identify courting males. During the second night, these males were divided in two experimental conditions: isolated and social (male with a female). Both AVT cells and the cellular activation of the POA neurons (measured by FOS) were identified. We found that the PPa of social males showed more FOS+ cells than the PPa of isolated males, and that the PPa had more AVT+ cells in social males than in isolated males. The double-immunolabeling for AVT and FOS indicated the activation of AVT+ neurons. No significant differences in the activation of AVT+ cells were found between conditions, but a clear association was observed between the number of AVT+ cells and certain behavioral traits. In addition, a different activation of AVT+ cell-types was observed for social vs. isolated males. We conclude that the POA of B. gauderio exhibits changes induced by social stimuli in reproductive context, involving an increase in AVT production and a different profile activation among AVT+ cell populations.

RESUMO

Although the melanin-concentrating hormone (MCH) and its coding mRNA are predominantly found in the tuberal hypothalamus, there is detectable synthesis of MCH in the preoptic hypothalamus exclusively in lactating dams, suggesting a participation of MCH in the alterations that take place after parturition. Also implicated in the dam physiology is oxytocin, a neurohormone released from the posterior pituitary that is necessary for milk ejection. Because the projection fields from oxytocin-immunoreactive (-IR) neurones and the mediobasal preoptic hypothalamus overlap and MCH-IR neurones are found in proximity to oxytocin neurones, we investigated the spatial relationship between MCH and oxytocin fibres. Accordingly, we employed multiple immunohistochemistry labelling for MCH and oxytocin for light and electron microscopy techniques, in addition to i.v. tracer injection combined with in situ hybridisation to identify MCH neurones that project to neurosecretory areas. As described for other strains, lactating Long-Evans dams also display immunoreactivity for MCH in the preoptic hypothalamus on days 12 and 19 of lactation. The appearance of these neurones is contemporaneous with an increase in MCH-IR fibres in both the internal layer of the median eminence and the posterior pituitary. In both regions, MCH- and oxytocin-IR fibres were found in great proximity, although there was no evidence for synaptic interaction between these two populations at the ultrastructural level. The tracer injection revealed that only mediobasal preoptic MCH neurones project to the posterior pituitary, suggesting a neuroendocrine-modulatory role for this population. When taken together, the results obtained in the present study indicate that neuroplasticity events at the mediobasal preoptic hypothalamus that occur during late lactation may be part of a neuroendocrinology control loop involving both MCH and oxytocin.

Assuntos

Hormônios Hipotalâmicos/metabolismo , Eminência Mediana/citologia , Eminência Mediana/metabolismo , Melaninas/metabolismo , Hipófise/citologia , Hipófise/metabolismo , Hormônios Hipofisários/metabolismo , Animais , Feminino , Lactação/metabolismo , Ocitocina/metabolismo , Precursores de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Ratos Long-Evans

RESUMO

Cytoglobin (Cygb) is a hexacoordinate protein, associated with the transport of oxygen, nitric oxide scavenging, tumor suppression and protection against oxidative stress and inflammation. This protein is expressed in brain areas including the preoptic area (POA) of the anterior hypothalamus, the region responsible for the regulation of body temperature. In this study, we show that Cygb is upregulated in the rat hypothalamus 2.5 h and 5 h after intravenous administration of lipopolysaccharide (LPS). We investigated the effect of treatment with Cygb in POA primary cultures stimulated with LPS for 4 h. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured and the results showed that Cygb reduced the concentrations of both cytokines. We further observed a decrease in immunoreactivity of the inflammatory transcription factor nuclear factor-κB (NF-κB), but not NF-IL6 and STAT3, in the nucleus of Cygb-treated POA cells. These findings suggest that Cygb attenuates the secretion of IL-6 and TNF-α in LPS-stimulated POA primary cultures via inhibition of the NF-κB signaling pathway, indicating that this protein might play an important role in the control of neuroinflammation and fever.

RESUMO

Both animal and human studies have provided conclusive evidence that oxytocin (OXT) acts in the brain (eg, medial preoptic area, ventral tegmental area, nucleus accumbens) to promote parental behaviour under different reproductive and physiological conditions. OXT appears to accelerate and strengthen the neural process that makes newborns attractive or rewarding. Furthermore, OXT reduces stress/anxiety and might improve mood and well being, resulting in indirect benefits for parents. However, OXT also plays a role in the development of species reproductive and social strategies, making some species or individuals more prone to display caring activities in nonreproductive contexts. There are important differences in the development of the OXT system and its regulation by gonadal hormones that can make individuals or species very different. Those intra- and interspecific differences in the OXT system have been associated with differences in parental behaviour. For example, differences in OXT levels in body fluids and genetic variants for the OXT and OXT receptor genes have been associated with variability in parental mood and behaviour in humans. Thus, OXT has received much attention as a potential therapeutic agent for affective, emotional and behavioural problems. Despite many preliminary studies indicating promising findings, several unknown aspects of the OXT system remain to be addressed before we can achieve a complete understanding of its function in the brain. The enormous interest that this area of study has attracted in the last decade will likely continually contribute to advancing our understanding of the role of OXT in parental behaviour and other behavioural and physiological functions.

Assuntos

Encéfalo/fisiologia , Comportamento Materno/fisiologia , Ocitocina/fisiologia , Comportamento Paterno/fisiologia , Receptores de Ocitocina/fisiologia , Animais , Emoções/fisiologia , Feminino , Masculino , Recompensa

RESUMO

Clock gene oscillations are necessary for a successful pregnancy and parturition, but little is known about their function during lactation, a period demanding from the mother multiple physiological and behavioral adaptations to fulfill the requirements of the offspring. First, we will focus on circadian rhythms and clock genes in reproductive tissues mainly in rodents. Disruption of circadian rhythms or proper rhythmic oscillations of clock genes provoke reproductive problems, as found in clock gene knockout mice. Then, we will focus mainly on the rabbit doe as this mammal nurses the young just once a day with circadian periodicity. This daily event synchronizes the behavior and the activity of specific brain regions critical for reproductive neuroendocrinology and maternal behavior, like the preoptic area. This region shows strong rhythms of the PER1 protein (product of the Per1 clock gene) associated with circadian nursing. Additionally, neuroendocrine cells related to milk production and ejections are also synchronized to daily nursing. A threshold of suckling is necessary to entrain once a day nursing; this process is independent of milk output as even virgin does (behaving maternally following anosmia) can display circadian nursing behavior. A timing motivational mechanism may regulate such behavior as mesolimbic dopaminergic cells are entrained by daily nursing. Finally, we will explore about the clinical importance of circadian rhythms. Indeed, women in chronic shift-work schedules show problems in their menstrual cycles and pregnancies and also have a high risk of preterm delivery, making this an important field of translational research.