RESUMO
Hypertension is a global health burden. The hypothalamic paraventricular nucleus (PVN) is an essential component of the neuronal network that regulates sodium homeostasis and blood pressure (BP). Previously, we have shown PVN-specific G protein-coupled receptor-coupled Gαi2 subunit proteins are essential to counter the development of salt-sensitive hypertension by mediating the sympathoinhibitory and natriuretic responses to increased dietary sodium intake to maintain sodium homeostasis and normotension. However, the cellular localization and identity of PVN Gαi2-expressing neurons are currently unknown. In this study using in situ hybridization, we determined the neuroanatomical characterization of Gαi2-expressing PVN neurons in 3-mo-old male and female Sprague-Dawley rats. We observed that Gαi2-expressing neurons containing Gnai2 mRNA are highly localized in the parvocellular region of the hypothalamic PVN. At level 2 of the hypothalamic PVN, Gnai2 mRNA colocalized with â¼ 85% of GABA-expressing neurons and â¼28% of glutamatergic neurons. Additionally, within level 2 Gnai2 mRNA colocalized with â¼75% of corticotrophin-releasing hormone PVN neurons. Gnai2 neurons had lower colocalization with tyrosine hydroxylase (â¼33%)-, oxytocin (â¼6%)-, and arginine vasopressin (â¼10%)-expressing parvocellular neurons in level 2 PVN. Colocalization was similar among male and female rats. The high colocalization of Gnai2 mRNA with GABAergic neurons, in conjunction with our previous findings that PVN Gαi2 proteins mediate sympathoinhibition, suggests that Gαi2 proteins potentially modulate GABAergic signaling to impact sympathetic outflow and BP.
Assuntos
Subunidade alfa Gi2 de Proteína de Ligação ao GTP/metabolismo , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/citologia , Animais , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Neurônios GABAérgicos/metabolismo , Ácido Glutâmico/metabolismo , Masculino , Ocitocina/metabolismo , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of Sim1-expressing cell types that comprise a major autonomic output nucleus and play critical roles in the control of food intake and energy homeostasis. The roles of specific PVH neuronal subtypes in energy balance have yet to be defined, however. The PVH contains nitric oxide synthase-1 (Nos1)-expressing (Nos1(PVH)) neurons of unknown function; these represent a subset of the larger population of Sim1-expressing PVH (Sim1(PVH)) neurons. To determine the role of Nos1(PVH) neurons in energy balance, we used Cre-dependent viral vectors to both map their efferent projections and test their functional output in mice. Here we show that Nos1(PVH) neurons project to hindbrain and spinal cord regions important for food intake and energy expenditure control. Moreover, pharmacogenetic activation of Nos1(PVH) neurons suppresses feeding to a similar extent as Sim1(PVH) neurons, and increases energy expenditure and activity. Furthermore, we found that oxytocin-expressing PVH neurons (OXT(PVH)) are a subset of Nos1(PVH) neurons. OXT(PVH) cells project to preganglionic, sympathetic neurons in the thoracic spinal cord and increase energy expenditure upon activation, though not to the same extent as Nos1(PVH) neurons; their activation fails to alter feeding, however. Thus, Nos1(PVH) neurons promote negative energy balance through changes in feeding and energy expenditure, whereas OXT(PVH) neurons regulate energy expenditure alone, suggesting a crucial role for non-OXT Nos1(PVH) neurons in feeding regulation.
Assuntos
Regulação do Apetite/fisiologia , Metabolismo Energético/fisiologia , Neurônios/fisiologia , Óxido Nítrico Sintase Tipo I/fisiologia , Núcleo Hipotalâmico Paraventricular/citologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Animais , Regulação do Apetite/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Temperatura Corporal/fisiologia , Ingestão de Alimentos/fisiologia , Metabolismo Energético/genética , Masculino , Camundongos , Camundongos Transgênicos , Vias Neurais/citologia , Vias Neurais/fisiologia , Técnicas de Rastreamento Neuroanatômico , Óxido Nítrico Sintase Tipo I/genética , Ocitocina/fisiologia , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Proteínas Repressoras/fisiologia , Rombencéfalo/anatomia & histologia , Rombencéfalo/citologia , Rombencéfalo/fisiologia , Medula Espinal/anatomia & histologia , Medula Espinal/citologia , Medula Espinal/fisiologiaRESUMO
BACKGROUND: The role of the endothelial cell (EC) in blood flow regulation within the central nervous system has been little studied. Here, we explored EC participation in morphological changes of the anterior hypothalamic paraventricular nucleus (PVN) microvasculature of female rats at two reproductive stages with different metabolic demand (virginity and lactation). We measured the inner capillary diameter (ICD) of 800 capillaries from either the magnocellular or parvocellular regions. The space occupied by neural (somas, dendrites and axons) and glial, but excluding vascular elements of the neurovascular compartment was also measured in 100-µm2 sample fields of both PVN subdivisions. RESULTS: The PVN of both groups of animals showed ICDs that ranged from 3 to 10 microns. The virgin group presented mostly capillaries with small ICD, whereas the lactating females exhibited a significant increment in the percentage of capillaries with larger ICD. The space occupied by the neural and glial elements of the neurovascular compartment did not show changes with lactation. CONCLUSIONS: Our findings suggest that during lactation the microvasculature of the PVN of female rats undergoes dynamic, transitory changes in blood flow as represented by an increment in the ICD through a self-cytoplasmic volume modification reflected by EC changes. A model of this process is proposed.
Assuntos
Vasos Sanguíneos/anatomia & histologia , Capilares/anatomia & histologia , Lactação/fisiologia , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Análise de Variância , Animais , Vasos Sanguíneos/ultraestrutura , Capilares/ultraestrutura , Feminino , Microscopia Eletrônica de Transmissão , Núcleo Hipotalâmico Paraventricular/irrigação sanguínea , Ratos , Ratos WistarRESUMO
It has been known for many decades that nonmammalian vertebrates detect light by deep brain photoreceptors that lie outside the retina and pineal organ to regulate seasonal cycle of reproduction. However, the identity of these photoreceptors has so far remained unclear. Here we report that Opsin 5 is a deep brain photoreceptive molecule in the quail brain. Expression analysis of members of the opsin superfamily identified as Opsin 5 (OPN5; also known as Gpr136, Neuropsin, PGR12, and TMEM13) mRNA in the paraventricular organ (PVO), an area long believed to be capable of phototransduction. Immunohistochemistry identified Opsin 5 in neurons that contact the cerebrospinal fluid in the PVO, as well as fibers extending to the external zone of the median eminence adjacent to the pars tuberalis of the pituitary gland, which translates photoperiodic information into neuroendocrine responses. Heterologous expression of Opsin 5 in Xenopus oocytes resulted in light-dependent activation of membrane currents, the action spectrum of which showed peak sensitivity (lambda(max)) at approximately 420 nm. We also found that short-wavelength light, i.e., between UV-B and blue light, induced photoperiodic responses in eye-patched, pinealectomized quail. Thus, Opsin 5 appears to be one of the deep brain photoreceptive molecules that regulates seasonal reproduction in birds.
Assuntos
Proteínas Aviárias/fisiologia , Encéfalo/fisiologia , Coturnix/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Opsinas/fisiologia , Células Fotorreceptoras de Vertebrados/fisiologia , Sequência de Aminoácidos , Animais , Proteínas Aviárias/genética , Encéfalo/anatomia & histologia , Coturnix/anatomia & histologia , Coturnix/genética , Feminino , Técnicas In Vitro , Masculino , Eminência Mediana/anatomia & histologia , Eminência Mediana/fisiologia , Modelos Neurológicos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/genética , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Oócitos/metabolismo , Opsinas/genética , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Estimulação Luminosa , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Testículo/crescimento & desenvolvimento , Xenopus laevisRESUMO
The worldwide obesity epidemic is increasing, yet at this time, no long-acting and specific pharmaceutical therapies are available. Peripheral hormonal signals communicate metabolic status to the hypothalamus by activating their corresponding receptors in the arcuate nucleus (ARC). In this brain region, a variety of G protein-coupled receptors (GPCRs) are expressed that are potentially involved in weight regulation, but so far, the detailed function of most hypothalamic GPCRs is only partially understood. An important and underappreciated feature of GPCRs is the capacity for regulation via di- and heterodimerization. Increasing evidence implicates that heterodimerization of GPCRs results in profound functional consequences. Recently, we could demonstrate that interaction of the melanocortin 3 receptor (MC3R) and the growth hormone secretagogue receptor (GHSR)-1a results in a modulation of function in both receptors. Although the physiological role of GPCR-GPCR interaction in the hypothalamus is yet to be elucidated, this concept promises new avenues for investigation and understanding of hypothalamic functions dependent on GPCR signaling. Since GPCRs are important targets for drugs to combat many diseases, identification of heterodimers may be a prerequisite for highly specific drugs. Therefore, a detailed understanding of the mechanisms and their involvement in weight regulation is necessary. Fundamental to this understanding is the interplay of GPCR-GPCR in the hypothalamic nuclei in energy metabolism. In this review, we summarize the current knowledge on melanocortin receptors and GHSR-1a in hypothalamic weight regulation, especially as they pertain to possible drug targets. Furthermore, we include available evidence for the participation and significance of GPCR dimerization.
Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Peso Corporal/fisiologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Receptor Tipo 3 de Melanocortina/metabolismo , Receptor Tipo 4 de Melanocortina/metabolismo , Receptores de Grelina/metabolismo , Animais , Regulação do Apetite/fisiologia , Núcleo Arqueado do Hipotálamo/anatomia & histologia , Núcleo Arqueado do Hipotálamo/fisiologia , Humanos , Modelos Biológicos , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Multimerização Proteica/fisiologia , Receptor Tipo 3 de Melanocortina/fisiologia , Receptor Tipo 4 de Melanocortina/fisiologia , Receptores de Grelina/fisiologiaRESUMO
The paraventricular nucleus of the hypothalamus (PVN) is a cell group that plays important roles in regulating sympathetic vasomotor tone, food intake, neuroendocrine and autonomic stress responses, and cardiovascular function. The developing PVN is surrounded by neuronal elements containing, and presumably secreting, gamma-aminobutyric acid (GABA). The vasculature of the adult PVN is notably denser than in other brain regions or in the PVN during perinatal development. To characterize the postnatal angiogenic process in mice, blood vessels were analyzed at P8, 20, and 50 in rostral, mid, and caudal divisions of the PVN in males and females. Vascular changes relative to disruption of the R1 subunit of the GABA(B) receptor were evaluated at P8 and P20. For defined regions of interest within the PVN there were age dependent increases in blood vessel lengths and branching from P8 to 20 to 50 with the most notable increases in the middle region. Loss of GABA(B) receptors did not influence vascular characteristics at P8 in any region, but by P20 there was significantly (20%) less blood vessel length and branching in the mid-PVN region vs. wild type. These findings suggest that the loss of GABA(B) signaling may lead to a late developing defect in angiogenesis. The loss of vascularity with defective GABA(B) signaling suggests that neurovascular relationships in the PVN may be an important locus for understanding disorders of the hypothalamic-pituitary-adrenal axis with potential impact for psychiatric mood disorders along with other comorbid disorders that may be regulated by cells in the PVN.
Assuntos
Vasos Sanguíneos/crescimento & desenvolvimento , Vasos Sanguíneos/metabolismo , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/irrigação sanguínea , Transdução de Sinais , Ácido gama-Aminobutírico/metabolismo , Animais , Vasos Sanguíneos/anatomia & histologia , Camundongos , Camundongos Endogâmicos C57BL , Núcleo Hipotalâmico Paraventricular/metabolismo , Receptores de GABA-B/metabolismoRESUMO
The neuropeptide arginine vasotocin (AVT: the avian homolog of vasopressin) has numerous functional roles including mediating social behaviors, coregulating the adrenocortical stress response and maintaining water balance. These functions of AVT make it susceptible to environmental influence, yet little is understood concerning the variation in the AVT system across habitats. In this study, AVT immunoreactivity was compared between male curve-billed thrashers, Toxostoma curvirostre, from native Sonoran Desert locations and those within the city of Phoenix, Ariz. Previous research found that urban thrashers are more responsive to territorial intrusion, secrete more corticosterone (CORT) during capture stress, and they may also have greater access to water than desert counterparts. Variation in AVT immunoreactivity was also related to levels of plasma CORT and osmolality, and with behavioral responses to a simulated territorial intrusion. Birds from these two habitats showed different AVT immunoreactive patterns in two brain regions: the paraventricular nucleus of the hypothalamus and the medial bed nucleus of the stria terminalis (BSTM), a part of the limbic system. Immunoreactive AVT within the paraventricular nucleus was associated with plasma CORT levels in urban, but not desert, birds, but no such association with osmolality was observed in birds from either habitat. The total number of BSTM AVT-immunoreactive cells was related to a decreased responsiveness to territorial intrusion. These data suggest that divergence in the AVT system between urban and desert thrashers may help explain observed differences in both the adrenocortical stress response and territorial behavior between populations. Whether differences in water availability between habitats contribute to population differences in the brain AVT system is unknown.
Assuntos
Encéfalo/imunologia , Passeriformes/imunologia , Estresse Fisiológico/imunologia , Territorialidade , Vasotocina/imunologia , Animais , Encéfalo/anatomia & histologia , Corticosterona/sangue , Comportamento de Retorno ao Território Vital/fisiologia , Masculino , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/imunologia , Passeriformes/classificação , Passeriformes/fisiologia , Núcleos Septais/anatomia & histologia , Núcleos Septais/imunologia , Estresse Fisiológico/fisiologiaRESUMO
Increasing body core temperature reflexly decreases renal blood flow (RBF), and the hypothalamic paraventricular nucleus (PVN) plays an essential role in this response. ANG II in the brain is involved in the cardiovascular responses to hyperthermia, and ANG II receptors are highly concentrated in the PVN. The present study investigated whether ANG II in the PVN contributes to the cardiovascular responses elicited by hyperthermia. Rats anesthetized with urethane (1-1.4 g/kg iv) were microinjected bilaterally into the PVN (100 nl/side) with saline (n = 5) or losartan (1 nmol/100 nl) (n = 7), an AT1 receptor antagonist. Body core temperature was then elevated from 37°C to 41°C and blood pressure (BP), heart rate (HR), RBF, and renal vascular conductance (RVC) were monitored. In separate groups losartan (n = 4) or saline (n = 4) was microinjected into the PVN, but body core temperature was not elevated. Increasing body core temperature in control rats elicited significant decreases in RBF (-48 ± 5% from a resting level of 14.3 ± 1.4 ml/min) and MVC (-40 ± 4% from a resting level of 0.128 ± 0.013 ml/min·mmHg), and these effects were entirely prevented by pretreatment with losartan. In rats in which body core temperature was not altered, losartan microinjected into the PVN had no significant effects on these variables. The results suggest that endogenous ANG II acts on AT1 receptors in the PVN to mediate the reduction in RBF induced by hyperthermia.
Assuntos
Febre/fisiopatologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Receptor Tipo 1 de Angiotensina/fisiologia , Reflexo/fisiologia , Circulação Renal/fisiologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Losartan/farmacologia , Masculino , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Circulação Renal/efeitos dos fármacos , Cloreto de Sódio/farmacologiaRESUMO
We previously reported that in a eusocial rodent, the naked mole-rat (Heterocephalus glaber), traditional neural sex differences were absent; instead, neural dimorphisms were associated with breeding status. Here we examined the same neural regions previously studied in naked mole-rats in a second eusocial species, the Damaraland mole-rat (Fukomys damarensis). Damaraland mole-rats live in social groups with breeding restricted to a small number of animals. However, colony sizes are much smaller in Damaraland mole-rats than in naked mole-rats and there is consequently less reproductive skew. In this sense, Damaraland mole-rats may be considered intermediate in social organization between naked mole-rats and more traditional laboratory rodents. We report that, as in naked mole-rats, breeding Damaraland mole-rats have larger volumes of the principal nucleus of the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus than do subordinates, with no effect of sex on these measures. Thus, these structures may play special roles in breeders of eusocial species. However, in contrast to what was seen in naked mole-rats, we also found sex differences in Damaraland mole-rats: volume of the medial amygdala and motoneuron number in Onuf's nucleus were both greater in males than in females, with no significant effect of breeding status. Thus, both sex and breeding status influence neural morphology in Damaraland mole-rats. These findings are in accord with the observed sex differences in body weight and genitalia in Damaraland but not naked mole-rats. We hypothesize that the increased sexual dimorphism in Damaraland mole-rats relative to naked mole-rats is related to reduced reproductive skew.
Assuntos
Sistema Nervoso Central/anatomia & histologia , Sistema Nervoso Central/fisiologia , Dominação-Subordinação , Ratos-Toupeira/fisiologia , Tonsila do Cerebelo/anatomia & histologia , Tonsila do Cerebelo/fisiologia , Análise de Variância , Animais , Peso Corporal/fisiologia , Contagem de Células , Tamanho Celular , Feminino , Masculino , Neurônios Motores/fisiologia , Neurônios/fisiologia , Neurônios/ultraestrutura , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Núcleos Septais/anatomia & histologia , Núcleos Septais/fisiologia , Caracteres Sexuais , Comportamento Sexual Animal/fisiologia , Medula Espinal/anatomia & histologia , Medula Espinal/fisiologiaRESUMO
The transneuronal tracer pseudorabies virus was used to test the hypothesis that connections from the cervix to the forebrain and hypothalamus are maintained with pregnancy. The virus was injected into the cervix of nonpregnant or pregnant mice, and, after 5 days, virus-labeled cells and fibers were found in specific forebrain regions and, most prominently, in portions of the hypothalamic paraventricular nucleus. With pregnancy, fewer neurons and fibers were evident in most brain regions compared to that in nonpregnant mice. In particular, little or no virus was found in the medial and ventral parvocellular subdivisions, anteroventral periventricular nucleus, or motor cortex in pregnant mice. By contrast, labeling of virus was sustained in the dorsal hypothalamus and suprachiasmatic nucleus in all groups. Based upon image analysis of digitized photomicrographs, the area with label in the rostral and medial parvocellular paraventricular nucleus and magnocellular subdivisions was significantly reduced in mice whose cervix was injected with virus during pregnancy than in nonpregnant mice. The findings indicate that connections from the cervix to brain regions that are involved in sensory input and integrative autonomic functions are reduced during pregnancy. The findings raise the possibility that remaining pathways from the cervix to the forebrain and hypothalamus may be important for control of pituitary neuroendocrine secretion, as well as for effector functions in the cervix as pregnancy nears term.
Assuntos
Colo do Útero/inervação , Vias Neurais/crescimento & desenvolvimento , Vias Neurais/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Prenhez/fisiologia , Prosencéfalo/fisiologia , Animais , Colo do Útero/anatomia & histologia , Feminino , Herpesvirus Suídeo 1 , Processamento de Imagem Assistida por Computador , Camundongos , Camundongos Endogâmicos C3H , Vias Neurais/anatomia & histologia , Sistemas Neurossecretores/fisiologia , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Gravidez , Prosencéfalo/anatomia & histologia , Núcleo Supraquiasmático/citologia , Núcleo Supraquiasmático/fisiologiaRESUMO
Testosterone is well known to regulate sexual behavior in males, but this is dependent upon prior sexual experience. Aging is associated with decreased libido and changes in testosterone, but the role of experience in these age-related processes has not been systematically studied. We examined effects of age and sexual experience on serum hormones (total testosterone, free testosterone, estradiol, LH) and on numbers of androgen receptor (AR) and estrogen receptor alpha (ERalpha) immunoreactive cells in the hypothalamus. Extensive sexual experience was given to male rats at 4 months of age. Rats were euthanized at either 4 months (young) or 12 months (middle-aged (MA)). Comparable sexually naïve male rats were handled and placed into the testing arena but did not receive any sexual experience. Thus, we had four groups: young-naïve, young-experienced, MA-naïve and MA-experienced. Serum hormone levels were assayed, and numbers of AR and ERalpha cells were quantified stereologically in the medial preoptic nucleus (MPN) and the anteroventral periventricular nucleus (AVPV). Sexually experienced males had significantly elevated serum testosterone and free testosterone in both age groups. Both total and free testosterone were higher, and estradiol lower, in middle-aged than young rats. Experience did not alter either AR or ERalpha expression in the preoptic brain regions studied. Aging was associated with increased expression of AR, but no change in ERalpha. These results show that sexual experience can induce short-term and long-term alterations in serum hormones but these effects are not manifested upon their receptors in the hypothalamus.
Assuntos
Envelhecimento/fisiologia , Hormônios Esteroides Gonadais/sangue , Hipotálamo/fisiologia , Receptores de Esteroides/metabolismo , Comportamento Sexual Animal/fisiologia , Animais , Contagem de Células , Estradiol/sangue , Receptor alfa de Estrogênio/metabolismo , Hipotálamo/anatomia & histologia , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Área Pré-Óptica/anatomia & histologia , Área Pré-Óptica/fisiologia , Distribuição Aleatória , Ratos , Receptores Androgênicos/metabolismo , Testosterona/sangueRESUMO
The paraventricular nucleus (PVN) and the periventricular nucleus (Pe) are important neuroendocrine centers, but the neuronal input to these regions is poorly defined in nonrodent species. We utilized the retrograde transport of injected tracers to determine the neural input to these two nuclei in the ovine brain. Adult Corriedale ewes were studied following FluoroGold injection into either the PVN (n = 5) or the Pe (n = 3). Both the PVN and the Pe were found to receive neuronal input from a number of hypothalamic nuclei. Projections to the PVN from the lateral hypothalamic area were from neurons that produce melanin-concentrating hormone or orexins and a subset of those from the arcuate nucleus were immunopositive for neuropeptide Y and gamma-melanocyte stimulating hormone. This pathway was verified by staining of terminals in the PVN. Input to the PVN from the brain stem was seen to originate from the catecholaminergic and serotoninergic neurons. The projections to the PVN and Pe from hypothalamic and brain stem regions in the sheep brain are generally similar to those in the rat, with some minor differences. These studies highlight the differences in the afferent input to these two closely related nuclei in the ovine brain.
Assuntos
Hipotálamo/anatomia & histologia , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Ovinos/anatomia & histologia , Animais , Núcleo Arqueado do Hipotálamo/anatomia & histologia , Núcleo Arqueado do Hipotálamo/metabolismo , Catecolaminas/metabolismo , Feminino , Corantes Fluorescentes , Hormônios Hipotalâmicos/metabolismo , Hipotálamo/metabolismo , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Melaninas/metabolismo , Vias Neurais/anatomia & histologia , Vias Neurais/metabolismo , Neurônios Aferentes/metabolismo , Neuropeptídeo Y/metabolismo , Neuropeptídeos/metabolismo , Orexinas , Núcleo Hipotalâmico Paraventricular/metabolismo , Hormônios Hipofisários/metabolismo , Serotonina/metabolismo , gama-MSH/metabolismoRESUMO
Early adverse experiences often have devastating consequences. However, whether preweaning paternal deprivation (PD) affects emotional and social behaviors and their underlying neural mechanisms remain unexplored. Using monogamous mandarin voles, we found that PD increased anxiety-like behavior and attenuated social preference in adulthood. PD also decreased the number of oxytocin (OT)-positive neurons projecting from the paraventricular nucleus (PVN) and reduced the levels of the medial prefrontal cortex OT receptor protein in females and of the OT receptor and V1a receptor proteins in males. Intra-prelimbic cortical OT injections reversed the PD-induced changes in anxiety-like behavior and social preferences. Optogenetic activation of the prelimbic cortex OT terminals from PVN OT neurons reversed the PD-induced changes in emotion and social preference behaviors, whereas optogenetic inhibition was anxiogenic and impaired social preference in naive voles. These ï¬ndings demonstrate that PD increases anxiety-like behavior and attenuates social preferences through the involvement of PVN OT neuron projections to the prelimbic cortex.
Assuntos
Ansiedade , Vias Neurais/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Privação Paterna , Comportamento Social , Animais , Arvicolinae , Feminino , Masculino , Neurônios/química , Receptores de Ocitocina/análise , Receptores de Vasopressinas/análiseRESUMO
Previously, we demonstrated that stimulation of the paraventricular hypothalamic nucleus diminishes the nociceptive dorsal horn neuronal responses, and this decrease was mediated by oxytocin in the rat. In addition, we have proposed that oxytocin indirectly inhibits sensory transmission in dorsal horn neurons by exciting spinal inhibitory GABAergic interneurons. The main purpose of the present study was to identify which of the neurons projecting to supraspinal structures to transmit somatic information are modulated by the hypothalamic-spinal descending activation. In anaesthetized rats, single-unit extracellular and juxtacellular recordings were made from dorsal horn lumbar segments, which receive afferent input from the toe and hind-paw regions. The projecting spinothalamic tract and postsynaptic dorsal column system were identified antidromically. Additionally, in order to label the projecting dorsal horn neurons, we injected fluorescent retrograde neuronal tracers into the ipsilateral gracilis nucleus and contralateral ventroposterolateral thalamic nucleus. Hence, juxtacellular recordings were made to iontophoretically label the recorded neurons with a fluorescent dye and identify the recorded projecting cells. We found that only nociceptive evoked responses in spinothalamic tract and postsynaptic dorsal column neurons were significantly inhibited (48.1 +/- 4.6 and 47.7 +/- 8.2%, respectively) and non-nociceptive responses were not affected by paraventricular hypothalamic nucleus stimulation. We conclude that the hypothalamic-spinal system selectively affects the transmission of nociceptive information of projecting spinal cord cells.
Assuntos
Nociceptores/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Células do Corno Posterior/fisiologia , Medula Espinal/citologia , Tratos Espinotalâmicos/citologia , Potenciais de Ação/fisiologia , Animais , Estimulação Elétrica , Eletrofisiologia , Vias Neurais/citologia , Vias Neurais/fisiologia , Nociceptores/citologia , Ocitocina/metabolismo , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Células do Corno Posterior/citologia , Ratos , Ratos WistarRESUMO
Nursing in the rabbit is a circadian event during which mother and pups interact for a period of < 5 min every day. Here we explored behavioral and neuronal changes in the mother by analyzing the suprachiasmatic nucleus (SCN), and oxytocinergic (OT) neurons in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). We maintained lactating does in a light-dark cycle (lights on at 07 : 00 hours; ZT0); they were scheduled to nurse during either the day (ZT03) or the night (ZT19). Groups of intact and nursing females was perfused, one at each 4-h point through a 24-h cycle. We explored, by immunohistochemistry, the PER1 expression and double-labeling, with OT antibody, of neurons in the PVN and SON at lactation on day 7. In the SCN, intact and lactating groups had peak PER1 expression at ZT11; however, there was a reduction in PER1 at peak time in the nursing groups. There was a locomotor activity rhythm with increased activity around the time of lights-on in intact subjects and around the time of suckling in lactating does. There was an induction of PER1 in OT cells in the PVN and SON that shifted in phase with timing of nursing. We further explored the maintenance of the PER1 expression in OT cells in nursing-deprived does and found a significant decrease at 24 and 48 h after the last nursing. We conclude that suckling induced PER1 in the PVN and SON, but not in the SCN, in nursing does, and also shifted their locomotor behavior.
Assuntos
Ritmo Circadiano/genética , Proteínas do Olho/metabolismo , Hipotálamo/metabolismo , Lactação/metabolismo , Atividade Motora/genética , Animais , Proteínas do Olho/genética , Feminino , Expressão Gênica , Hipotálamo/anatomia & histologia , Hipotálamo Anterior/anatomia & histologia , Hipotálamo Anterior/metabolismo , Imuno-Histoquímica , Lactação/genética , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Proteínas Circadianas Period , Estimulação Luminosa , Coelhos , Núcleo Supraquiasmático/anatomia & histologia , Núcleo Supraquiasmático/metabolismo , Fatores de Tempo , Regulação para Cima/fisiologiaRESUMO
Cocaine- and amphetamine-regulated transcript (CART) peptide is widely expressed in the hypothalamus and is involved in the central regulation of energy balance. Using in situ hybridization, this study examined the roles of CART peptide in the hypothalamus of diet-induced obese (DIO) or diet-resistant (DR) mice under different dietary interventions including high-fat (HF), low-fat (LF) and pair-feeding (PF) diet for 6 weeks. Pair feeding the energy intake of the DIO and DR mice was used to determine whether there is an inherent difference in baseline CART expression that may cause the DIO and DR phenotypes. The results demonstrated that CART mRNA expression in the hypothalamus of the DIO mice responded differently on the high-fat diet compared to DR mice. The arcuate nucleus and paraventricular nucleus showed a significant reduction in CART mRNA expression in DIO mice compared to DR mice on the HF diet (-19.6%, p=0.019; -26.1%, p=0.003); whilst a profound increase in CART mRNA expression was observed in the dorsomedial nucleus and lateral hypothalamic area (+44.5%, p=0.007; +37.4%, p=0.033). Our study suggests that the decrease of CART mRNA expression in Arc and PVN regions of DIO mice may contribute to the development of high-fat diet-induced obesity. In addition, CART in the dorsomedial nucleus (DM) of hypothalamus and lateral hypothalamus (LH) may be involved in the activation of an orexigenic effect. Since pair feeding of the high-fat diet eliminated both the body weight and CART mRNA differences between the DIO and DR mice, it is likely that their alterations in gene expression were a consequence of their dissimilar body weight levels.
Assuntos
Peso Corporal/fisiologia , Hipotálamo/metabolismo , Proteínas do Tecido Nervoso/genética , Obesidade/dietoterapia , Obesidade/metabolismo , RNA Mensageiro/metabolismo , Tecido Adiposo/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/anatomia & histologia , Núcleo Arqueado do Hipotálamo/metabolismo , Restrição Calórica , Núcleo Hipotalâmico Dorsomedial/anatomia & histologia , Núcleo Hipotalâmico Dorsomedial/metabolismo , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Alimentos Formulados , Regulação da Expressão Gênica/fisiologia , Região Hipotalâmica Lateral/anatomia & histologia , Região Hipotalâmica Lateral/metabolismo , Hipotálamo/anatomia & histologia , Leptina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Núcleo Hipotalâmico Paraventricular/metabolismoRESUMO
It is morphologically demonstrated that the subfornical organ (SFO) projects to the paraventricular hypothalamic nucleus (PVN) and also projects to the nucleus preopticus medianus (POMe), a relay nucleus of indirect projections from the SFO to PVN. However, it remains unknown, whether or not SFO neurons project collaterally to the POMe and PVN. To confirm this, a double retrograde labeling method was performed on rats using two fluorescent tracers. One tracer (red-colored FluoSpheres: FSR) was injected into the POMe and the other (Fast Blue: FB) was injected into the unilateral PVN at the same time. As a result, many retrogradely labeled neurons were found in the entire SFO. Of these, some neurons showed both FSR and FB fluorescence. Double-labeled neurons were found in about 8.7% of FSR-labeled neurons and 15.5% of FB-labeled neurons. The existence of double-labeled neurons indicates that single neurons in the SFO project simultaneously to the POMe and PVN via collateral axon branches. The data suggest that there are complicated neuronal pathways originating from the SFO in regulating cardiovascular and body fluid homeostasis.
Assuntos
Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Área Pré-Óptica/anatomia & histologia , Órgão Subfornical/anatomia & histologia , Animais , Axônios/fisiologia , Axônios/ultraestrutura , Mapeamento Encefálico , Fenômenos Fisiológicos Cardiovasculares , Corantes Fluorescentes , Homeostase/fisiologia , Masculino , Microesferas , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
As a starting point for constructing a high-resolution, resliceable computer graphics model for the extraction, quantitative analysis, display, and modeling of neuroanatomical data the outer border and the boundaries of inner divisions and parts of the paraventricular nucleus have been drawn for all 39 serial histological sections prepared for a published reference atlas of the rat brain. This careful parceling revealed three new features of paraventricular nucleus topography: the full rostral extent of the anterior parvicellular part, the caudal end of the medial magnocellular part, and a thin rostrolateral extension of the dorsal medial parvicellular part composed at least in part of neurons expressing corticotropin-releasing hormone. The vector graphics drawings were aligned using the already established alignment of nine consecutive, relevant Atlas Levels, and then contours were smoothed to eliminate nonlinear distortions associated with histological mounting. This dataset was then used to create three-dimensional contour and surface models of the paraventricular nucleus, as well as two-dimensional horizontal and sagittal projections of its outer border. The computer graphics files containing raw and smoothed drawings for all 39 serial sections are supplied for use by researchers interested in developing new or better computer graphics analysis tools involving the paraventricular nucleus. This work may also stimulate the long range goal of creating a high-resolution, resliceable, computer graphics model of the whole brain, and eventually the whole nervous system, that is useful for quantitative analysis and topological transformation.
Assuntos
Atlas como Assunto , Mapeamento Encefálico/métodos , Simulação por Computador , Processamento de Imagem Assistida por Computador/métodos , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Animais , Arginina Vasopressina/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Diencéfalo/anatomia & histologia , Masculino , Microtomia , Sistemas Neurossecretores/anatomia & histologia , Sistemas Neurossecretores/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Ratos , Ratos Sprague-Dawley , Software , Especificidade da EspécieRESUMO
OBJECTIVE: To investigate the effects of androgen on sexually dimorphism nucleus in preoptic area (SDN-POA) and anteroventral periventricular nucleus (AVPV) before sexual differentiation of the brain in female rats. METHODS: Neonatal female SD rats (n=12) were randomly divided into two groups: androgen group and control group. Twenty-four hours after birth animals were subjected to intraperitoneal injection of 50 microl of testosterone propionate (TP,10.0 g/L) or aseptic oil as control. The rats were sacrificed 60 days after the injection and the brains were collected for crystal violet staining. LEICA Q Win system was applied in detecting the boundaries of SDN-POA and AVPV, then the volumes of SDN-POA and AVPV were calculated. RESULTS: The volumes of SDN-POA in androgen group were significantly larger than those in control group [(16.77+/-2.68) vs (8.99+/-1.42)mm(3)x10(-3), P<0.01], while the volumes of AVPV in androgen group were significantly smaller than those in control group [(9.14+/-1.16) vs (14.62+/-2.80)mm(3)x10(-3), P<0.01]. CONCLUSION: Exogenous androgen rendered before sexual differentiation in female rats results in enlargement of SDN-POA volumes and reduction of AVPV.
Assuntos
Androgênios/farmacologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Área Pré-Óptica/efeitos dos fármacos , Diferenciação Sexual , Animais , Animais Recém-Nascidos , Feminino , Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Área Pré-Óptica/anatomia & histologia , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
In the present study a histochemical investigation of the SO and PV nuclei of the hypothalamic-pituitary neurosecretory system are presented at different periods of the water deprivation. The experiments were carried out on laboratory rats (n = 50), weighing 200-250 grams. The experimental and control animals days was maintained at different feeding ration. The control rats (I) were given food and water, the experimental animals (II, III, IV, V) for five days were given the dry food only. Following the 5-day water deprivation, the animals of the Groups III, IV, and V, had given free access to water for 15, 30, and 45 days. In order to investigate histological properties, the animals were rapidly beheaded. In order to reveal a neurosecrete, the 5-10 mm thick slices of the hypothalamus and pituitary gland were stained with the Nissle method. Evaluation of the morphological-functional state of the HPNSS a working scheme of the neurosecretory cycle has been utilized. Analysis of the above data allows concluding that following prolonged water deprivation, recovery level of the structural-metabolic components in the hypothalamic SO and PV nuclei is not uniform. Deeper morphological changes occur in the large-granular region than in the small-granular one, where no significant changes are found; respectively, these cells recover much earlier. Capacity for restoration of the structural-metabolic complex varies and depends on functional properties of the cellular content of these nuclei.