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Sample records for arcuate nucleus neuropeptide

  1. Preferential development of neuropeptide Y/GABA circuit in hypothalamic arcuate nucleus in postnatal rats.

    PubMed

    Sun, Xiaoping; Fukami, Tatsuya; Li, Tie; Desai, Mina; Ross, Michael G

    2016-03-15

    The hypothalamus, which plays a critical role in regulation of energy homeostasis, is formed during the perinatal period and thus vulnerable to fetal/newborn environmental conditions. We investigated synaptogenesis and neurotransmission of neurons in arcuate nucleus of the hypothalamus (ARH) during the postnatal period using immunohistochemical and electrophysiological methods. Our results show that the density of neuropeptide Y (NPY) fibers increases abruptly after the second postnatal week. NPY and proopiomelanocortin (POMC) immunoreactive fibers/varicosities puncta are mutually juxtaposed to perikarya of both neurons with increasing NPY and decreasing POMC apposition until the third postnatal week. The frequencies of spontaneous GABAergic inhibitory and glutamatergic excitatory postsynaptic currents (sIPSC and sEPSC) increase with age, with action potential dependent sIPSCs predominant during first postnatal week and sEPSCs thereafter. The presynaptic function of ARH synapses appears to reach adult levels around the age of weaning, while the postsynaptic receptors are still undergoing modification, evidenced by changes of frequencies, amplitudes and deactivation kinetics of PSCs. The number of NPY fibers juxtaposed to NPY neurons is correlated with the frequency of postsynaptic currents, suggesting that NPY/GABA release may facilitate maturation of synapses on their innervated neurons. Our results indicate that a neural circuit in ARH with a stronger NPY/GABAergic tone undergoes significant development during the postnatal period, which may be important for the maturation and/or remodeling of ARH neural circuits. PMID:26790345

  2. Moderate long-term modulation of neuropeptide Y in hypothalamic arcuate nucleus induces energy balance alterations in adult rats.

    PubMed

    Sousa-Ferreira, Lígia; Garrido, Manuel; Nascimento-Ferreira, Isabel; Nobrega, Clévio; Santos-Carvalho, Ana; Alvaro, Ana Rita; Rosmaninho-Salgado, Joana; Kaster, Manuella; Kügler, Sebastian; de Almeida, Luís Pereira; Cavadas, Claudia

    2011-01-01

    Neuropeptide Y (NPY) produced by arcuate nucleus (ARC) neurons has a strong orexigenic effect on target neurons. Hypothalamic NPY levels undergo wide-ranging oscillations during the circadian cycle and in response to fasting and peripheral hormones (from 0.25 to 10-fold change). The aim of the present study was to evaluate the impact of a moderate long-term modulation of NPY within the ARC neurons on food consumption, body weight gain and hypothalamic neuropeptides. We achieved a physiological overexpression (3.6-fold increase) and down-regulation (0.5-fold decrease) of NPY in the rat ARC by injection of AAV vectors expressing NPY and synthetic microRNA that target the NPY, respectively. Our work shows that a moderate overexpression of NPY was sufficient to induce diurnal over-feeding, sustained body weight gain and severe obesity in adult rats. Additionally, the circulating levels of leptin were elevated but the immunoreactivity (ir) of ARC neuropeptides was not in accordance (POMC-ir was unchanged and AGRP-ir increased), suggesting a disruption in the ability of ARC neurons to response to peripheral metabolic alterations. Furthermore, a dysfunction in adipocytes phenotype was observed in these obese rats. In addition, moderate down-regulation of NPY did not affect basal feeding or normal body weight gain but the response to food deprivation was compromised since fasting-induced hyperphagia was inhibited and fasting-induced decrease in locomotor activity was absent.These results highlight the importance of the physiological ARC NPY levels oscillations on feeding regulation, fasting response and body weight preservation, and are important for the design of therapeutic interventions for obesity that include the NPY. PMID:21799827

  3. Neuromedin B and gastrin releasing peptide excite arcuate nucleus neuropeptide Y neurons in a novel transgenic mouse expressing strong renilla GFP in NPY neurons

    PubMed Central

    van den Pol, Anthony N.; Yao, Yang; Fu, Li-Ying; Foo, Kylie; Huang, Hao; Coppari, Roberto; Lowell, Brad; Broberger, Christian

    2009-01-01

    Neuropeptide Y (NPY) is one of the most widespread neuropeptides in the brain. Transgenic mice were generated that expressed bright renilla GFP in most or all of the known NPY cells in the brain, which otherwise were not identifiable. GFP expression in NPY cells was confirmed with immunocytochemistry and single cell RT-PCR. NPY neurons in the hypothalamic arcuate nucleus play an important role in energy homeostasis and endocrine control. Whole cell patch clamp recording was used to study identified arcuate NPY cells. Primary agents that regulate energy balance include melanocortin receptor agonists, AgRP, and cannabinoids; none of these substances substantially influenced electrical properties of NPY neurons. In striking contrast, neuropeptides of the bombesin family, including gastrin releasing peptide and neuromedin B which are found in axons in the arcuate nucleus and may also be released from the gut to signal the brain, showed strong direct excitatory actions at nanomolar levels on the NPY neurons, stronger than the actions of ghrelin and hypocretin/orexin. Bombesin-related peptides reduced input resistance and depolarized the membrane potential. The depolarization was attenuated by several factors: substitution of choline for sodium, extracellular Ni2+, inclusion of BAPTA in the pipette, KB-R7943 and SKF96365. Reduced extracellular calcium enhanced the current, which reversed around − 20 mV. Together, these data suggest two mechanisms, activation of non-selective cation channels and the sodium/calcium exchanger. Since both NPY and POMC neurons, which we also studied, are similarly directly excited by bombesin-like peptides, the peptides may function to initiate broad activation, rather than the cell-type selective activation or inhibition reported for many other compounds that modulate energy homeostasis. PMID:19357287

  4. Developmental Changes in Synaptic Distribution in Arcuate Nucleus Neurons

    PubMed Central

    Kirigiti, Melissa A.; Baquero, Karalee C.; Lee, Shin J.; Smith, M. Susan; Grove, Kevin L.

    2015-01-01

    Neurons coexpressing neuropeptide Y, agouti-related peptide, and GABA (NAG) play an important role in ingestive behavior and are located in the arcuate nucleus of the hypothalamus. NAG neurons receive both GABAergic and glutamatergic synaptic inputs, however, the developmental time course of synaptic input organization of NAG neurons in mice is unknown. In this study, we show that these neurons have low numbers of GABAergic synapses and that GABA is inhibitory to NAG neurons during early postnatal period. In contrast, glutamatergic inputs onto NAG neurons are relatively abundant by P13 and are comparatively similar to the levels observed in the adult. As mice reach adulthood (9–10 weeks), GABAergic tone onto NAG neurons increases. At this age, NAG neurons received similar numbers of inhibitory and EPSCs. To further differentiate age-associated changes in synaptic distribution, 17- to 18-week-old lean and diet-induced obesity (DIO) mice were studied. Surprisingly, NAG neurons from lean adult mice exhibit a reduction in the GABAergic synapses compared with younger adults. Conversely, DIO mice display reductions in the number of GABAergic and glutamatergic inputs onto NAG neurons. Based on these experiments, we propose that synaptic distribution in NAG neurons is continuously restructuring throughout development to accommodate the animals' energy requirements. PMID:26041922

  5. Role of the hypothalamic arcuate nucleus in cardiovascular regulation

    PubMed Central

    Sapru, Hreday N.

    2012-01-01

    Recently the hypothalamic arcuate nucleus (Arc) has been implicated in cardiovascular regulation. Both pressor and depressor responses can be elicited by the chemical stimulation of the Arc. The direction of cardiovascular responses (increase or decrease) elicited from the Arc depends on the baseline blood pressure. The pressor responses are mediated via increase in sympathetic nerve activity and involve activation of the spinal ionotropic glutamate receptors. Arc-stimulation elicits tachycardic responses which are mediated via inhibition of vagal input and excitation of sympathetic input to the heart. The pathways within the brain mediating the pressor and tachycardic responses elicited from the Arc have not been delineated. The depressor responses to the Arc-stimulation are mediated via the hypothalamic paraventricular nucleus (PVN). Gamma aminobutyric acid type A receptors, neuropeptide Y1 receptors, and opiate receptors in the PVN mediate the depressor responses elicited from the Arc. Some circulating hormones (e.g., leptin and insulin) may reach the Arc via the leaky blood-brain barrier and elicit their cardiovascular effects. Although the Arc is involved in mediating the cardiovascular responses to intravenously injected angiotensin II and angiotensin-(1-12), these effects may not be due to leakage of these peptides across the blood-brain barrier in the Arc; instead, circulating angiotensins may act on neurons in the SFO and mediate cardiovascular actions via the projections of SFO neurons to the Arc. Cardiovascular responses elicited by acupuncture have been reported to be mediated by direct and indirect projections of the Arc to the RVLM. PMID:23260431

  6. Role of the hypothalamic arcuate nucleus in cardiovascular regulation.

    PubMed

    Sapru, Hreday N

    2013-04-01

    Recently the hypothalamic arcuate nucleus (Arc) has been implicated in cardiovascular regulation. Both pressor and depressor responses can be elicited by the chemical stimulation of the Arc. The direction of cardiovascular responses (increase or decrease) elicited from the Arc depends on the baseline blood pressure. The pressor responses are mediated via increase in sympathetic nerve activity and involve activation of the spinal ionotropic glutamate receptors. Arc-stimulation elicits tachycardic responses which are mediated via inhibition of vagal input and excitation of sympathetic input to the heart. The pathways within the brain mediating the pressor and tachycardic responses elicited from the Arc have not been delineated. The depressor responses to the Arc-stimulation are mediated via the hypothalamic paraventricular nucleus (PVN). Gamma aminobutyric acid type A receptors, neuropeptide Y1 receptors, and opiate receptors in the PVN mediate the depressor responses elicited from the Arc. Some circulating hormones (e.g., leptin and insulin) may reach the Arc via the leaky blood-brain barrier and elicit their cardiovascular effects. Although the Arc is involved in mediating the cardiovascular responses to intravenously injected angiotensin II and angiotensin-(1-12), these effects may not be due to leakage of these peptides across the blood-brain barrier in the Arc; instead, circulating angiotensins may act on neurons in the SFO and mediate cardiovascular actions via the projections of SFO neurons to the Arc. Cardiovascular responses elicited by acupuncture have been reported to be mediated by direct and indirect projections of the Arc to the RVLM. PMID:23260431

  7. Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats: Roles of Neuropeptide Y and α-Melanocyte-Stimulating Hormone.

    PubMed

    Shi, Zhigang; Cassaglia, Priscila A; Gotthardt, Laura C; Brooks, Virginia L

    2015-12-01

    Pregnancy increases sympathetic nerve activity (SNA), but the mechanisms are unknown. Here, we investigated the contributions of the hypothalamic paraventricular and arcuate nuclei in α-chloralose-anesthetized pregnant and nonpregnant rats. Baseline arterial pressure (AP) was lower, and heart rate (HR), lumbar sympathetic activity, and splanchnic SNA were higher in pregnant rats compared with nonpregnant rats. Inhibition of the paraventricular nucleus via bilateral muscimol nanoinjections decreased AP and HR more in pregnant rats than in nonpregnant rats and decreased lumbar SNA only in pregnant rats. Similarly, after arcuate muscimol nanoninjections, the decreases in AP, HR, and lumbar, renal, and splanchnic sympathetic nerve activities were greater in pregnant rats than in nonpregnant rats. Major arcuate neuronal groups that project to the paraventricular nucleus express inhibitory neuropeptide Y (NPY) and excitatory α-melanocyte-stimulating hormone. Inhibition of paraventricular melanocortin 3/4 receptors with SHU9119 also decreased AP, HR, and lumbar SNA in pregnant rats but not in nonpregnant rats. Conversely, paraventricular nucleus NPY expression was reduced in pregnant animals, and although blockade of paraventricular NPY Y1 receptors increased AP, HR, and lumbar sympathetic activity in nonpregnant rats, it had no effects in pregnant rats. Yet, the sympathoinhibitory, depressor, and bradycardic effects of paraventricular NPY nanoinjections were similar between groups. In conclusion, the paraventricular and arcuate nuclei contribute to increased basal SNA during pregnancy, likely due in part to decreased tonic NPY inhibition and increased tonic α-melanocyte-stimulating hormone excitation of presympathetic neurons in the paraventricular nucleus. PMID:26483343

  8. Undernutrition during early life alters neuropeptide Y distribution along the arcuate/paraventricular pathway.

    PubMed

    Rocha, M L M; Fernandes, P P; Lotufo, B M; Manhães, A C; Barradas, P C; Tenorio, F

    2014-01-01

    Perinatal nutrient restriction exerts profound influences on brain development. Animals that suffer undernutrition during lactation also display impaired weight gain. Feeding behavior is mainly modulated by neural and hormonal inputs to the hypothalamus. The arcuate-paraventricular neuropeptidergic Y pathway has a prominent role in appetite regulation. The aim of this work was to study the effects of protein undernutrition during lactation on this hypothalamic pathway. We used rats from 5 to 60 postnatal (P) days whose dams were fed a 0% protein diet (PFG) or a normoprotein diet (CG) from P1 to P10. To reproduce the same amount of calorie ingested by the PFG we used an underfed group (UFG). Immunohistochemistry was performed to assess neuropeptide Y (NPY) distribution in the arcuate, periventricular and paraventricular nuclei. Our results showed a NPY immunostaining peak at P10 in all nuclei in CG animals. In UFG animals this peak was observed by P15, while, in the PFG animals only by P20. Our results suggest that the neuropeptidergic arcuate-paraventricular pathway suffered a delay in NPY distribution in undernourished animals, particularly those fed a 0% protein diet, reflecting an effect on this pathway maturation that could explain previously reported alterations on feeding behavior in these animals. PMID:24183962

  9. Arcuate nucleus destruction does not block food deprivation-induced increases in food foraging and hoarding

    PubMed Central

    Dailey, Megan J.; Bartness, Timothy J.

    2010-01-01

    The mechanisms underlying the control of food intake are considerably better understood than those underlying the appetitive ingestive behaviors of foraging and hoarding of food, despite the prevalence of the latter across species including humans. Neuropeptide Y (NPY) and agouti-related protein (AgRP), two orexigenic neuropeptides known to stimulate food intake in a variety of species, applied centrally to Siberian hamsters increases foraging and especially hoarding with lesser increases in food intake. Both are expressed in the arcuate nucleus (Arc) and their synthesis increases with food deprivation, a naturally-occurring stimulus that markedly increases foraging and hoarding in Siberian hamsters. Therefore, we tested whether destruction of Arc neurons blocks these ingestive behaviors. This was accomplished either by microinjecting NPY conjugated to saporin (NPY-SAP) bilaterally into the Arc to kill NPY receptor-bearing neurons or via neonatal monosodium glutamate (MSG) treatment. For both methods, Arc cresyl violet staining (cell density) and NPY and Y1 receptor immunoreactivity (ir) were significantly decreased. Although baseline foraging and food hoarding were not affected, food deprivation-induced increased food hoarding was surprisingly exaggerated ∼100 % with both types of Arc destruction. We found a substantial amount of remaining NPY-ir fibers, likely emanating from the brainstem, and a significant upregulation of Y1 receptors in Arc NPY projections areas (hypothalamic paraventricular nucleus and perifornical area) after Arc denervation and their activation may have accounted for the exaggerated increases. The converging evidence from both Arc destruction methods suggests an intact Arc is not necessary for food deprivation-induced increases in food foraging and hoarding. PMID:20138163

  10. MCT2 Expression and Lactate Influx in Anorexigenic and Orexigenic Neurons of the Arcuate Nucleus

    PubMed Central

    Cortes-Campos, Christian; Elizondo, Roberto; Carril, Claudio; Martínez, Fernando; Boric, Katica; Nualart, Francisco; Garcia-Robles, Maria Angeles

    2013-01-01

    Hypothalamic neurons of the arcuate nucleus control food intake, releasing orexigenic and anorexigenic neuropeptides in response to changes in glucose concentration. Several studies have suggested that the glucosensing mechanism is governed by a metabolic interaction between neurons and glial cells via lactate flux through monocarboxylate transporters (MCTs). Hypothalamic glial cells (tanycytes) release lactate through MCT1 and MCT4; however, similar analyses in neuroendocrine neurons have yet to be undertaken. Using primary rat hypothalamic cell cultures and fluorimetric assays, lactate incorporation was detected. Furthermore, the expression and function of MCT2 was demonstrated in the hypothalamic neuronal cell line, GT1-7, using kinetic and inhibition assays. Moreover, MCT2 expression and localization in the Sprague Dawley rat hypothalamus was analyzed using RT-PCR, in situ hybridization and Western blot analyses. Confocal immunohistochemistry analyses revealed MCT2 localization in neuronal but not glial cells. Moreover, MCT2 was localized to ∼90% of orexigenic and ∼60% of anorexigenic neurons as determined by immunolocalization analysis of AgRP and POMC with MCT2-positives neurons. Thus, MCT2 distribution coupled with lactate uptake by hypothalamic neurons suggests that hypothalamic neurons control food intake using lactate to reflect changes in glucose levels. PMID:23638108

  11. Single-Cell Gene Expression Analysis of Cholinergic Neurons in the Arcuate Nucleus of the Hypothalamus.

    PubMed

    Jeong, Jae Hoon; Woo, Young Jae; Chua, Streamson; Jo, Young-Hwan

    2016-01-01

    The cholinoceptive system in the hypothalamus, in particular in the arcuate nucleus (ARC), plays a role in regulating food intake. Neurons in the ARC contain multiple neuropeptides, amines, and neurotransmitters. To study molecular and neurochemical heterogeneity of ARC neurons, we combine single-cell qRT-PCR and single-cell whole transcriptome amplification methods to analyze expression patterns of our hand-picked 60 genes in individual neurons in the ARC. Immunohistochemical and single-cell qRT-PCR analyses show choline acetyltransferase (ChAT)-expressing neurons in the ARC. Gene expression patterns are remarkably distinct in each individual cholinergic neuron. Two-thirds of cholinergic neurons express tyrosine hydroxylase (Th) mRNA. A large subset of these Th-positive cholinergic neurons is GABAergic as they express the GABA synthesizing enzyme glutamate decarboxylase and vesicular GABA transporter transcripts. Some cholinergic neurons also express the vesicular glutamate transporter transcript gene. POMC and POMC-processing enzyme transcripts are found in a subpopulation of cholinergic neurons. Despite this heterogeneity, gene expression patterns in individual cholinergic cells appear to be highly regulated in a cell-specific manner. In fact, membrane receptor transcripts are clustered with their respective intracellular signaling and downstream targets. This novel population of cholinergic neurons may be part of the neural circuitries that detect homeostatic need for food and control the drive to eat. PMID:27611685

  12. Dopamine/Tyrosine Hydroxylase Neurons of the Hypothalamic Arcuate Nucleus Release GABA, Communicate with Dopaminergic and Other Arcuate Neurons, and Respond to Dynorphin, Met-Enkephalin, and Oxytocin

    PubMed Central

    Zhang, Xiaobing

    2015-01-01

    We employ transgenic mice with selective expression of tdTomato or cre recombinase together with optogenetics to investigate whether hypothalamic arcuate (ARC) dopamine/tyrosine hydroxylase (TH) neurons interact with other ARC neurons, how they respond to hypothalamic neuropeptides, and to test whether these cells constitute a single homogeneous population. Immunostaining with dopamine and TH antisera was used to corroborate targeted transgene expression. Using whole-cell recording on a large number of neurons (n = 483), two types of neurons with different electrophysiological properties were identified in the dorsomedial ARC where 94% of TH neurons contained immunoreactive dopamine: bursting and nonbursting neurons. In contrast to rat, the regular oscillations of mouse bursting neurons depend on a mechanism involving both T-type calcium and A-type potassium channel activation, but are independent of gap junction coupling. Optogenetic stimulation using cre recombinase-dependent ChIEF-AAV-DJ expressed in ARC TH neurons evoked postsynaptic GABA currents in the majority of neighboring dopamine and nondopamine neurons, suggesting for the first time substantial synaptic projections from ARC TH cells to other ARC neurons. Numerous met-enkephalin (mENK) and dynorphin-immunoreactive boutons appeared to contact ARC TH neurons. mENK inhibited both types of TH neuron through G-protein coupled inwardly rectifying potassium currents mediated by δ and μ opioid receptors. Dynorphin-A inhibited both bursting and nonbursting TH neurons by activating κ receptors. Oxytocin excited both bursting and nonbursting neurons. These results reveal a complexity of TH neurons that communicate extensively with neurons within the ARC. SIGNIFICANCE STATEMENT Here, we show that the great majority of mouse hypothalamic arcuate nucleus (ARC) neurons that synthesize TH in the dorsomedial ARC also contain immunoreactive dopamine, and show either bursting or nonbursting electrical activity. Unlike

  13. The Suprachiasmatic Nucleus Modulates the Sensitivity of Arcuate Nucleus to Hypoglycemia in the Male Rat.

    PubMed

    Herrera-Moro Chao, D; León-Mercado, L; Foppen, E; Guzmán-Ruiz, M; Basualdo, M C; Escobar, C; Buijs, R M

    2016-09-01

    The suprachiasmatic nucleus (SCN) and arcuate nucleus (ARC) have reciprocal connections; catabolic metabolic information activates the ARC and inhibits SCN neuronal activity. Little is known about the influence of the SCN on the ARC. Here, we investigated whether the SCN modulated the sensitivity of the ARC to catabolic metabolic conditions. ARC neuronal activity, as determined by c-Fos immunoreactivity, was increased after a hypoglycemic stimulus by 2-deoxyglucose (2DG). The highest ARC neuronal activity after 2DG was found at the end of the light period (zeitgeber 11, ZT11) with a lower activity in the beginning of the light period (zeitgeber 2, ZT2), suggesting the involvement of the SCN. The higher activation of ARC neurons after 2DG at ZT11 was associated with higher 2DG induced blood glucose levels as compared with ZT2. Unilateral SCN-lesioned animals, gave a mainly ipsilateral activation of ARC neurons at the lesioned side, suggesting an inhibitory role of the SCN on ARC neurons. The 2DG-induced counterregulatory glucose response correlated with increased ARC neuronal activity and was significantly higher in unilateral SCN-lesioned animals. Finally, the ARC as site where 2DG may, at least partly, induce a counterregulatory response was confirmed by local microdialysis of 2DG. 2DG administration in the ARC produced a higher increase in circulating glucose compared with 2DG administration in surrounding areas such as the ventromedial nucleus of the hypothalamus (VMH). We conclude that the SCN uses neuronal pathways to the ARC to gate sensory metabolic information to the brain, regulating ARC glucose sensitivity and counterregulatory responses to hypoglycemic conditions. PMID:27429160

  14. Oxytocin nerve fibers innervate beta-endorphin neurons in the arcuate nucleus of the rat hypothalamus.

    PubMed

    Csiffáry, A; Ruttner, Z; Tóth, Z; Palkovits, M

    1992-09-01

    Fine, varicose oxytocin-containing nerve fibers have been demonstrated in the hypothalamic arcuate nucleus in rats. Using Phaseolus vulgaris leukoagglutinin as an anterograde tracer, fine neuronal fibers of paraventricular nucleus origin could be seen throughout the arcuate nucleus. Using double immunostaining, oxytocin-immunoreactive varicose fibers were observed around or in the close vicinity of beta-endorphin-immunoreactive neurons. Silver-gold-labeled oxytocin-immunoreactive presynaptic boutons were shown to make synaptic contacts with diaminobenzidine-labeled beta-endorphin-immunoreactive neurons by electron microscopy. These findings provide morphological evidence for a possible influence of oxytocin on the activity of the brain beta-endorphin system at the hypothalamic level. PMID:1279446

  15. Neuropeptide Y Activity in the Nucleus Accumbens Modulates Feeding Behavior and Neuronal Activity

    PubMed Central

    van den Heuvel, José K.; Furman, Kara; Gumbs, Myrtille C.R.; Eggels, Leslie; Opland, Darren M.; Land, Benjamin B.; Kolk, Sharon M.; Narayanan, Nandakumar; Fliers, Eric; Kalsbeek, Andries; DiLeone, Ralph J.; la Fleur, Susanne E.

    2014-01-01

    Background Neuropeptide Y (NPY) is a hypothalamic neuropeptide that plays a prominent role in feeding and energy homeostasis. Expression of the NPY Y1 receptor (Y1R) is highly concentrated in the nucleus accumbens (Acb), a region important in the regulation of palatable feeding. In this study, we performed a number of experiments to investigate the actions of NPY in the Acb. Methods First, we determined caloric intake and food choice after bilateral administration of NPY in the Acb in rats on a free-choice diet of saturated fat, 30% sucrose solution, and standard chow and whether this was mediated by the Y1R. Second, we measured the effect of intra-Acb NPY on neuronal activity using in vivo electrophysiology. Third, we examined co-localization of Y1R with enkephalin and dynorphin neurons and the effect of NPY on preproenkephalin messenger RNA levels in the striatum using fluorescent and radioactive in situ hybridization. Finally, using retrograde tracing, we examined whether NPY neurons in the arcuate nucleus projected to the Acb. Results In rats on the free-choice, high-fat, high-sugar diet, intra-Acb NPY increased intake of fat, but not sugar or chow, and this was mediated by the Y1R. Intra-Acb NPY reduced neuronal firing, as well as preproenkephalin messenger RNA expression in the striatum. Moreover, Acb enkephalin neurons expressed Y1R and arcuate nucleus NPY neurons projected to the Acb. Conclusions NPY reduces neuronal firing in the Acb resulting in increased palatable food intake. Together, our neuroanatomical, pharmacologic, and neuronal activity data support a role and mechanism for intra-Acb NPY-induced fat intake. PMID:25109664

  16. Homologous upregulation of sst2 somatostatin receptor expression in the rat arcuate nucleus in vivo.

    PubMed

    Tannenbaum, G S; Turner, J; Guo, F; Videau, C; Epelbaum, J; Beaudet, A

    2001-07-01

    In vitro studies using various cell systems have provided conflicting results regarding homologous regulation of somatostatin (SRIH) receptors, and information on whether SRIH regulates the expression of its own receptors in vivo is lacking. In the present study we examined, by in situ hybridization, the effects of pretreatment with the sst2-preferring SRIH analog, octreotide, in vivo, on mRNA levels of two SRIH receptor subtypes, sst1 and sst2, in rat brain and pituitary. (125)I-[DTrp(8)]-SRIH binding was also measured in these regions. Three hours after the iv injection of 50 microg octreotide to conscious adult male rats, there was a 46% increase (p < 0.01) in the labeling density of sst2 mRNA-expressing cells in the hypothalamic arcuate nucleus compared to normal saline-pretreated controls, but not in any of the other brain regions examined. Computer-assisted image analysis revealed that 3 h exposure to octreotide significantly (p < 0.01) augmented both the number and labeling density of sst2 mRNA-expressing cells in the arcuate nucleus, compared to those in saline-treated controls. By contrast, within the anterior pituitary gland, in vivo exposure to octreotide did not affect the expression of sst2 mRNA. No changes in sst1 mRNA-expressing cells were observed after octreotide treatment in any of the regions measured, indicating that the observed effects were homologous, i.e. specific of the receptor subtype stimulated. Octreotide pretreatment was also without effect on the density of (125)I-[DTrp(8)]-SRIH binding in either the arcuate nucleus or pituitary. These results demonstrate, for the first time, that SRIH preexposure in vivo upregulates the expression of a subtype of its own receptors, sst2, within the central nervous system. They further suggest that pretreatment with SRIH in vivo does not cause sst2 receptor desensitization in arcuate nucleus and pituitary. Such homologous regulatory mechanisms may play an important role in the neuroendocrine control

  17. Characterisation of Arcuate Nucleus Kisspeptin/Neurokinin B Neuronal Projections and Regulation during Lactation in the Rat

    PubMed Central

    True, Cadence; Kirigiti, Melissa; Ciofi, Philippe; Grove, Kevin L.; Smith, M. Susan

    2011-01-01

    Lactation results in negative energy balance in the rat leading to decreased gonadotrophin-releasing hormone (GnRH) release and anoestrus. Inhibited GnRH release may be a result of decreased stimulatory tone from neuropeptides critical for GnRH neuronal activity, such as kisspeptin (Kiss1) and neurokinin B (NKB). The present study aimed to identify neuronal projections from the colocalised population of Kiss1/NKB cells in the arcuate nucleus (ARH) using double-label immunohistochemistry to determine where this population may directly regulate GnRH neuronal activity. Additionally, the present study further examined lactation-induced changes in the Kiss1 system that could play a role in decreased GnRH release. The colocalised ARH Kiss1/NKB fibres projected primarily to the internal zone of the median eminence (ME) where they were in close proximity to GnRH fibres; however, few Kiss1/NKB fibres from the ARH were seen at the level of GnRH neurones in the preoptic area (POA). Arcuate Kiss1/NKB peptide levels were decreased during lactation consistent with previous mRNA data. Surprisingly, anteroventral periventricular (AVPV) Kiss1 peptide levels were increased, whereas Kiss1 mRNA levels were decreased during lactation, suggesting active inhibition of peptide release. These findings indicate ARH Kiss1/NKB and AVPV Kiss1 appear to be inhibited during lactation, which may contribute to decreased GnRH release and subsequent reproductive dysfunction. Furthermore, the absence of a strong ARH Kiss1/NKB projection to the POA suggests regulation of GnRH by this population occurs primarily at the ME level via local projections. PMID:21029216

  18. Changes of reactions of neurones in dorsal raphe nucleus and locus coeruleus to electroacupuncture by hypothalamic arcuate nucleus stimulation.

    PubMed

    Yin, Q H; Mao, J R; Guo, S Y

    1988-01-01

    In this experiment the role of the hypothalamic arcuate nucleus (ARC) in acupuncture analgesia and its mechanisms were studied with behavioural and electrophysiological methods. After ARC stimulation the analgesic effect of acupuncture was enhanced significantly and the responses of neurones to electroacupuncture were increased in the dorsal raphe nucleus (DR) and reduced in the locus coeruleus (LC), which could be reversed by intraperitoneal injection of naloxone. The results indicate that ARC might participate in acupuncture analgesia via changing the responses of DR and LC neurones to electroacupuncture, a process in which opiate-like substances (probably beta-endorphin) are involved. PMID:3192102

  19. Research Resource: Gene Profiling of G Protein–Coupled Receptors in the Arcuate Nucleus of the Female

    PubMed Central

    Fang, Yuan; Zhang, Chunguang; Nestor, Casey C.; Mao, Peizhong; Kelly, Martin J.

    2014-01-01

    The hypothalamic arcuate nucleus controls many critical homeostatic functions including energy homeostasis, reproduction, and motivated behavior. Although G protein–coupled receptors (GPCRs) are involved in the regulation of these functions, relatively few of the GPCRs have been identified specifically within the arcuate nucleus. Here, using TaqMan low-density arrays we quantified the mRNA expression of nonolfactory GPCRs in mouse arcuate nucleus. An unprecedented number of GPCRs (total of 292) were found to be expressed, of which 183 were known and 109 were orphan GPCRs. The known GPCR genes expressed were classified into several functional clusters including hormone/neurotransmitter, growth factor, angiogenesis and vasoactivity, inflammation and immune system, and lipid messenger receptors. The plethora of orphan genes expressed in the arcuate nucleus were classified into 5 structure-related classes including class A (rhodopsin-like), class B (adhesion), class C (other GPCRs), nonsignaling 7-transmembrane chemokine-binding proteins, and other 7-transmembrane proteins. Therefore, for the first time, we provide a quantitative estimate of the numerous GPCRs expressed in the hypothalamic arcuate nucleus. Finally, as proof of principle, we documented the expression and function of one of these receptor genes, the glucagon-like peptide 1 receptor (Glp1r), which was highly expressed in the arcuate nucleus. Single-cell RT-PCR revealed that Glp1r mRNA was localized in proopiomelanocortin neurons, and using whole-cell recording we found that the glucagon-like peptide 1-selective agonist exendin-4 robustly excited proopiomelanocortin neurons. Thus, the quantitative GPCR data emphasize the complexity of the hypothalamic arcuate nucleus and furthermore provide a valuable resource for future neuroendocrine/endocrine-related experiments. PMID:24933249

  20. Leptin modulates the intrinsic excitability of AgRP/NPY neurons in the arcuate nucleus of the hypothalamus.

    PubMed

    Baver, Scott B; Hope, Kevin; Guyot, Shannon; Bjørbaek, Christian; Kaczorowski, Catherine; O'Connell, Kristen M S

    2014-04-16

    The hypothalamic arcuate nucleus (ARH) is a brain region critical for regulation of food intake and a primary area for the action of leptin in the CNS. In lean mice, the adipokine leptin inhibits neuropeptide Y (NPY) and agouti-related peptide (AgRP) neuronal activity, resulting in decreased food intake. Here we show that diet-induced obesity in mice is associated with persistent activation of NPY neurons and a failure of leptin to reduce the firing rate or hyperpolarize the resting membrane potential. However, the molecular mechanism whereby diet uncouples leptin's effect on neuronal excitability remains to be fully elucidated. In NPY neurons from lean mice, the Kv channel blocker 4-aminopyridine inhibited leptin-induced changes in input resistance and spike rate. Consistent with this, we found that ARH NPY neurons have a large, leptin-sensitive delayed rectifier K(+) current and that leptin sensitivity of this current is blunted in neurons from diet-induced obese mice. This current is primarily carried by Kv2-containing channels, as the Kv2 channel inhibitor stromatoxin-1 significantly increased the spontaneous firing rate in NPY neurons from lean mice. In HEK cells, leptin induced a significant hyperpolarizing shift in the voltage dependence of Kv2.1 but had no effect on the function of the closely related channel Kv2.2 when these channels were coexpressed with the long isoform of the leptin receptor LepRb. Our results suggest that dynamic modulation of somatic Kv2.1 channels regulates the intrinsic excitability of NPY neurons to modulate the spontaneous activity and the integration of synaptic input onto these neurons in the ARH. PMID:24741039

  1. An intact dorsomedial posterior arcuate nucleus is not necessary for photoperiodic responses in Siberian hamsters.

    PubMed

    Teubner, Brett J W; Leitner, Claudia; Thomas, Michael A; Ryu, Vitaly; Bartness, Timothy J

    2015-04-01

    Seasonal responses of many animal species are triggered by changes in daylength and its transduction into a neuroendocrine signal by the pineal gland through the nocturnal duration of melatonin (MEL) release. The precise central sites necessary to receive, transduce, and relay the short day (SD) fall-winter MEL signals into seasonal responses and changes in physiology and behavior are unclear. In Siberian hamsters, SDs trigger decreases in body and lipid mass, testicular regression and pelage color changes. Several candidate genes and their central sites of expression have been proposed as components of the MEL transduction system with considerable recent focus on the arcuate nucleus (ARC) and its component, the dorsomedial posterior arcuate nucleus (dmpARC). This site has been postulated as a critical relay of SD information through the modulation of a variety of neurochemicals/receptors important for the control of energy balance. Here the necessity of an intact dmpARC for SD responses was tested by making electrolytic lesions of the Siberian hamster dmpARC and then exposing them to either long days (LD) or SDs for 12wks. The SD typical decreases in body and fat mass, food intake, testicular volume, serum testosterone concentrations, pelage color change and increased UCP-1 protein expression (a proxy for brown adipose tissue thermogenesis) all occurred despite the lack of an intact dmpARC. Although the Siberian hamster dmpARC contains photoperiod-modulated constituents, these data demonstrate that an intact dmpARC is not necessary for SD responses and not integral to the seasonal energy- and reproductive-related responses measured here. PMID:25647158

  2. Brain-derived neurotrophic factor is required for axonal growth of selective groups of neurons in the arcuate nucleus

    PubMed Central

    Liao, Guey-Ying; Bouyer, Karine; Kamitakahara, Anna; Sahibzada, Niaz; Wang, Chien-Hua; Rutlin, Michael; Simerly, Richard B.; Xu, Baoji

    2015-01-01

    Objective Brain-derived neurotrophic factor (BDNF) is a potent regulator of neuronal development, and the Bdnf gene produces two populations of transcripts with either a short or long 3′ untranslated region (3′ UTR). Deficiencies in BDNF signaling have been shown to cause severe obesity in humans; however, it remains unknown how BDNF signaling impacts the organization of neuronal circuits that control energy balance. Methods We examined the role of BDNF on survival, axonal projections, and synaptic inputs of neurons in the arcuate nucleus (ARH), a structure critical for the control of energy balance, using Bdnfklox/klox mice, which lack long 3′ UTR Bdnf mRNA and develop severe hyperphagic obesity. Results We found that a small fraction of neurons that express the receptor for BDNF, TrkB, also expressed proopiomelanocortin (POMC) or neuropeptide Y (NPY)/agouti-related protein (AgRP) in the ARH. Bdnfklox/klox mice had normal numbers of POMC, NPY, and TrkB neurons in the ARH; however, retrograde labeling revealed a drastic reduction in the number of ARH axons that project to the paraventricular hypothalamus (PVH) in these mice. In addition, fewer POMC and AgRP axons were found in the dorsomedial hypothalamic nucleus (DMH) and the lateral part of PVH, respectively, in Bdnfklox/klox mice. Using immunohistochemistry, we examined the impact of BDNF deficiency on inputs to ARH neurons. We found that excitatory inputs onto POMC and NPY neurons were increased and decreased, respectively, in Bdnfklox/klox mice, likely due to a compensatory response to marked hyperphagia displayed by the mutant mice. Conclusion This study shows that the majority of TrkB neurons in the ARH are distinct from known neuronal populations and that BDNF plays a critical role in directing projections from these neurons to the DMH and PVH. We propose that hyperphagic obesity due to BDNF deficiency is in part attributable to impaired axonal growth of TrkB-expressing ARH neurons. PMID:26042201

  3. Identification of hypothalamic arcuate nucleus-specific enhancer region of Kiss1 gene in mice.

    PubMed

    Goto, Teppei; Tomikawa, Junko; Ikegami, Kana; Minabe, Shiori; Abe, Hitomi; Fukanuma, Tatsuya; Imamura, Takuya; Takase, Kenji; Sanbo, Makoto; Tomita, Koichi; Hirabayashi, Masumi; Maeda, Kei-ichiro; Tsukamura, Hiroko; Uenoyama, Yoshihisa

    2015-01-01

    Pulsatile secretion of GnRH plays a pivotal role in follicular development via stimulating tonic gonadotropin secretion in mammals. Kisspeptin neurons, located in the arcuate nucleus (ARC), are considered to be an intrinsic source of the GnRH pulse generator. The present study aimed to determine ARC-specific enhancer(s) of the Kiss1 gene by an in vivo reporter assay. Three green fluorescent protein (GFP) reporter constructs (long, medium length, and short) were generated by insertion of GFP cDNA at the Kiss1 locus. Transgenic female mice bearing the long and medium-length constructs showed apparent GFP signals in kisspeptin-immunoreactive cells in both the ARC and anteroventral periventricular nucleus, in which another population of kisspeptin neurons are located. On the other hand, transgenic mice bearing 5'-truncated short construct showed few GFP signals in the ARC kisspeptin-immunoreactive cells, whereas they showed colocalization of GFP- and kisspeptin-immunoreactivities in the anteroventral periventricular nucleus. In addition, chromatin immunoprecipitation and chromosome conformation capture assays revealed recruitment of unoccupied estrogen receptor-α in the 5'-upstream region and intricate chromatin loop formation between the 5'-upstream and promoter regions of Kiss1 locus in the ARC. Taken together, the present results indicate that 5'-upstream region of Kiss1 locus plays a critical role in Kiss1 gene expression in an ARC-specific manner and that the recruitment of estrogen receptor-α and formation of a chromatin loop between the Kiss1 promoter and the 5' enhancer region may be required for the induction of ARC-specific Kiss1 gene expression. These results suggest that the 5'-upstream region of Kiss1 locus functions as an enhancer for ARC Kiss1 gene expression in mice. PMID:25486239

  4. Kisspeptin, neurokinin B, and dynorphin act in the arcuate nucleus to control activity of the GnRH pulse generator in ewes.

    PubMed

    Goodman, Robert L; Hileman, Stanley M; Nestor, Casey C; Porter, Katrina L; Connors, John M; Hardy, Steve L; Millar, Robert P; Cernea, Maria; Coolen, Lique M; Lehman, Michael N

    2013-11-01

    Recent work has led to the hypothesis that kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the arcuate nucleus play a key role in GnRH pulse generation, with kisspeptin driving GnRH release and neurokinin B (NKB) and dynorphin acting as start and stop signals, respectively. In this study, we tested this hypothesis by determining the actions, if any, of four neurotransmitters found in KNDy neurons (kisspeptin, NKB, dynorphin, and glutamate) on episodic LH secretion using local administration of agonists and antagonists to receptors for these transmitters in ovariectomized ewes. We also obtained evidence that GnRH-containing afferents contact KNDy neurons, so we tested the role of two components of these afferents: GnRH and orphanin-FQ. Microimplants of a Kiss1r antagonist briefly inhibited LH pulses and microinjections of 2 nmol of this antagonist produced a modest transitory decrease in LH pulse frequency. An antagonist to the NKB receptor also decreased LH pulse frequency, whereas NKB and an antagonist to the receptor for dynorphin both increased pulse frequency. In contrast, antagonists to GnRH receptors, orphanin-FQ receptors, and the N-methyl-D-aspartate glutamate receptor had no effect on episodic LH secretion. We thus conclude that the KNDy neuropeptides act in the arcuate nucleus to control episodic GnRH secretion in the ewe, but afferent input from GnRH neurons to this area does not. These data support the proposed roles for NKB and dynorphin within the KNDy neural network and raise the possibility that kisspeptin contributes to the control of GnRH pulse frequency in addition to its established role as an output signal from KNDy neurons that drives GnRH pulses. PMID:23959940

  5. Effect of intermittent hypoxia on arcuate nucleus in the leptin-deficient rat.

    PubMed

    Ciriello, John; Moreau, Jason M; McCoy, Aaron; Jones, Douglas L

    2016-07-28

    Intermittent hypoxia (IH) is a major pathophysiological consequence of obstructive sleep apnea. Recently, it has been shown that IH results in changes in body energy balance, leptin secretion and concomitant alterations in arcuate nucleus (ARC). In this study, the role of leptin on these changes was investigated in leptin-deficient rats exposed to IH or normoxic control conditions. Body weights, consumatory and locomotor behaviours, and protein signaling in ARC were assessed immediately after IH exposure. Compared to normoxia, IH altered body weight, food intake, locomotor pattern, and the plasma concentration of leptin and angiotensin II in the wild-type rat. However, these changes were not observed in the leptin-deficient rat. Within ARC of wild-type animals, IH increased phosphorylated signal transducer and activator of transcription 3 and pro-opiomelanocortin protein expression, but not in the leptin-deficient rat. The long-form leptin receptor protein expression was not altered following IH in either rat strain. These data suggest that leptin is involved in mediating the alterations to body energy balance and ARC activity following IH. PMID:27222924

  6. The neuroendocrine genesis of polycystic ovary syndrome: A role for arcuate nucleus GABA neurons.

    PubMed

    Moore, Aleisha M; Campbell, Rebecca E

    2016-06-01

    Polycystic ovary syndrome (PCOS) is a prevalent and distressing endocrine disorder lacking a clearly identified aetiology. Despite its name, PCOS may result from impaired neuronal circuits in the brain that regulate steroid hormone feedback to the hypothalamo-pituitary-gonadal axis. Ovarian function in all mammals is controlled by the gonadotropin-releasing hormone (GnRH) neurons, a small group of neurons that reside in the pre-optic area of the hypothalamus. GnRH neurons drive the secretion of the gonadotropins from the pituitary gland that subsequently control ovarian function, including the production of gonadal steroid hormones. These hormones, in turn, provide important feedback signals to GnRH neurons via a hormone sensitive neuronal network in the brain. In many women with PCOS this feedback pathway is impaired, resulting in the downstream consequences of the syndrome. This review will explore what is currently known from clinical and animal studies about the identity, relative contribution and significance of the individual neuronal components within the GnRH neuronal network that contribute to the pathophysiology of PCOS. We review evidence for the specific neuronal pathways hypothesised to mediate progesterone negative feedback to GnRH neurons, and discuss the potential mechanisms by which androgens may evoke disruptions in these circuits at different developmental time points. Finally, this review discusses data providing compelling support for disordered progesterone-sensitive GABAergic input to GnRH neurons, originating specifically within the arcuate nucleus in prenatal androgen induced forms of PCOS. PMID:26455490

  7. Prolactin regulates kisspeptin neurons in the arcuate nucleus to suppress LH secretion in female rats.

    PubMed

    Araujo-Lopes, Roberta; Crampton, Jessica R; Aquino, Nayara S S; Miranda, Roberta M; Kokay, Ilona C; Reis, Adelina M; Franci, Celso R; Grattan, David R; Szawka, Raphael E

    2014-03-01

    Prolactin (PRL) is known to suppress LH secretion. Kisspeptin neurons regulate LH secretion and express PRL receptors. We investigated whether PRL acts on kisspeptin neurons to suppress LH secretion in lactating (Lac) and virgin rats. Lac rats displayed high PRL secretion and reduced plasma LH and kisspeptin immunoreactivity in the arcuate nucleus (ARC). Bromocriptine-induced PRL blockade significantly increased ARC kisspeptin and plasma LH levels in Lac rats but did not restore them to the levels of non-Lac rats. Bromocriptine effects were prevented by the coadministration of ovine PRL (oPRL). Virgin ovariectomized (OVX) rats treated with either systemic or intracerebroventricular oPRL displayed reduction of kisspeptin expression in the ARC and plasma LH levels, and these effects were comparable with those of estradiol treatment in OVX rats. Conversely, estradiol-treated OVX rats displayed increased kisspeptin immunoreactivity in the anteroventral periventricular nucleus, whereas oPRL had no effect in this brain area. The expression of phosphorylated signal transducer and activator of transcription 5 was used to determine whether kisspeptin neurons in the ARC were responsive to PRL. Accordingly, intracerebroventricular oPRL induced expression of phosphorylated signal transducer and activator of transcription 5 in the great majority of ARC kisspeptin neurons in virgin and Lac rats. We provide here evidence that PRL acts on ARC neurons to inhibit kisspeptin expression in female rats. During lactation, PRL contributes to the inhibition of ARC kisspeptin. In OVX rats, high PRL levels suppress kisspeptin expression and reduce LH release. These findings suggest a pathway through which hyperprolactinemia may inhibit LH secretion and thereby cause infertility. PMID:24456164

  8. Functional expression of P2 purinoceptors in a primary neuroglial cell culture of the rat arcuate nucleus.

    PubMed

    Pollatzek, Eric; Hitzel, Norma; Ott, Daniela; Raisl, Katrin; Reuter, Bärbel; Gerstberger, Rüdiger

    2016-07-01

    The arcuate nucleus (ARC) plays an important role in the hypothalamic control of energy homeostasis. Expression of various purinoceptor subtypes in the rat ARC and physiological studies suggest a modulatory function of P2 receptors within the neuroglial ARC circuitry. A differentiated mixed neuronal and glial microculture was therefore established from postnatal rat ARC, revealing neuronal expression of ARC-specific transmitters involved in food intake regulation (neuropeptide Y (NPY), proopiomelanocortin (POMC), tyrosine hydroxylase (TH)). Some NPYergic neurons cosynthesized TH, while POMC and TH expression proved to be mutually exclusive. Stimulation with the general purinoceptor agonists 2-methylthioadenosine-5'triphosphate (2-MeSATP) and ATP but not the P2X1/P2X3 receptor subtype agonist α,β-methyleneadenosine-5'triphosphate (α,β-meATP) induced intracellular calcium signals in ARC neurons and astrocytes. Some 5-10% each of 2-MeSATP responsive neurons expressed POMC, NYP or TH. Supporting the calcium imaging data, radioligand binding studies to hypothalamic membranes showed high affinity for 2-MeSATP, ATP but not α,β-meATP to displace [α-(35)S]deoxyadenosine-5'thiotriphosphate ([(35)S]dATPαS) from P2 receptors. Repetitive superfusion with equimolar 2-MeSATP allowed categorization of ARC cells into groups with a high or low (LDD) degree of purinoceptor desensitization, the latter allowing further receptor characterization. Calcium imaging experiments performed at 37°C vs. room temperature showed further reduction of desensitization. Agonist-mediated intracellular calcium signals were suppressed in all LDD neurons but only 25% of astrocytes in the absence of extracellular calcium, suggestive of metabotropic P2Y receptor expression in the majority of ARC astrocytes. The highly P2Y1-selective receptor agonists MRS2365 and 2-methylthioadenosine-5'diphosphate (2-MeSADP) activated 75-85% of all 2-MeSATP-responsive ARC astrocytes. Taking into consideration the

  9. Local synaptic release of glutamate from neurons in the rat hypothalamic arcuate nucleus.

    PubMed Central

    Belousov, A B; van den Pol, A N

    1997-01-01

    1. The hypothalamic arcuate nucleus (ARC) contains neuroendocrine neurons that regulate endocrine secretions by releasing substances which control anterior pituitary hormonal release into the portal blood stream. Many neuroactive substances have been identified in the ARC, but the existence of excitatory neurons in the ARC and the identity of an excitatory transmitter have not been investigated physiologically. 2. In the present experiments using whole-cell current- and voltage-clamp recording of neurons from cultures and slices of the ARC, we demonstrate for the first time that some of the neurons in the ARC secrete glutamate as their transmitter. 3. Using microdrop stimulation of presynaptic neurons in ARC slices, we found that local axons from these glutamatergic neurons make local synaptic contact with other neurons in the ARC and that all evoked excitatory postsynaptic potentials could be blocked by the selective ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) and D,L-2-amino-5-phosphonovalerate (AP5; 100 microM). To determine the identity of ARC neurons postsynaptic to local glutamatergic neurons, we used antidromic stimulation to reveal that many of these cells were neuroendocrine neurons by virtue of their maintaining axon terminals in the median eminence. 4. In ARC cultures, postsynaptic potentials, both excitatory and inhibitory, were virtually eliminated by the glutamate receptor antagonists AP5 and CNQX, underlining the functional importance of glutamate within this part of the neuroendocrine brain. 5. GABA was secreted by a subset of ARC neurons from local axons. The GABAA receptor antagonist bicuculline released glutamatergic neurons from chronic inhibition mediated by synaptically released GABA, resulting in further depolarization and an increase in the amplitude and frequency of glutamate-mediated excitatory postsynaptic potentials. Images Figure 1 PMID:9130170

  10. Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol.

    PubMed

    Yasrebi, Ali; Hsieh, Anna; Mamounis, Kyle J; Krumm, Elizabeth A; Yang, Jennifer A; Magby, Jason; Hu, Pu; Roepke, Troy A

    2016-02-15

    Ghrelin's receptor, growth hormone secretagogue receptor (GHSR), is highly expressed in the arcuate nucleus (ARC) and in neuropeptide Y (NPY) neurons. Fasting, diet-induced obesity (DIO), and 17β-estradiol (E2) influence ARC Ghsr expression. It is unknown if these effects occur in NPY neurons. Therefore, we examined the expression of Npy, Agrp, and GHSR signaling pathway genes after fasting, DIO, and E2 replacement in ARC and pools of NPY neurons. In males, fasting increased ARC Ghsr and NPY Foxo1 but decreased NPY Ucp2. In males, DIO decreased ARC and NPY Ghsr and Cpt1c. In fed females, E2 increased Agrp, Ghsr, Cpt1c, and Foxo1 in ARC. In NPY pools, E2 decreased Foxo1 in fed females but increased Foxo1 in fasted females. DIO in females suppressed Agrp and augmented Cpt1c in NPY neurons. In summary, genes involved in GHSR signaling are differentially regulated between the ARC and NPY neurons in a sex-dependent manner. PMID:26577678

  11. Des-Acyl Ghrelin Directly Targets the Arcuate Nucleus in a Ghrelin-Receptor Independent Manner and Impairs the Orexigenic Effect of Ghrelin.

    PubMed

    Fernandez, G; Cabral, A; Cornejo, M P; De Francesco, P N; Garcia-Romero, G; Reynaldo, M; Perello, M

    2016-02-01

    Ghrelin is a stomach-derived octanoylated peptide hormone that plays a variety of well-established biological roles acting via its specific receptor known as growth hormone secretagogue receptor (GHSR). In plasma, a des-octanoylated form of ghrelin, named des-acyl ghrelin (DAG), also exists. DAG is suggested to be a signalling molecule that has specific targets, including the brain, and regulates some physiological functions. However, no specific receptor for DAG has been reported until now, and, consequently, the potential role of DAG as a hormone has remained a matter of debate. In the present study, we show that DAG specifically binds to and acts on a subset of arcuate nucleus (ARC) cells in a GHSR-independent manner. ARC cells labelled by a DAG fluorescent tracer include the neuropeptide Y (NPY) and non-NPY neurones. Given the well-established role of the ARC in appetite regulation, we tested the effect of centrally administered DAG on food intake. We found that DAG failed to affect dark phase feeding, as well as food intake, after a starvation period; however, it impaired the orexigenic actions of peripherally administered ghrelin. Thus, we conclude that DAG directly targets ARC neurones and antagonises the orexigenic effects of peripherally administered ghrelin. PMID:26661382

  12. Transgenic Mice Overexpressing Amyloid Precursor Protein Exhibit Early Metabolic Deficits and a Pathologically Low Leptin State Associated with Hypothalamic Dysfunction in Arcuate Neuropeptide Y Neurons

    PubMed Central

    Ishii, Makoto; Wang, Gang; Racchumi, Gianfranco; Dyke, Jonathan P.

    2014-01-01

    Weight loss is a prominent early feature of Alzheimer's disease (AD) that often precedes the cognitive decline and clinical diagnosis. While the exact pathogenesis of AD remains unclear, accumulation of amyloid-β (Aβ) derived from the amyloid precursor protein (APP) in the brain is thought to lead to the neuronal dysfunction and death underlying the dementia. In this study, we examined whether transgenic mice overexpressing the Swedish mutation of APP (Tg2576), recapitulating selected features of AD, have hypothalamic leptin signaling dysfunction leading to early body weight deficits. We found that 3-month-old Tg2576 mice, before amyloid plaque formation, exhibit decreased weight with markedly decreased adiposity, low plasma leptin levels, and increased energy expenditure without alterations in feeding behavior. The expression of the orexigenic neuropeptide Y (NPY) in the hypothalamus to the low leptin state was abnormal at basal and fasting conditions. In addition, arcuate NPY neurons exhibited abnormal electrophysiological responses to leptin in Tg2576 hypothalamic slices or wild-type slices treated with Aβ. Finally, the metabolic deficits worsened as Tg2576 mice aged and amyloid burden increased in the brain. These results indicate that excess Aβ can potentially disrupt hypothalamic arcuate NPY neurons leading to weight loss and a pathologically low leptin state early in the disease process that progressively worsens as the amyloid burden increases. Collectively, these findings suggest that weight loss is an intrinsic pathological feature of Aβ accumulation and identify hypothalamic leptin signaling as a previously unrecognized pathogenic site of action for Aβ. PMID:24990930

  13. Acute Effects of Capsaicin on Proopioimelanocortin mRNA Levels in the Arcuate Nucleus of Sprague-Dawley Rats

    PubMed Central

    Lee, Jin-Seong; Kim, Hyeun-Kyeung; Baek, Sun-Yong; Kim, Cheol-Min

    2012-01-01

    Objective Capsaicin, a noxious stimulant and main component of the hot flavor of red peppers, has an analgesic effect when administered to humans. We investigated the expression of proopioimelanocortin (POMC) mRNA in the arcuate nucleus of Sprague-Dawley (SD) rats after administering capsaicin, hypothesizing that administering capsaicin activates the central opioid system. Methods SD rats were divided randomly into two groups; one group received a saline injection and the other received a capsaicin injection. The POMC mRNA level in the arcuate nucleus of the hypothalamus was measured by the reverse transcription-polymerase chain reaction at 0, 20, 40, 60, and 120 minutes after capsaicin administration. Results Capsaicin administration resulted in a significantly increased POMC mRNA level, compared to that in saline-treated rats at the 20-minute time point (t=-4.445, p=0.001). However, no significant group differences were observed at other times (t=-1.886, p=0.089; t= -0.973, p=0.353; t=-2.193, p=0.053 for 40, 60, and 120 minutes, respectively). Conclusion The analgesic effect of capsaicin might be associated with increased activity of the cerebral opioid system. This finding suggests that capsaicin acted for nociception and analgesia and could affect alcohol-intake behavior, which might further imply that a food culture could affect drinking behavior. PMID:22707971

  14. An indirect action contributes to c-fos induction in paraventricular hypothalamic nucleus by neuropeptide Y

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neuropeptide Y (NPY) is a well-established orexigenic peptide and hypothalamic paraventricular nucleus (PVH) is one major brain site that mediates the orexigenic action of NPY. NPY induces abundant expression of C-Fos, an indicator for neuronal activation, in the PVH, which has been used extensively...

  15. The effect of hypophysectomy and growth hormone replacement on sst1 and sst2 somatostatin receptor subtype messenger ribonucleic acids in the arcuate nucleus.

    PubMed

    Guo, F; Beaudet, A; Tannenbaum, G S

    1996-09-01

    Although considerable evidence indicates that somatostatin (SRIF) exerts direct actions on GH-releasing hormone-containing arcuate neurons within the hypothalamus to modulate hypophyseal GH secretion, the underlying mechanism(s) remains to be elucidated. We recently demonstrated high levels of expression of the messenger RNAs (mRNAs) coding for two prototypic receptors of the recently cloned SRIF receptor (sst) family, sst1 and sst2, in the arcuate nucleus of the rat hypothalamus. However, information on the biological roles of these receptor subtypes and the factors regulating their expression is lacking. In the present study, we hypothesized that perturbations in GH would influence sst mRNA levels in cells of the arcuate nucleus in vivo. To test this hypothesis, we examined the effects of hypophysectomy (HPX) and HPX with GH replacement, on sst1 and sst2 mRNA levels in the brains of adult male rats by in situ hybridization using 35S-labeled antisense riboprobes. The number of labeled cells and the density of silver grains per cell were quantified using a computer-assisted image analysis system. Two weeks after HPX, there was a 50-60% reduction in both the number and labeling density of sst1 and sst2 mRNA-expressing cells in the arcuate nucleus compared to those in sham-operated control rats. Administration of recombinant human GH (200 micrograms/day for 7 days by continuous sc infusion using osmotic minipumps) to HPX rats augmented both the cell number (P < 0.05) and labeling density (P < 0.01) of sst1 mRNA in the arcuate nucleus, but did not significantly alter sst2 mRNA levels compared to those in HPX rats infused with H2O. There were no significant changes in sst1 and sst2 mRNA levels in extra-arcuate areas, including the cerebral cortex and medial habenula, or in suprachiasmatic, medial preoptic, and magnocellular preoptic nuclei after either HPX or GH replacement. These results indicate that the expression of both sst1 and sst2 SRIF receptor subtypes in

  16. Suprachiasmatic Nucleus Neuropeptides and Their Control of Endogenous Glucose Production.

    PubMed

    Foppen, E; Tan, A A T; Ackermans, M T; Fliers, E; Kalsbeek, A

    2016-04-01

    Defective control of endogenous glucose production is an important factor responsible for hyperglycaemia in the diabetic individual. During the past decade, progressively more evidence has appeared indicating a strong and potentially causal relationship between disturbances of the circadian system and defects of metabolic regulation, including glucose metabolism. The detrimental effects of disturbed circadian rhythms may have their origin in disturbances of the molecular clock mechanisms in peripheral organs, such as the pancreas and liver, or in the central brain clock in the hypothalamic suprachiasmatic nuclei (SCN). To assess the role of SCN output per se on glucose metabolism, we investigated (i) the effect of several SCN neurotransmitters on endogenous glucose production and (ii) the effect of SCN neuronal activity on hepatic and systemic insulin sensitivity. We show that silencing of SCN neuronal activity results in decreased hepatic insulin sensitivity and increased peripheral insulin sensitivity. Furthermore, both oxytocin neurones in the paraventricular nucleus of the hypothalamus (PVN) and orexin neurones in the lateral hypothalamus may be important targets for the SCN control of glucose metabolism. These data further highlight the role of the central clock in the pathophysiology of insulin resistance. PMID:26791158

  17. Neuroplastic changes in the hypothalamic arcuate nucleus: the estradiol effect is accompanied by increased exoendocytotic activity of neuronal membranes.

    PubMed

    Párducz, A; Szilágyi, T; Hoyk, S; Naftolin, F; Garcia-Segura, L M

    1996-04-01

    1. In the rat hypothalamic arcuate nucleus, estradiol induces coordinated changes in the number of axosomatic synapses, the amount of glial ensheathing, and the ultrastructure of the membrane of neuronal somas. In the present study we used conventional electron microscopy and freeze-fracture to examine cellular mechanisms responsible for the estradiol-induced changes at the membrane level. 2. In freeze-fracture replicas taken 10-60 min and 24 hr after injection of 17 beta-estradiol to adult ovariectomized females, it was found that there was a rapid increase in the number of exoendocytotic images that reached a plateau by 30 min. 3. In thin sections from animals injected 24 hr earlier we demonstrated a significant increase in coated vesicles in the periphery of the neurons and coated pits in the perikaryal membranes and decreased axosomatic synapses. 4. We conclude that these morphological alterations are signaling estrogen-induced transport and/or turnover of perikaryal membrane constituents and extracellular components which may affect interneuronal and neuroglial interactions. PMID:8743973

  18. Changes in mRNA expression of arcuate nucleus appetite-regulating peptides during lactation in rats

    PubMed Central

    Suzuki, Yoshihiro; Nakahara, Keiko; Maruyama, Keisuke; Okame, Rieko; Ensho, Takuya; Inoue, Yoshiyuki; Murakami, Noboru

    2014-01-01

    The contribution of hypothalamic appetite-regulating peptides to further hyperphagia accompanying the course of lactation in rats was investigated by using PCR array and real-time PCR. Furthermore, changes in the mRNA expression for appetite-regulating peptides in the hypothalamic arcuate nucleus (ARC) were analyzed at all stages of pregnancy and lactation, and also after weaning. Food intake was significantly higher during pregnancy, lactation, and after weaning than during non-lactation periods. During lactation, ARC expression of mRNAs for agouti-related protein (AgRP) and peptide YY was increased, whereas that of mRNAs for proopiomelanocortin (POMC) and cholecystokinin (CCK) was decreased, in comparison with non-lactation periods. The increase in AgRP mRNA expression during lactation was especially marked. The plasma level of leptin was significantly decreased during the course of lactation, whereas that of acyl-ghrelin was unchanged. In addition, food intake was negatively correlated with the plasma leptin level during lactation. This study has clarified synchronous changes in the expression of many appetite-regulating peptides in ARC of rats during lactation. Our results suggest that hyperphagia during lactation in rats is caused by decreases in POMC and CCK expression and increases in AgRP expression in ARC, the latter being most notable. Together with the decrease in the blood leptin level, such changes in mRNA expression may explain the further hyperphagia accompanying the course of lactation. PMID:24299740

  19. Maternal Obesity in the Mouse Compromises the Blood-Brain Barrier in the Arcuate Nucleus of Offspring.

    PubMed

    Kim, Dong Won; Glendining, Kelly A; Grattan, David R; Jasoni, Christine L

    2016-06-01

    The arcuate nucleus (ARC) regulates body weight in response to blood-borne signals of energy balance. Blood-brain barrier (BBB) permeability in the ARC is determined by capillary endothelial cells (ECs) and tanycytes. Tight junctions between ECs limit paracellular entry of blood-borne molecules into the brain, whereas EC transporters and fenestrations regulate transcellular entry. Tanycytes appear to form a barrier that prevents free diffusion of blood-borne molecules. Here we tested the hypothesis that gestation in an obese mother alters BBB permeability in the ARC of offspring. A maternal high-fat diet model was used to generate offspring from normal-weight (control) and obese dams (OffOb). Evans Blue diffusion into the ARC was higher in OffOb compared with controls, indicating that ARC BBB permeability was altered. Vessels investing the ARC in OffOb had more fenestrations than controls, although the total number of vessels was not changed. A reduced number of tanycytic processes in the ARC of OffOb was also observed. The putative transporters, Lrp1 and dysferlin, were up-regulated and tight junction components were differentially expressed in OffOb compared with controls. These data suggest that maternal obesity during pregnancy can compromise BBB formation in the fetus, leading to altered BBB function in the ARC after birth. PMID:27054554

  20. Phosphorylation of NR2B NMDA subunits by protein kinase C in arcuate nucleus contributes to inflammatory pain in rats

    PubMed Central

    Bu, Fan; Tian, Huiyu; Gong, Shan; Zhu, Qi; Xu, Guang-Yin; Tao, Jin; Jiang, Xinghong

    2015-01-01

    The arcuate nucleus (ARC) of the hypothalamus plays a key role in pain processing. Although it is well known that inhibition of NMDA receptor (NMDAR) in ARC attenuates hyperalgesia induced by peripheral inflammation, the underlying mechanism of NMDAR activation in ARC remains unclear. Protein kinase C (PKC) is involved in several signalling cascades activated in physiological and pathological conditions. Therefore, we hypothesised that upregulation of PKC activates NMDARs in the ARC, thus contributing to inflammatory hyperalgesia. Intra-ARC injection of chelerythrine (CC), a specific PKC inhibitor, attenuated complete Freund’s adjuvant (CFA) induced thermal and mechanical hyperalgesia in a dose-dependent manner. In vivo extracellular recordings showed that microelectrophoresis of CC or MK-801 (a NMDAR antagonist) significantly reduced the enhancement of spontaneous discharges and pain-evoked discharges of ARC neurons. In addition, CFA injection greatly enhanced the expression of total and phosphorylated PKCγ in the ARC. Interestingly, CFA injection also remarkably elevated the level of phosphorylated NR2B (Tyr1472) without affecting the expression of total NR2B. Importantly, intra-ARC injection of CC reversed the upregulation of phosphorylated NR2B subunits in the ARC. Taken together, peripheral inflammation leads to an activation of NMDARs mediated by PKC activation in the ARC, thus producing thermal and mechanical hyperalgesia. PMID:26515544

  1. Silencing of OB-RGRP in mouse hypothalamic arcuate nucleus increases leptin receptor signaling and prevents diet-induced obesity

    PubMed Central

    Couturier, Cyril; Sarkis, Chamsy; Séron, Karin; Belouzard, Sandrine; Chen, Patty; Lenain, Aude; Corset, Laetitia; Dam, Julie; Vauthier, Virginie; Dubart, Anne; Mallet, Jacques; Froguel, Philippe; Rouillé, Yves; Jockers, Ralf

    2007-01-01

    Obesity is a major public health problem and is often associated with type 2 diabetes mellitus, cardiovascular disease, and metabolic syndrome. Leptin is the crucial adipostatic hormone that controls food intake and body weight through the activation of specific leptin receptors (OB-R) in the hypothalamic arcuate nucleus (ARC). However, in most obese patients, high circulating levels of leptin fail to bring about weight loss. The prevention of this “leptin resistance” is a major goal for obesity research. We report here a successful prevention of diet-induced obesity (DIO) by silencing a negative regulator of OB-R function, the OB-R gene-related protein (OB-RGRP), whose transcript is genetically linked to the OB-R transcript. We provide in vitro evidence that OB-RGRP controls OB-R function by negatively regulating its cell surface expression. In the DIO mouse model, obesity was prevented by silencing OB-RGRP through stereotactic injection of a lentiviral vector encoding a shRNA directed against OB-RGRP in the ARC. This work demonstrates that OB-RGRP is a potential target for obesity treatment. Indeed, regulators of the receptor could be more appropriate targets than the receptor itself. This finding could serve as the basis for an approach to identifying potential new therapeutic targets for a variety of diseases, including obesity. PMID:18042720

  2. Estradiol target neurons in the hypothalamic arcuate nucleus and lateral ventromedial nucleus of young adult, reproductively senescent, and monosodium glutamate-lesioned female golden hamsters

    SciTech Connect

    Blaha, G.C.; Lamperti, A.A.

    1983-09-01

    Histoautoradiographic methods were used to assess estrogen target neurons in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus, lateral portion (LVM), comparing young adult and aged female golden hamsters. A subgroup of young adult females had ARC lesions induced by monosodium glutamate at neonatal day 8. All were ovariectomized to remove endogenous estrogens. Controls were given nonradioactive estradiol. After /sup 3/H-estradiol (/sup 3/H-E2) was injected intravenously, hypothalami were removed, frozen, and processed for histoautoradiography. In the ARC and LVM the ratio of /sup 3/H-E2 labelled neurons to total neurons counted was significantly lower in the older animals. Young females with ARC lesions had very few /sup 3/H-E2 labelled neurons remaining in the ARC but had a normal complement in the LVM. Although /sup 3/H-E2 labelled ARC neurons were notably decreased in old females, those ARC neurons that were labelled in the old had virtually the same frequency distribution of the labelling index as in the young, suggesting no change in the average estrogen uptake per target cell.

  3. Testosterone (T)-induced changes in arcuate nucleus cocaine-amphetamine-regulated transcript and NPY mRNA are attenuated in old compared to young male brown Norway rats: contribution of T to age-related changes in cocaine-amphetamine-regulated transcript and NPY gene expression.

    PubMed

    Sohn, Elliott H; Wolden-Hanson, Tami; Matsumoto, Alvin M

    2002-03-01

    The age-related decrease in serum T levels is associated with impairments in food intake and weight regulation and alterations in brain peptides that regulate energy balance. To test the hypothesis that reduced T levels contribute to altered hypothalamic cocaine-amphetamine-regulated transcript (CART) and NPY gene expression, the mRNA content of these neuropeptides was measured by in situ hybridization in sham-operated (intact), castrated, and T-replaced castrated young and old male Brown Norway rats. T levels in T-replaced young and old rats were similar to those in intact young animals. Compared with castrated rats, arcuate nucleus CART mRNA was lower and NPY mRNA was higher in both young and old T-replaced castrated animals, suggesting reciprocal regulation of these peptides by T; these T-induced changes were localized primarily in the rostral arcuate and were markedly attenuated in old animals. Compared with intact animals, paraventricular nucleus CART mRNA was lower in castrated animals and similar in T-replaced young and old rats. We conclude that hypothalamic CART and NPY neurons remain responsive to T regulation in old rats, albeit less so than in young animals, suggesting that the age-related reduction of T contributes in part to altered brain neuropeptide gene expression favoring anorexia and wasting with aging. PMID:11861518

  4. Insulin increases sympathetic nerve activity in part by suppression of tonic inhibitory neuropeptide Y inputs into the paraventricular nucleus in female rats.

    PubMed

    Cassaglia, Priscila A; Shi, Zhigang; Brooks, Virginia L

    2016-07-01

    Following binding to receptors in the arcuate nucleus (ArcN), insulin increases sympathetic nerve activity (SNA) and baroreflex control of SNA via a pathway that includes the paraventricular nucleus of the hypothalamus (PVN). Previous studies in males indicate that the sympathoexcitatory response is mediated by α-melanocyte stimulating hormone (α-MSH), which binds to PVN melanocortin type 3/4 receptors (MC3/4R). The present study was conducted in α-chloralose-anesthetized female rats to test the hypothesis that suppression of inhibitory neuropeptide Y (NPY) inputs to the PVN is also involved. In support of this, blockade of PVN NPY Y1 receptors with BIBO 3304 (NPY1x), ArcN insulin nanoinjections, and PVN NPY1x followed by ArcN insulin each increased lumbar SNA (LSNA) and its baroreflex regulation similarly. Moreover, prior PVN injections of NPY blocked the sympathoexcitatory effects of ArcN insulin. Finally, PVN nanoinjections of the MC3/4R inhibitor SHU9119 prevented both the acute (15 min) and longer, more slowly developing (60 min), increases in LSNA in response to ArcN insulin. In conclusion, in females, ArcN insulin increases LSNA, in part, by suppressing tonic PVN NPY inhibition, which unmasks excitatory α-MSH drive of LSNA. Moreover, the steadily increasing rise in LSNA induced by ArcN insulin is also dependent on PVN MC3/4R. PMID:27122366

  5. Stimulation of the hypothalamic arcuate nucleus increases brown adipose tissue nerve activity via hypothalamic paraventricular and dorsomedial nuclei.

    PubMed

    Chitravanshi, Vineet C; Kawabe, Kazumi; Sapru, Hreday N

    2016-08-01

    Hypothalamic arcuate nucleus (ARCN) stimulation elicited increases in sympathetic nerve activity (IBATSNA) and temperature (TBAT) of interscapular brown adipose tissue (IBAT). The role of hypothalamic dorsomedial (DMN) and paraventricular (PVN) nuclei in mediating these responses was studied in urethane-anesthetized, artificially ventilated, male Wistar rats. In different groups of rats, inhibition of neurons in the DMN and PVN by microinjections of muscimol attenuated the increases in IBATSNA and TBAT elicited by microinjections of N-methyl-d-aspartic acid into the ipsilateral ARCN. In other groups of rats, blockade of ionotropic glutamate receptors by combined microinjections of D(-)-2-amino-7-phosphono-heptanoic acid (D-AP7) and NBQX into the DMN and PVN attenuated increases in IBATSNA and TBAT elicited by ARCN stimulation. Blockade of melanocortin 3/4 receptors in the DMN and PVN in other groups of rats resulted in attenuation of increases in IBATSNA and TBAT elicited by ipsilateral ARCN stimulation. Microinjections of Fluoro-Gold into the DMN resulted in retrograde labeling of cells in the ipsilateral ARCN, and some of these cells contained proopiomelanocortin (POMC), α-melanocyte-stimulating hormone (α-MSH), or vesicular glutamate transporter-3. Since similar projections from ARCN to the PVN have been reported by us and others, these results indicate that neurons containing POMC, α-MSH, and glutamate project from the ARCN to the DMN and PVN. Stimulation of ARCN results in the release of α-MSH and glutamate in the DMN and PVN which, in turn, cause increases in IBATSNA and TBAT. PMID:27402666

  6. Chronic oestradiol reduces the dendritic spine density of KNDy (kisspeptin/neurokinin B/dynorphin) neurones in the arcuate nucleus of ovariectomised Tac2-enhanced green fluorescent protein transgenic mice

    PubMed Central

    Cholanian, Marina; Krajewski-Hall, Sally J.; McMullen, Nathaniel T.; Rance, Naomi E.

    2016-01-01

    Neurones in the arcuate nucleus that express neurokinin B (NKB), kisspeptin and dynorphin (KNDy) play an important role in the reproductive axis. Oestradiol modulates the gene expression and somatic size of these neurones but there is limited information whether their dendritic structure, a correlate of cellular plasticity, is altered by oestrogens. Here we study the morphology of KNDy neurones by filling fluorescent neurones in the arcuate nucleus of Tac2-EGFP transgenic mice with biocytin. Filled neurones from ovariectomized (OVX) or OVX plus 17β-oestradiol (E2)-treated mice were visualized with anti-biotin immunohistochemistry and reconstructed in three dimensions with computer-assisted microscopy. KNDy neurones exhibited two primary dendrites, each with a few branches confined to the arcuate nucleus. Quantitative analysis revealed that E2 treatment of OVX mice decreased the cell size and dendritic spine density of KNDy neurones. The axons of KNDy neurones originated from the cell body or proximal dendrite and gave rise to local branches that appeared to terminate within the arcuate nucleus. Numerous terminal boutons were also visualized within the ependymal layer of the third ventricle adjacent to the arcuate nucleus. Axonal branches also projected to the adjacent median eminence and exited the arcuate nucleus. Confocal microscopy revealed close apposition of EGFP and GnRH-immunoreactive fibers within the median eminence and confirmed the presence of KNDy axon terminals in the ependymal layer of the third ventricle. The axonal branching pattern of KNDy neurones suggests that a single KNDy neurone could influence multiple arcuate neurones, tanycytes in the wall of the third ventricle, axon terminals in the median eminence and numerous areas outside of the arcuate nucleus. In parallel with its inhibitory effects on electrical excitability, E2 treatment of OVX Tac2-EGFP mice induces structural changes in the somata and dendrites of KNDy neurones. PMID:25659412

  7. Peroxisome Proliferator-Activated Receptor γ Controls Ingestive Behavior, Agouti-Related Protein, and Neuropeptide Y mRNA in the Arcuate Hypothalamus

    PubMed Central

    Garretson, John T.; Teubner, Brett J.W.; Grove, Kevin L.; Vazdarjanova, Almira; Ryu, Vitaly

    2015-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is clinically targeted for type II diabetes treatment; however, rosiglitazone (ROSI), a PPARγ agonist, increases food intake and body/fat mass as side-effects. Mechanisms for these effects and the role of PPARγ in feeding are not understood. Therefore, we tested this role in Siberian hamsters, a model of human energy balance, and C57BL/6 mice. We tested the following: (1) how ROSI and/or GW9662 (2-chloro-5-nitro-N-phenylbenzamide; PPARγ antagonist) injected intraperitoneally or into the third ventricle (3V) affected Siberian hamster feeding behaviors; (2) whether food deprivation (FD) co-increases agouti-related protein (AgRP) and PPARγ mRNA expression in Siberian hamsters and mice; (3) whether intraperitoneally administered ROSI increases AgRP and NPY in ad libitum-fed animals; (4) whether intraperitoneally administered PPARγ antagonism blocks FD-induced increases in AgRP and NPY; and finally, (5) whether intraperitoneally administered PPARγ modulation affects plasma ghrelin. Third ventricular and intraperitoneally administered ROSI increased food hoarding and intake for 7 d, an effect attenuated by 3V GW9662, and also prevented (intraperitoneal) FD-induced feeding. FD hamsters and mice increased AgRP within the arcuate hypothalamic nucleus with concomitant increases in PPARγ exclusively within AgRP/NPY neurons. ROSI increased AgRP and NPY similarly to FD, and GW9662 prevented FD-induced increases in AgRP and NPY in both species. Neither ROSI nor GW9662 affected plasma ghrelin. Thus, we demonstrated that PPARγ activation is sufficient to trigger food hoarding/intake, increase AgRP/NPY, and possibly is necessary for FD-induced increases in feeding and AgRP/NPY. These findings provide initial evidence that FD-induced increases in AgRP/NPY may be a direct PPARγ-dependent process that controls ingestive behaviors. PMID:25788674

  8. Peroxisome proliferator-activated receptor γ controls ingestive behavior, agouti-related protein, and neuropeptide Y mRNA in the arcuate hypothalamus.

    PubMed

    Garretson, John T; Teubner, Brett J W; Grove, Kevin L; Vazdarjanova, Almira; Ryu, Vitaly; Bartness, Timothy J

    2015-03-18

    Peroxisome proliferator-activated receptor γ (PPARγ) is clinically targeted for type II diabetes treatment; however, rosiglitazone (ROSI), a PPARγ agonist, increases food intake and body/fat mass as side-effects. Mechanisms for these effects and the role of PPARγ in feeding are not understood. Therefore, we tested this role in Siberian hamsters, a model of human energy balance, and C57BL/6 mice. We tested the following: (1) how ROSI and/or GW9662 (2-chloro-5-nitro-N-phenylbenzamide; PPARγ antagonist) injected intraperitoneally or into the third ventricle (3V) affected Siberian hamster feeding behaviors; (2) whether food deprivation (FD) co-increases agouti-related protein (AgRP) and PPARγ mRNA expression in Siberian hamsters and mice; (3) whether intraperitoneally administered ROSI increases AgRP and NPY in ad libitum-fed animals; (4) whether intraperitoneally administered PPARγ antagonism blocks FD-induced increases in AgRP and NPY; and finally, (5) whether intraperitoneally administered PPARγ modulation affects plasma ghrelin. Third ventricular and intraperitoneally administered ROSI increased food hoarding and intake for 7 d, an effect attenuated by 3V GW9662, and also prevented (intraperitoneal) FD-induced feeding. FD hamsters and mice increased AgRP within the arcuate hypothalamic nucleus with concomitant increases in PPARγ exclusively within AgRP/NPY neurons. ROSI increased AgRP and NPY similarly to FD, and GW9662 prevented FD-induced increases in AgRP and NPY in both species. Neither ROSI nor GW9662 affected plasma ghrelin. Thus, we demonstrated that PPARγ activation is sufficient to trigger food hoarding/intake, increase AgRP/NPY, and possibly is necessary for FD-induced increases in feeding and AgRP/NPY. These findings provide initial evidence that FD-induced increases in AgRP/NPY may be a direct PPARγ-dependent process that controls ingestive behaviors. PMID:25788674

  9. Nutritional Programming of Accelerated Puberty in Heifers: Involvement of Pro-Opiomelanocortin Neurones in the Arcuate Nucleus.

    PubMed

    Cardoso, R C; Alves, B R C; Sharpton, S M; Williams, G L; Amstalden, M

    2015-08-01

    The timing of puberty and subsequent fertility in female mammals are dependent on the integration of metabolic signals by the hypothalamus. Pro-opiomelanocortin (POMC) neurones in the arcuate nucleus (ARC) comprise a critical metabolic-sensing pathway controlling the reproductive neuroendocrine axis. α-Melanocyte-stimulating hormone (αMSH), a product of the POMC gene, has excitatory effects on gonadotrophin-releasing hormone (GnRH) neurones and fibres containing αMSH project to GnRH and kisspeptin neurones. Because kisspeptin is a potent stimulator of GnRH release, αMSH may also stimulate GnRH secretion indirectly via kisspeptin neurones. In the present work, we report studies conducted in young female cattle (heifers) aiming to determine whether increased nutrient intake during the juvenile period (4-8 months of age), a strategy previously shown to advance puberty, alters POMC and KISS1 mRNA expression, as well as αMSH close contacts on GnRH and kisspeptin neurones. In Experiment 1, POMC mRNA expression, detected by in situ hybridisation, was greater (P < 0.05) in the ARC in heifers that gained 1 kg/day of body weight (high-gain, HG; n = 6) compared to heifers that gained 0.5 kg/day (low-gain, LG; n = 5). The number of KISS1-expressing cells in the middle ARC was reduced (P < 0.05) in HG compared to LG heifers. In Experiment 2, double-immunofluorescence showed limited αMSH-positive close contacts on GnRH neurones, and the magnitude of these inputs was not influenced by nutritional status. Conversely, a large number of kisspeptin-immunoreactive cells in the ARC were observed in close proximity to αMSH-containing varicosities. Furthermore, HG heifers (n = 5) exhibited a greater (P < 0.05) percentage of kisspeptin neurones in direct apposition to αMSH fibres and an increased (P < 0.05) number of αMSH close contacts per kisspeptin cell compared to LG heifers (n = 6). These results indicate that the POMC-kisspeptin pathway may be important

  10. Central amygdalar nucleus treated with orexin neuropeptides evoke differing feeding and grooming responses in the hamster.

    PubMed

    Alò, Raffaella; Avolio, Ennio; Mele, Maria; Di Vito, Anna; Canonaco, Marcello

    2015-04-15

    Interaction of the orexinergic (ORXergic) neuronal system with the excitatory (glutamate, l-Glu) or the inhibitory (GABA) neurosignaling complexes evokes major homeostatic physiological events. In this study, effects of the two ORXergic neuropeptides (ORX-A/B) on their receptor (ORX-2R) expression changes were correlated to feeding and grooming actions of the hibernating hamster (Mesocricetus auratus). Infusion of the central amygdala nucleus (CeA) with ORX-A caused hamsters to consume notable quantities of food, while ORX-B accounted for a moderate increase. Interestingly the latter neuropeptide was responsible for greater frequencies of grooming with respect to both controls and the hamsters treated with ORX-A. These distinct behavioral changes turned out to be even greater in the presence of l-Glu agonist (NMDA) while the α1 GABAA receptor agonist (zolpidem, Zol) greatly reduced ORX-A-dependent feeding bouts. Moreover, ORX-A+NMDA mainly promoted greater ORX-2R expression levels with respect to ORX-A-treated hamsters while ORX-B+Zol was instead largely responsible for a down-regulatory trend. Overall, these features point to CeA ORX-2R sites as key sensory limbic elements capable of regulating eating and grooming responses, which may provide useful insights regarding the type of molecular mechanism(s) operating during feeding bouts. PMID:25732800

  11. An in vivo profile of beta-endorphin release in the arcuate nucleus and nucleus accumbens following exposure to stress or alcohol.

    PubMed

    Marinelli, P W; Quirion, R; Gianoulakis, C

    2004-01-01

    The aim of the present study was to determine the effects of distinct categories of stressors on beta-endorphin (beta-EP) release in the arcuate nucleus (ArcN) and nucleus accumbens (NAcb) using in vivo microdialysis. Adult male rats were implanted with a cannula aimed at either the NAcb or the ArcN. On the day of testing, a 2 mm microdialysis probe was inserted into the cannula, and artificial cerebrospinal fluid was infused at 2.0 microl/min. After three baseline collections, animals either had a clothespin applied to the base of their tail for 20 min (a physical/tactile stressor), were exposed to fox urine odour for 20 min (a psychological stressor/species-specific threat), or were administered 2.4 g ethanol/kg body weight, 16.5% w/v, i.p. (a chemical/pharmacological stressor) with control animals receiving an equivalent volume of saline. Both tail-pinch and fox odour significantly increased beta-EP release from the ArcN (P<0.05), whilst only tail-pinch enhanced beta-EP release from the NAcb (P<0.01). On the other hand, alcohol stimulated beta-EP release in the NAcb as compared with saline-treated controls (P<0.01), but not in the ArcN. Although the increase in extracellular beta-EP produced by the other stressors was relatively rapid, there was a 90-min delay before alcohol administration caused beta-EP levels to exceed that of saline-injected controls. In conclusion, the fact that physical and fear-inducing psychological stressors stimulate beta-EP release in the ArcN and only physical stressors stimulate beta-EP release in the NAcb, indicates that stressors with different properties are processed differently in the brain. Also, an injection of alcohol caused a delayed increase of beta-EP in the NAcb but not the ArcN, indicating that alcohol may recruit a mechanism that is, at least partially, distinct from stress-related pathways. PMID:15283974

  12. Neuroendocrine-autonomic integration in the paraventricular nucleus: novel roles for dendritically released neuropeptides.

    PubMed

    Stern, J E

    2015-06-01

    Communication between pairs of neurones in the central nervous system typically involves classical 'hard-wired' synaptic transmission, characterised by high temporal and spatial precision. Over the last two decades, however, knowledge regarding the repertoire of communication modalities used in the brain has notably expanded to include less conventional forms, characterised by a diffuse and less temporally precise transfer of information. These forms are best suited to mediate communication among entire neuronal populations, now recognised to be a fundamental process in the brain for the generation of complex behaviours. In response to an osmotic stressor, the hypothalamic paraventricular nucleus (PVN) generates a multimodal homeostatic response that involves orchestrated neuroendocrine (i.e. systemic release of vasopressin) and autonomic (i.e. sympathetic outflow to the kidneys) components. The precise mechanisms that underlie interpopulation cross-talk between these two distinct neuronal populations, however, remain largely unknown. The present review summarises and discusses a series of recent studies that have identified the dendritic release of neuropeptides as a novel interpopulation signalling modality in the PVN. A current working model is described in which it is proposed that the activity-dependent dendritic release of vasopressin from neurosecretory neurones in the PVN acts in a diffusible manner to increase the activity of distant presympathetic neurones, resulting in an integrated sympathoexcitatory population response, particularly within the context of a hyperosmotic challenge. The cellular mechanism underlying this novel form of intercellular communication, as well as its physiological and pathophysiological implications, is discussed. PMID:25546497

  13. Neuropeptide Y acts in the paraventricular nucleus to suppress sympathetic nerve activity and its baroreflex regulation.

    PubMed

    Cassaglia, Priscila A; Shi, Zhigang; Li, Baoxin; Reis, Wagner L; Clute-Reinig, Nicholas M; Stern, Javier E; Brooks, Virginia L

    2014-04-01

    Neuropeptide Y (NPY), a brain neuromodulator that has been strongly implicated in the regulation of energy balance, also acts centrally to inhibit sympathetic nerve activity (SNA); however, the site and mechanism of action are unknown. In chloralose-anaesthetized female rats, nanoinjection of NPY into the paraventricular nucleus of the hypothalamus (PVN) dose-dependently suppressed lumbar SNA (LSNA) and its baroreflex regulation, and these effects were blocked by prior inhibition of NPY Y1 or Y5 receptors. Moreover, PVN injection of Y1 and Y5 receptor antagonists in otherwise untreated rats increased basal and baroreflex control of LSNA, indicating that endogenous NPY tonically inhibits PVN presympathetic neurons. The sympathoexcitation following blockade of PVN NPY inhibition was eliminated by prior PVN nanoinjection of the melanocortin 3/4 receptor inhibitor SHU9119. Moreover, presympathetic neurons, identified immunohistochemically using cholera toxin b neuronal tract tracing from the rostral ventrolateral medulla (RVLM), express NPY Y1 receptor immunoreactivity, and patch-clamp recordings revealed that both NPY and α-melanocyte-stimulating hormone (α-MSH) inhibit and stimulate, respectively, PVN-RVLM neurons. Collectively, these data suggest that PVN NPY inputs converge with α-MSH to influence presympathetic neurons. Together these results identify endogenous NPY as a novel and potent inhibitory neuromodulator within the PVN that may contribute to changes in SNA that occur in states associated with altered energy balance, such as obesity and pregnancy. PMID:24535439

  14. Neuroendocrine-Autonomic Integration in the Paraventricular Nucleus: Novel Roles for Dendritically Released Neuropeptides

    PubMed Central

    Stern, J. E.

    2015-01-01

    Communication between pairs of neurones in the central nervous system typically involves classical ‘hard-wired’ synaptic transmission, characterised by high temporal and spatial precision. Over the last two decades, however, knowledge regarding the repertoire of communication modalities used in the brain has notably expanded to include less conventional forms, characterised by a diffuse and less temporally precise transfer of information. These forms are best suited to mediate communication among entire neuronal populations, now recognised to be a fundamental process in the brain for the generation of complex behaviours. In response to an osmotic stressor, the hypothalamic paraventricular nucleus (PVN) generates a multimodal homeostatic response that involves orchestrated neuroendocrine (i.e. systemic release of vasopressin) and autonomic (i.e. sympathetic outflow to the kidneys) components. The precise mechanisms that underlie interpopulation cross-talk between these two distinct neuronal populations, however, remain largely unknown. The present review summarises and discusses a series of recent studies that have identified the dendritic release of neuropeptides as a novel interpopulation signalling modality in the PVN. A current working model is described in which it is proposed that the activity-dependent dendritic release of vasopressin from neurosecretory neurones in the PVN acts in a diffusible manner to increase the activity of distant presympathetic neurones, resulting in an integrated sympathoexcitatory population response, particularly within the context of a hyperosmotic challenge. The cellular mechanism underlying this novel form of intercellular communication, as well as its physiological and pathophysiological implications, is discussed. PMID:25546497

  15. Neuropeptide Y acts in the paraventricular nucleus to suppress sympathetic nerve activity and its baroreflex regulation

    PubMed Central

    Cassaglia, Priscila A; Shi, Zhigang; Li, Baoxin; Reis, Wagner L; Clute-Reinig, Nicholas M; Stern, Javier E; Brooks, Virginia L

    2014-01-01

    Neuropeptide Y (NPY), a brain neuromodulator that has been strongly implicated in the regulation of energy balance, also acts centrally to inhibit sympathetic nerve activity (SNA); however, the site and mechanism of action are unknown. In chloralose-anaesthetized female rats, nanoinjection of NPY into the paraventricular nucleus of the hypothalamus (PVN) dose-dependently suppressed lumbar SNA (LSNA) and its baroreflex regulation, and these effects were blocked by prior inhibition of NPY Y1 or Y5 receptors. Moreover, PVN injection of Y1 and Y5 receptor antagonists in otherwise untreated rats increased basal and baroreflex control of LSNA, indicating that endogenous NPY tonically inhibits PVN presympathetic neurons. The sympathoexcitation following blockade of PVN NPY inhibition was eliminated by prior PVN nanoinjection of the melanocortin 3/4 receptor inhibitor SHU9119. Moreover, presympathetic neurons, identified immunohistochemically using cholera toxin b neuronal tract tracing from the rostral ventrolateral medulla (RVLM), express NPY Y1 receptor immunoreactivity, and patch-clamp recordings revealed that both NPY and α–melanocyte-stimulating hormone (α-MSH) inhibit and stimulate, respectively, PVN–RVLM neurons. Collectively, these data suggest that PVN NPY inputs converge with α-MSH to influence presympathetic neurons. Together these results identify endogenous NPY as a novel and potent inhibitory neuromodulator within the PVN that may contribute to changes in SNA that occur in states associated with altered energy balance, such as obesity and pregnancy. PMID:24535439

  16. Synaptic actions of neuropeptide FF in the rat parabrachial nucleus: interactions with opioid receptors.

    PubMed

    Chen, X; Zidichouski, J A; Harris, K H; Jhamandas, J H

    2000-08-01

    The pontine parabrachial nucleus (PBN) receives both opioid and Neuropeptide FF (NPFF) projections from the lower brain stem and/or the spinal cord. Because of this anatomical convergence and previous evidence that NPFF displays both pro- and anti-opioid activities, this study examined the synaptic effects of NPFF in the PBN and the mechanisms underlying these effects using an in vitro brain slice preparation and the nystatin-perforated patch-clamp recording technique. Under voltage-clamp conditions, NPFF reversibly reduced the evoked excitatory postsynaptic currents (EPSCs) in a dose-dependent fashion. This effect was not accompanied by apparent changes in the holding current, the current-voltage relationship or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced inward currents in the PBN cells. When a paired-pulse protocol was used, NPFF increased the ratio of these synaptic currents. Analysis of miniature EPSCs showed that NPFF caused a rightward shift in the frequency-distribution curve, whereas the amplitude-distribution curve remained unchanged. Collectively, these experiments indicate that NPFF reduces the evoked EPSCs through a presynaptic mechanism of action. The synaptic effects induced by NPFF (5 microM) could not be blocked by the specific mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (1 microM), but application of delta-opioid receptor antagonist Tyr-Tic-Phe-Phe (5 microM) almost completely prevented effects of NPFF. Moreover, the delta-opioid receptor agonist, Deltorphin (1 microM), mimicked the effects as NPFF and also occluded NPFF's actions on synaptic currents. These results indicate that NPFF modulates excitatory synaptic transmission in the PBN through an interaction with presynaptic delta-opioid receptors. These observations provide a cellular basis for NPFF enhancement of the antinociceptive effects consequent to central activation of delta-opioid receptors. PMID:10938301

  17. The ghrelin receptor agonist HM01 mimics the neuronal effects of ghrelin in the arcuate nucleus and attenuates anorexia-cachexia syndrome in tumor-bearing rats.

    PubMed

    Borner, Tito; Loi, Laura; Pietra, Claudio; Giuliano, Claudio; Lutz, Thomas A; Riediger, Thomas

    2016-07-01

    The gastric hormone ghrelin positively affects energy balance by increasing food intake and reducing energy expenditure. Ghrelin mimetics are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to characterize the action of the nonpeptidergic ghrelin receptor agonist HM01 on neuronal function, energy homeostasis and muscle mass in healthy rats and to evaluate its possible usefulness for the treatment of CACS in a rat tumor model. Using extracellular single-unit recordings, we tested whether HM01 mimics the effects of ghrelin on neuronal activity in the arcuate nucleus (Arc). Furthermore, we assessed the effect of chronic HM01 treatment on food intake (FI), body weight (BW), lean and fat volumes, and muscle mass in healthy rats. Using a hepatoma model, we investigated the possible beneficial effects of HM01 on tumor-induced anorexia, BW loss, muscle wasting, and metabolic rate. HM01 (10(-7)-10(-6) M) mimicked the effect of ghrelin (10(-8) M) by increasing the firing rate in 76% of Arc neurons. HM01 delivered chronically for 12 days via osmotic minipumps (50 μg/h) increased FI in healthy rats by 24%, paralleled by increased BW, higher fat and lean volumes, and higher muscle mass. Tumor-bearing rats treated with HM01 had 30% higher FI than tumor-bearing controls and were protected against BW loss. HM01 treatment resulted in higher muscle mass and fat mass. Moreover, tumor-bearing rats reduced their metabolic rate following HM01 treatment. Our studies substantiate the possible therapeutic usefulness of ghrelin receptor agonists like HM01 for the treatment of CACS and possibly other forms of disease-related anorexia and cachexia. PMID:27147616

  18. Optogenetic Stimulation of Arcuate Nucleus Kiss1 Neurons Reveals a Steroid-Dependent Glutamatergic Input to POMC and AgRP Neurons in Male Mice.

    PubMed

    Nestor, Casey C; Qiu, Jian; Padilla, Stephanie L; Zhang, Chunguang; Bosch, Martha A; Fan, Wei; Aicher, Sue A; Palmiter, Richard D; Rønnekleiv, Oline K; Kelly, Martin J

    2016-06-01

    Kisspeptin (Kiss1) neurons are essential for reproduction, but their role in the control of energy balance and other homeostatic functions remains unclear. Proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons, located in the arcuate nucleus (ARC) of the hypothalamus, integrate numerous excitatory and inhibitory inputs to ultimately regulate energy homeostasis. Given that POMC and AgRP neurons are contacted by Kiss1 neurons in the ARC (Kiss1(ARC)) and they express androgen receptors, Kiss1(ARC) neurons may mediate the orexigenic action of testosterone via POMC and/or AgRP neurons. Quantitative PCR analysis of pooled Kiss1(ARC) neurons revealed that mRNA levels for Kiss1 and vesicular glutamate transporter 2 were higher in castrated male mice compared with gonad-intact males. Single-cell RT-PCR analysis of yellow fluorescent protein (YFP) ARC neurons harvested from males injected with AAV1-EF1α-DIO-ChR2:YFP revealed that 100% and 88% expressed mRNAs for Kiss1 and vesicular glutamate transporter 2, respectively. Whole-cell, voltage-clamp recordings from nonfluorescent postsynaptic ARC neurons showed that low frequency photo-stimulation (0.5 Hz) of Kiss1-ChR2:YFP neurons elicited a fast glutamatergic inward current in POMC and AgRP neurons. Paired-pulse, photo-stimulation revealed paired-pulse depression, which is indicative of greater glutamate release, in the castrated male mice compared with gonad-intact male mice. Group I and group II metabotropic glutamate receptor agonists depolarized and hyperpolarized POMC and AgRP neurons, respectively, which was mimicked by high frequency photo-stimulation (20 Hz) of Kiss1(ARC) neurons. Therefore, POMC and AgRP neurons receive direct steroid- and frequency-dependent glutamatergic synaptic input from Kiss1(ARC) neurons in male mice, which may be a critical pathway for Kiss1 neurons to help coordinate energy homeostasis and reproduction. PMID:27093227

  19. Tyrosine hydroxylase- and/or aromatic L-amino acid decarboxylase-expressing neurons in the rat arcuate nucleus: ontogenesis and functional significance.

    PubMed

    Ugrumov, M; Melnikova, V; Ershov, P; Balan, I; Calas, A

    2002-07-01

    This study has evaluated in vivo, ex vivo and in vitro the ontogenesis and functional significance of the neurons of the arcuate nucleus (AN) expressing either individual enzymes of dopamine (DA) synthesis, tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC) as well as both of them in rats from the 17th embryonic day (E) till adulthood. Immunocytochemistry, image analysis, confocal microscopy, high performance liquid chromatography with electrochemical detection and radioimmunoassay were used to solve this problem. Monoenzymatic TH-containing neurons were initially observed on E18 located in the ventrolateral AN whereas the neurons expressing only AADC or both AADC and TH first appeared on E20 in the dorsomedial AN. On E21, the monoenzymatic TH- or AADC-expressing neurons comprised more than 99% of the whole neuron population expressing the DA-synthesizing enzymes. In spite of an extremely small number (<1%) of the neurons expressing both enzymes (DArgic neurons), the dissected AN (ex vivo) and its primary cell culture (in vitro) contained a surprisingly high amount of DA and L-dihydroxyphenylalanine (L-DOPA) which were released in response to membrane depolarization. Furthermore, DA production in the AN of fetuses occurred to be sufficient to provide an inhibitory control of prolactin secretion, as in adults. The above data suggest that DA could be synthesized, at least in the AN of fetuses, by monoenzymatic neurons containing either TH or AADC, in co-operation. This hypothesis may be extended to adult animals as their AN contained the same populations of the neurons expressing DA-synthesizing enzymes as in fetuses though the proportion of true DArgic neurons increased up to 38%. During ontogenesis, the monoenzymatic TH- and AADC-containing neurons established axosomatic and axo-axonal junctions that might facilitate the L-DOPA transport from the former to the latter. Moreover, the monoenzymatic AADC-expressing neurons project their axons to

  20. Direct inhibition of arcuate proopiomelanocortin neurons: a potential mechanism for the orexigenic actions of dynorphin

    PubMed Central

    Zhang, Xiaobing; van den Pol, Anthony N

    2013-01-01

    Dynorphin, an endogenous ligand of kappa (κ) opioid receptors, has multiple roles in the brain, and plays a positive role in energy balance and food intake. However, the mechanism for this is unclear. With immunocytochemistry, we find that axonal dynorphin immunoreactivity in the arcuate nucleus is strong, and that a large number of dynorphin-immunoreactive boutons terminate on or near anorexigenic proopiomelanocortin (POMC) cells. Here we provide evidence from whole-cell patch-clamp recording that dynorphin-A (Dyn-A) directly and dose-dependently inhibits arcuate nucleus POMC neurons. Dyn-A inhibition was eliminated by the κ opioid receptor antagonist nor-BNI, but not by the μ receptor antagonist CTAP. The inhibitory effect was mimicked by the κ2 receptor agonist GR89696, but not by the κ1 receptor agonist U69593. No presynaptic effect of κ2 agonists was found. These results suggest that Dyn-A inhibits POMC neurons through activation of the κ2 opioid receptor. In whole-cell voltage clamp, Dyn-A opened G-protein-coupled inwardly rectifying potassium (GIRK)-like channels on POMC neurons. Dynorphin attenuated glutamate and GABA neurotransmission to POMC neurons. In contrast to the strong inhibition of POMC neurons by Dyn-A, we found a weaker direct inhibitory effect of Dyn-A on arcuate nucleus neuropeptide Y (NPY) neurons mediated by both κ1 and κ2 receptors. Taken together, these results indicate a direct inhibitory effect of Dyn-A on POMC neurons through activation of the κ2 opioid receptor and GIRK channels. A number of orexigenic hypothalamic neurons release dynorphin along with other neuropeptides. The inhibition of anorexigenic POMC neurons may be one mechanism underlying the orexigenic actions of dynorphin. PMID:23318874

  1. Neuropeptide W

    PubMed Central

    Takenoya, Fumiko; Kageyama, Haruaki; Hirako, Satoshi; Ota, Eiji; Wada, Nobuhiro; Ryushi, Tomoo; Shioda, Seiji

    2012-01-01

    Neuropeptide W (NPW), which was first isolated from the porcine hypothalamus, exists in two forms, consisting of 23 (NPW23) or 30 (NPW30) amino acids. These neuropeptides bind to one of two NPW receptors, either NPBWR1 (otherwise known as GPR7) or NPBWR2 (GPR8), which belong to the G protein-coupled receptor family. GPR7 is expressed in the brain and peripheral organs of both humans and rodents, whereas GPR8 is not found in rodents. GPR7 mRNA in rodents is widely expressed in several hypothalamic regions, including the paraventricular, supraoptic, ventromedial, dorsomedial, suprachiasmatic, and arcuate nuclei. These observations suggest that GPR7 plays a crucial role in the modulation of neuroendocrine function. The intracerebroventricular infusion of NPW has been shown to suppress food intake and body weight and to increase both heat production and body temperature, suggesting that NPW functions as an endogenous catabolic signaling molecule. Here we summarize our current understanding of the distribution and function of NPW in the brain. PMID:23267349

  2. The paraventricular nucleus of the hypothalamus is a neuroanatomical substrate for the inhibition of palatable food intake by neuropeptide S.

    PubMed

    Fedeli, Amalia; Braconi, Simone; Economidou, Daina; Cannella, Nazzareno; Kallupi, Marsida; Guerrini, Remo; Calò, Girolamo; Cifani, Carlo; Massi, Maurizio; Ciccocioppo, Roberto

    2009-10-01

    Neuropeptide S (NPS) is a recently discovered neurotransmitter that binds to its cognate G-protein coupled receptor, NPSR. Previous studies have shown that central administration of this peptide induces anxiolytic-like effects, promotes arousal and inhibits feeding in the same dose range. In the present study, we sought to investigate further the unique physiopharmacological profile of the NPS system by characterizing its effects on palatable food consumption in rats and comparing it with the effect of the classical anxiolytic benzodiazepine midazolam. The results demonstrated that midazolam (5.0 or 10.0 mg/kg) increases palatable food consumption, while intracerebroventricular (ICV) administration of NPS markedly reduces it. The anorectic effect of NPS (0.1-1.0 nmol per rat, ICV) was prevented by ICV pretreatment with the NPSR antagonist [D-Cys(tBU)(5)]NPS (20.0-60.0 nmol per rat). Pretreatment with the nonselective corticotrophin-releasing factor receptor (CRF) antagonist alpha-helical CRF 9-41 (6.25 and 12.5 nmol per rat) completely reversed the hypophagic action of CRF (0.4 nmol per rat, ICV) but did not prevent the anorectic effect of ICV NPS (1.0 nmol per rat). Brain site-specific microinjection experiments revealed that NPS markedly inhibits palatable food intake if administered into the paraventricular nucleus of the hypothalamus (PVN). A similar but smaller and shorter lasting reduction of feeding was observed following intra-lateral hypothalamus administration, whereas no effect was observed following injection into the central amygdala. The present study demonstrates that NPS evokes a potent inhibition of palatable food consumption and that the PVN is an important site of action for its effect. PMID:19821837

  3. Neuropeptide Y response to alcohol is altered in nucleus accumbens of mice selectively bred for drinking to intoxication.

    PubMed

    Barkley-Levenson, Amanda M; Ryabinin, Andrey E; Crabbe, John C

    2016-04-01

    The High Drinking in the Dark (HDID) mice have been selectively bred for drinking to intoxicating blood alcohol levels and represent a genetic model of risk for binge-like drinking. Presently, little is known about the specific genetic factors that promote excessive intake in these mice. Previous studies have identified neuropeptide Y (NPY) as a potential target for modulating alcohol intake. NPY expression differs in some rodent lines that have been selected for high and low alcohol drinking phenotypes, as well as inbred mouse strains that differ in alcohol preference. Alcohol drinking and alcohol withdrawal also produce differential effects on NPY expression in the brain. Here, we assessed brain NPY protein levels in HDID mice of two replicates of selection and control heterogeneous stock (HS) mice at baseline (water drinking) and after binge-like alcohol drinking to determine whether selection is associated with differences in NPY expression and its sensitivity to alcohol. NPY levels did not differ between HDID and HS mice in any brain region in the water-drinking animals. HS mice showed a reduction in NPY levels in the nucleus accumbens (NAc) - especially in the shell - in ethanol-drinking animals vs. water-drinking controls. However, HDID mice showed a blunted NPY response to alcohol in the NAc core and shell compared to HS mice. These findings suggest that the NPY response to alcohol has been altered by selection for drinking to intoxication in a region-specific manner. Thus, the NPY system may represent a potential target for altering binge-like alcohol drinking in these mice. PMID:26779672

  4. Androgen Receptors in the Posterior Bed Nucleus of the Stria Terminalis Increase Neuropeptide Expression and the Stress-Induced Activation of the Paraventricular Nucleus of the Hypothalamus

    PubMed Central

    Bingham, Brenda; Myung, Clara; Innala, Leyla; Gray, Megan; Anonuevo, Adam; Viau, Victor

    2011-01-01

    The posterior bed nuclei of the stria terminalis (BST) are important neural substrate for relaying limbic influences to the paraventricular nucleus (PVN) of the hypothalamus to inhibit hypothalamic-pituitary-adrenal (HPA) axis responses to emotional stress. Androgen receptor-expressing cells within the posterior BST have been identified as projecting to the PVN region. To test a role for androgen receptors in the posterior BST to inhibit PVN motor neurons, we compared the effects of the non-aromatizable androgen dihydrotestosterone (DHT), the androgen receptor antagonist hydroxyflutamide (HF), or a combination of both drugs implanted unilaterally within the posterior BST. Rats bearing unilateral implants were analyzed for PVN Fos induction in response to acute-restraint stress and relative levels of corticotrophin-releasing hormone and arginine vasopressin (AVP) mRNA. Glutamic acid decarboxylase (GAD) 65 and GAD 67 mRNA were analyzed in the posterior BST to test a local involvement of GABA. There were no changes in GAD expression to support a GABA-related mechanism in the BST. For PVN neuropeptide expression and Fos responses, basic effects were lateralized to the sides of the PVN ipsilateral to the implants. However, opposite to our expectations of an inhibitory influence of androgen receptors in the posterior BST, PVN AVP mRNA and stress-induced Fos were augmented in response to DHT and attenuated in response to HF. These results suggest that a subset of androgen receptor-expressing cells within the posterior BST region may be responsible for increasing the biosynthetic capacity and stress-induced drive of PVN motor neurons. PMID:21412226

  5. Neuropeptide derivatives to regulate the reproductive axis: Kisspeptin receptor (KISS1R) ligands and neurokinin-3 receptor (NK3R) ligands.

    PubMed

    Oishi, Shinya; Fujii, Nobutaka

    2016-11-01

    Recent research has indicated pivotal roles for neuropeptides and their cognate receptors in reproductive physiology. Kisspeptins are RF-amide neuropeptides that stimulate gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus. Neurokinin B (NKB) is a member of the tachykinin family of neuropeptides and positively regulates pulsatile GnRH secretion. These peptides are coexpressed in kisspeptin/NKB/Dyn (KNDy) neurons of the arcuate nucleus, where they contribute to the regulation of puberty onset and other reproductive functions. In this review, the design of peptide ligands for the kisspeptin (KISS1R) and neurokinin-3 (NK3R) receptors are described. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 588-597, 2016. PMID:27271543

  6. Impact of glucose infusion on the structural and functional characteristics of adipose tissue and on hypothalamic gene expression for appetite regulatory neuropeptides in the sheep fetus during late gestation

    PubMed Central

    Mühlhäusler, BS; Adam, CL; Marrocco, EM; Findlay, PA; Roberts, CT; McFarlane, JR; Kauter, KG; McMillen, IC

    2005-01-01

    In the present study, our aim was to determine whether intrafetal glucose infusion increases fetal adiposity, synthesis and secretion of leptin and regulates gene expression of the ‘appetite regulatory’ neuropeptides neuropepetide Y (NPY), agouti-related peptide (AGRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) and receptors (leptin receptor (OB-Rb) and melancortin 3 receptor (MC3R)) within the fetal hypothalamus. Glucose (50% dextrose in saline) or saline was infused (7.5 ml h−1) into fetal sheep between 130 and 140 days gestation (term = 150 ± 3 days gestation). Glucose infusion increased circulating glucose and insulin concentrations, mean lipid locule size (532.8 ± 3.3 μm2 versus 456.7 ± 14.8 μm2) and total unilocular fat mass (11.7 ± 0.6 g versus 8.9 ± 0.6 g) of the perirenal fat depot. The expression of OB-Rb mRNA was higher in the ventromedial nucleus compared to the arcuate nucleus of the hypothalamus in both glucose and saline infused fetuses (F= 8.04; P < 0.01) and there was a positive correlation between expression of OB-Rb and MC3R mRNA in the arcuate nucleus (r= 0.81; P < 0.005). Glucose infusion increased mRNA expression for POMC, but not for the anorectic neuropeptide CART, or the orexigenic neuropeptides NPY and AGRP, in the arcuate nucleus of the fetal hypothalamus. These findings demonstrate that increased circulating glucose and insulin regulate gene expression of the neuropeptides within the fetal hypothalamus that are part of the neural network regulating energy balance in adult life. PMID:15661821

  7. Increased Neurokinin B (Tac2) Expression in the Mouse Arcuate Nucleus Is an Early Marker of Pubertal Onset with Differential Sensitivity to Sex Steroid-Negative Feedback than Kiss1

    PubMed Central

    Navarro, Víctor M.; Kwong, Cecilia; Noel, Sekoni D.; Martin, Cecilia; Xu, Shuyun; Clifton, Donald K.; Carroll, Rona S.; Steiner, Robert A.; Kaiser, Ursula B.

    2012-01-01

    At puberty, neurokinin B (NKB) and kisspeptin (Kiss1) may help to amplify GnRH secretion, but their precise roles remain ambiguous. We tested the hypothesis that NKB and Kiss1 are induced as a function of pubertal development, independently of the prevailing sex steroid milieu. We found that levels of Kiss1 mRNA in the arcuate nucleus (ARC) are increased prior to the age of puberty in GnRH/sex steroid-deficient hpg mice, yet levels of Kiss1 mRNA in wild-type mice remained constant, suggesting that sex steroids exert a negative feedback effect on Kiss1 expression early in development and across puberty. In contrast, levels of Tac2 mRNA, encoding NKB, and its receptor (NK3R; encoded by Tacr3) increased as a function of puberty in both wild-type and hpg mice, suggesting that during development Tac2 is less sensitive to sex steroid-dependent negative feedback than Kiss1. To compare the relative responsiveness of Tac2 and Kiss1 to the negative feedback effects of gonadal steroids, we examined the effect of estradiol (E2) on Tac2 and Kiss1 mRNA and found that Kiss1 gene expression was more sensitive than Tac2 to E2-induced inhibition at both juvenile and adult ages. This differential estrogen sensitivity was tested in vivo by the administration of E2. Low levels of E2 significantly suppressed Kiss1 expression in the ARC, whereas Tac2 suppression required higher E2 levels, supporting differential sensitivity to E2. Finally, to determine whether inhibition of NKB/NK3R signaling would block the onset of puberty, we administered an NK3R antagonist to prepubertal (before postnatal d 30) females and found no effect on markers of pubertal onset in either WT or hpg mice. These results indicate that the expression of Tac2 and Tacr3 in the ARC are markers of pubertal activation but that increased NKB/NK3R signaling alone is insufficient to trigger the onset of puberty in the mouse. PMID:22893725

  8. The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5-HT1B receptors

    PubMed Central

    Duncan, Marilyn J.; Hester, James M.; Hopper, Jason A.; Franklin, Kathleen M.

    2010-01-01

    Age-related changes in circadian rhythms, including attenuation of photic phase shifts, are associated with changes in the central pacemaker in the suprachiasmatic nucleus (SCN). Aging decreases expression of mRNA for vasoactive intestinal peptide (VIP), a key neuropeptide for rhythm generation and photic phase shifts, and increases expression of serotonin transporters and 5-HT1B receptors, whose activation inhibits these phase shifts. Here we describe studies in hamsters showing that aging decreases SCN expression of mRNA for gastrin-releasing peptide, which also modulates photic phase resetting. Because serotonin innervation trophically supports SCN VIP mRNA expression, and serotonin transporters decrease extracellular serotonin, we predicted that chronic administration of the serotonin-selective reuptake inhibitor, fluoxetine, would attenuate the age-related changes in SCN VIP mRNA expression and 5-HT1B receptors. In situ hybridization studies showed that fluoxetine treatment does not alter SCN VIP mRNA expression, in either age group, at zeitgeber time (ZT)6 or 13 (ZT12 corresponds to lights off). However, receptor autoradiographic studies showed that fluoxetine prevents the age-related increase in SCN 5-HT1B receptors at ZT6, and decreases SCN 5-HT1B receptors in both ages at ZT13. Therefore, aging effects on SCN VIP mRNA and SCN 5-HT1B receptors are differentially regulated; the age-related increase in serotonin transporter sites mediates the latter but not the former. The studies also showed that aging and chronic fluoxetine treatment decrease total daily wheel running without altering the phase of the circadian wheel running rhythm, in contrast to previous reports of phase resetting by acute fluoxetine treatment. PMID:20525077

  9. Neuropeptide Y and Agouti-Related Peptide Mediate Complementary Functions of Hyperphagia and Reduced Energy Expenditure in Leptin Receptor Deficiency

    PubMed Central

    Luo, Na; Marcelin, Genevieve; Liu, Shun Mei; Schwartz, Gary

    2011-01-01

    Neuropeptide Y (NPY) and agouti-related peptide (AGRP) can produce hyperphagia, reduce energy expenditure, and promote triglyceride deposition in adipose depots. As these two neuropeptides are coexpressed within the hypothalamic arcuate nucleus and mediate a major portion of the obesity caused by leptin signaling deficiency, we sought to determine whether the two neuropeptides mediated identical or complementary actions. Because of separate neuropeptide receptors and signal transduction mechanisms, there is a possibility of distinct encoding systems for the feeding and energy expenditure aspects of leptin-regulated metabolism. We have genetically added NPY deficiency and/or AGRP deficiency to LEPR deficiency isolated to AGRP cells. Our results indicate that the obesity of LEPR deficiency in AGRP/NPY neurons can produce obesity with either AGRP or NPY alone with AGRP producing hyperphagia while NPY promotes reduced energy expenditure. The absence of both NPY and AGRP prevents the development of obesity attributable to isolated LEPR deficiency in AGRP/NPY neurons. Operant behavioral testing indicated that there were no alterations in the reward for a food pellet from the AGRP-specific LEPR deficiency. PMID:21285324

  10. Electrophysiology of Arcuate Neurokinin B Neurons in Female Tac2-EGFP Transgenic Mice

    PubMed Central

    Cholanian, Marina; Krajewski-Hall, Sally J.; Levine, Richard B.; McMullen, Nathaniel T.

    2014-01-01

    Neurons in the arcuate nucleus that coexpress kisspeptin, neurokinin B (NKB), and dynorphin (KNDy neurons) play an important role in the modulation of reproduction by estrogens. Here, we study the anatomical and electrophysiological properties of arcuate NKB neurons in heterozygous female transgenic mice with enhanced green fluorescent protein (EGFP) under the control of the Tac2 (NKB) promoter (Tac2-EGFP mice). The onset of puberty, estrous cyclicity, and serum LH were comparable between Tac2-EGFP and wild-type mice. The location of EGFP-immunoreactive neurons was consistent with previous descriptions of Tac2 mRNA-expressing neurons in the rodent. In the arcuate nucleus, nearly 80% of EGFP neurons expressed pro-NKB-immunoreactivity. Moreover, EGFP fluorescent intensity in arcuate neurons was increased by ovariectomy and reduced by 17β-estradiol (E2) treatment. Electrophysiology of single cells in tissue slices was used to examine the effects of chronic E2 treatment on Tac2-EGFP neurons in the arcuate nucleus of ovariectomized mice. Whole-cell recordings revealed arcuate NKB neurons to be either spontaneously active or silent in both groups. E2 had no significant effect on the basic electrophysiological properties or spontaneous firing frequencies. Arcuate NKB neurons exhibited either tonic or phasic firing patterns in response to a series of square-pulse current injections. Notably, E2 reduced the number of action potentials evoked by depolarizing current injections. This study demonstrates the utility of the Tac2-EGFP mouse for electrophysiological and morphological studies of KNDy neurons in tissue slices. In parallel to E2 negative feedback on LH secretion, E2 decreased the intensity of the EGFP signal and reduced the excitability of NKB neurons in the arcuate nucleus of ovariectomized Tac2-EGFP mice. PMID:24735328

  11. Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking

    PubMed Central

    McClintick, Jeanette N.; McBride, William J.; Bell, Richard L.; Ding, Zheng-Ming; Liu, Yunlong; Xuei, Xiaoling; Edenberg, Howard J.

    2014-01-01

    Alcohol binge-drinking during adolescence is a serious public health concern with long-term consequences. We used RNA sequencing to assess the effects of excessive adolescent ethanol binge-drinking on gene expression in the dorsal raphe nucleus (DRN) of alcohol preferring (P) rats. Repeated binges across adolescence (three 1h sessions across the dark-cycle per day, 5 days per week for 3 weeks starting at 28 days of age; ethanol intakes of 2.5 – 3 g/kg/session) significantly altered the expression of approximately one-third of the detected genes. Multiple neurotransmitter systems were altered, with the largest changes in the serotonin system (21 of 23 serotonin-related genes showed decreased expression) and GABA-A receptors (8 decreased and 2 increased). Multiple neuropeptide systems were also altered, with changes in the neuropeptide Y and corticotropin-releasing hormone systems similar to those associated with increased drinking and decreased resistance to stress. There was increased expression of 21 of 32 genes for potassium channels. Expression of downstream targets of CREB signaling was increased. There were also changes in expression of genes involved in inflammatory processes, axonal guidance, growth factors, transcription factors, and several intracellular signaling pathways. These widespread changes indicate that excessive binge drinking during adolescence alters the functioning of the DRN and likely its modulation of many regions of the central nervous system, including the mesocorticolimbic system. PMID:25542586

  12. Introduction: Invertebrate Neuropeptides XIII

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This publication represents an introduction to the thirteenth in a series of special issues of the Peptides journal dedicated to invertebrate neuropeptides. The issue addresses a number of aspects of invertebrate neuropeptide research including identification of novel invertebrate neuropeptide sequ...

  13. Introduction: Invertebrate Neuropeptides IX

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Abstract This publication represents an introduction to the fifth in a series of special issues of the Peptides journal dedicated to invertebrate neuropeptides. The issue addresses a number of aspects of invertebrate neuropeptide research including identification of novel invertebrate neuropeptide ...

  14. Introduction: Invertebrate Neuropeptides XV

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This publication represents an introduction to the fifteenth in a series of special issues of the Peptides journal dedicated to invertebrate neuropeptides. The issue addresses a number of aspects of invertebrate neuropeptide research including identification of novel invertebrate neuropeptide seque...

  15. Dopamine D1 and D2 Receptor Immunoreactivities in the Arcuate-Median Eminence Complex and their Link to the Tubero-Infundibular Dopamine Neurons

    PubMed Central

    Romero-Fernandez, W.; Borroto-Escuela, D.O.; Vargas-Barroso, V.; Narváez, M.; Di Palma, M.; Agnati, L.F.; Sahd, J. Larriva

    2014-01-01

    Dopamine D1 and D2 receptor immunohistochemistry and Golgi techniques were used to study the structure of the adult rat arcuate-median eminence complex, and determine the distribution of the dopamine D1 and D2 receptor immunoreactivities therein, particularly in relation to the tubero-infundibular dopamine neurons. Punctate dopamine D1 and D2 receptor immunoreactivities, likely located on nerve terminals, were enriched in the lateral palisade zone built up of nerve terminals, while the densities were low to modest in the medial palisade zone. A codistribution of dopamine D1 receptor or dopamine D2 receptor immunoreactive puncta with tyrosine hydroxylase immunoreactive nerve terminals was demonstrated in the external layer. Dopamine D1 receptor but not dopamine D2 receptor immnunoreactivites nerve cell bodies were found in the ventromedial part of the arcuate nucleus and in the lateral part of the internal layer of the median eminence forming a continuous cell mass presumably representing neuropeptide Y immunoreactive nerve cell bodies. The major arcuate dopamine/ tyrosine hydroxylase nerve cell group was found in the dorsomedial part. A large number of tyrosine hydroxylase immunoreactive nerve cell bodies in this region demonstrated punctate dopamine D1 receptor immunoreactivity but only a few presented dopamine D2 receptor immunoreactivity which were mainly found in a substantial number of tyrosine hydroxylase cell bodies of the ventral periventricular hypothalamic nucleus, also belonging to the tuberoinfundibular dopamine neurons. Structural evidence for projections of the arcuate nerve cells into the median eminence was also obtained. Distal axons formed horizontal axons in the internal layer issuing a variable number of collaterals classified into single or multiple strands located in the external layer increasing our understanding of the dopamine nerve terminal networks in this region. Dopamine D1 and D2 receptors may therefore directly and differentially

  16. High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons

    PubMed Central

    Qiu, Jian; Nestor, Casey C; Zhang, Chunguang; Padilla, Stephanie L; Palmiter, Richard D

    2016-01-01

    Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1ARH neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1ARH neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1ARH neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1ARH neurons. We propose that Kiss1ARH neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function. DOI: http://dx.doi.org/10.7554/eLife.16246.001 PMID:27549338

  17. High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons.

    PubMed

    Qiu, Jian; Nestor, Casey C; Zhang, Chunguang; Padilla, Stephanie L; Palmiter, Richard D; Kelly, Martin J; Rønnekleiv, Oline K

    2016-01-01

    Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1(ARH)) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1(ARH) neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1(ARH) neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1(ARH) neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1(ARH) neurons. We propose that Kiss1(ARH) neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function. PMID:27549338

  18. Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion

    PubMed Central

    Han, Su Young; McLennan, Timothy; Czieselsky, Katja; Herbison, Allan E.

    2015-01-01

    Normal reproductive functioning in mammals depends upon gonadotropin-releasing hormone (GnRH) neurons generating a pulsatile pattern of gonadotropin secretion. The neural mechanism underlying the episodic release of GnRH is not known, although recent studies have suggested that the kisspeptin neurons located in the arcuate nucleus (ARN) may be involved. In the present experiments we expressed channelrhodopsin (ChR2) in the ARN kisspeptin population to test directly whether synchronous activation of these neurons would generate pulsatile luteinizing hormone (LH) secretion in vivo. Characterization studies showed that this strategy targeted ChR2 to 70% of all ARN kisspeptin neurons and that, in vitro, these neurons were activated by 473-nm blue light with high fidelity up to 30 Hz. In vivo, the optogenetic activation of ARN kisspeptin neurons at 10 and 20 Hz evoked high amplitude, pulse-like increments in LH secretion in anesthetized male mice. Stimulation at 10 Hz for 2 min was sufficient to generate repetitive LH pulses. In diestrous female mice, only 20-Hz activation generated significant increments in LH secretion. In ovariectomized mice, 5-, 10-, and 20-Hz activation of ARN kisspeptin neurons were all found to evoke LH pulses. Part of the sex difference, but not the gonadal steroid dependence, resulted from differential pituitary sensitivity to GnRH. Experiments in kisspeptin receptor-null mice, showed that kisspeptin was the critical neuropeptide underlying the ability of ARN kisspeptin neurons to generate LH pulses. Together these data demonstrate that synchronized activation of the ARN kisspeptin neuronal population generates pulses of LH. PMID:26443858

  19. Notch/Rbpjκ signaling regulates progenitor maintenance and differentiation of hypothalamic arcuate neurons

    PubMed Central

    Aujla, Paven K.; Naratadam, George T.; Xu, Liwen; Raetzman, Lori T.

    2013-01-01

    The hypothalamic arcuate nucleus (Arc), containing pro-opoiomelanocortin (POMC), neuropeptide Y (NPY) and growth hormone releasing hormone (GHRH) neurons, regulates feeding, energy balance and body size. Dysregulation of this homeostatic mediator underlies diseases ranging from growth failure to obesity. Despite considerable investigation regarding the function of Arc neurons, mechanisms governing their development remain unclear. Notch signaling factors such as Hes1 and Mash1 are present in hypothalamic progenitors that give rise to Arc neurons. However, how Notch signaling controls these progenitor populations is unknown. To elucidate the role of Notch signaling in Arc development, we analyzed conditional loss-of-function mice lacking a necessary Notch co-factor, Rbpjκ, in Nkx2.1-cre-expressing cells (Rbpjκ cKO), as well as mice with expression of the constitutively active Notch1 intracellular domain (NICD) in Nkx2.1-cre-expressing cells (NICD Tg). We found that loss of Rbpjκ results in absence of Hes1 but not of Hes5 within the primordial Arc at E13.5. Additionally, Mash1 expression is increased, coincident with increased proliferation and accumulation of Arc neurons at E13.5. At E18.5, Rbpjκ cKO mice have few progenitors and show increased numbers of differentiated Pomc, NPY and Ghrh neurons. By contrast, NICD Tg mice have increased hypothalamic progenitors, show an absence of differentiated Arc neurons and aberrant glial differentiation at E18.5. Subsequently, both Rbpjκ cKO and NICD Tg mice have changes in growth and body size during postnatal development. Taken together, our results demonstrate that Notch/Rbpjκ signaling regulates the generation and differentiation of Arc neurons, which contribute to homeostatic regulation of body size. PMID:23884446

  20. Relationship of the Chemokine, CXCL12, to Effects of Dietary Fat on Feeding-Related Behaviors and Hypothalamic Neuropeptide Systems

    PubMed Central

    Poon, Kinning; Barson, Jessica R.; Ho, Hui T.; Leibowitz, Sarah F.

    2016-01-01

    The intake of a high fat diet (HFD), in addition to stimulating orexigenic neuropeptides in the hypothalamus while promoting overeating and reducing locomotor behavior, is known to increase inflammatory mediators that modulate neuronal systems in the brain. To understand the involvement of chemokines in the effects of a HFD, we examined in rats whether HFD intake affects a specific chemokine, CXCL12, and its receptors, CXCR4 and CXCR7, in the hypothalamus together with the neuropeptides and whether CXCL12 itself acts similarly to a HFD in stimulating the neuropeptides and altering ingestion and locomotor behavior. Compared to low-fat chow, a HFD for 5 days significantly increased the expression of CXCL12 and its receptors, in both the paraventricular nucleus (PVN) where the neuropeptides enkephalin (ENK) and galanin were also stimulated and the perifornical lateral hypothalamus (PFLH) where orexin (OX) and melanin-concentrating hormone (MCH) were increased. In contrast, the HFD had no impact on expression of CXCL12 or its receptors in the arcuate nucleus (ARC) where the carbohydrate-related peptide, neuropeptide Y (NPY), was suppressed. Analysis of protein levels revealed a similar stimulatory effect of a HFD on CXCL12 levels in the PVN and PFLH, as well as in blood, and an increase in the number of CXCR4-positive cells in the PVN. In the ARC, in contrast, levels of CXCL12 and number of CXCR4-positive cells were too low to measure. When centrally administered, CXCL12 was found to have similar effects to a HFD. Injection of CXCL12 into the third cerebral ventricle immediately anterior to the hypothalamus significantly stimulated the ingestion of a HFD, reduced novelty-induced locomotor activity, and increased expression of ENK in the PVN where the CXCR4 receptors were dense. It had no impact, however, on NPY in the ARC or on OX and MCH in the PFLH where the CXCR4 receptors were not detected. These results, showing CXCL12 in the hypothalamus to be stimulated by a HFD

  1. Distribution, parabrachial region projection, and coexistence of neuropeptide and catecholamine cells of the nucleus of the solitary tract in the pigeon.

    PubMed

    Berk, M L; Smith, S E; Mullins, L A

    1993-01-15

    The chemical nature of the cells of the nucleus of the solitary tract (NTS) that project to the parabrachial nucleus (PB) was investigated in the pigeon by the use of fluorescent bead retrograde tracer and immunofluorescence for the detection of substance P (SP), leucine-enkephalin (LENK), cholecystokinin (CCK), neurotensin (NT), somatostatin (SS), and tyrosine hydroxylase (TH). Cells immunoreactive for CCK were located in subnuclei lateralis dorsalis pars anterior (LDa) and medialis superficialis pars posterior, and caudal NTS (cNTS); 22-26.5% of these cells were double-labeled bilaterally. Immunoreactive SP cells were found in ventral NTS subnuclei; 24-25% of these cells were double-labeled bilaterally. Cells immunoreactive for LENK and NT were concentrated in the anterior NTS; 5.5-7.5% of the LENK cells were double-labeled bilaterally, while 11% (ipsilateral) and 21% (contralateral) of the NT immunoreactive cells were double-labeled. Many SS immunoreactive cells were found in peripherally located subnuclei; 5.5-6.5% of these cells were double-labeled bilaterally. Catecholamine cells were distributed in LDa, peripheral subnuclei, and cNTS; 23% of these cells were double-labeled ipsilaterally and 8.5% contralaterally. A two-color double-labeling immunofluorescence technique revealed many cells immunoreactive for both NT and LENK, only a rare cell immunoreactive for both SS and SP, and no cells immunoreactive for both TH and SP. Cells immunoreactive for SP, CCK, NT, and TH are major contributors to NTS projections to PB. The confinement of these substances to specific NTS subnuclei, which receive visceral sensory information from specific organs, may contribute to the chemical encoding of ascending visceral information. PMID:7680049

  2. Neuropeptides controlling energy balance: orexins and neuromedins

    PubMed Central

    Nixon, Joshua P.; Kotz, Catherine M.; Novak, Colleen M.; Billington, Charles J.; Teske, Jennifer A.

    2016-01-01

    In this section we review the feeding and energy expenditure effects of orexin (also known as hypocretin) and neuromedin. Orexins are multifunctional neuropeptides that affect energy balance by participating in regulation of appetite, arousal, and spontaneous physical activity. Central orexin signaling for all functions originates in the lateral hypothalamus–perifornical area, and is likely functionally differentiated based on site of action and on interacting neural influences. The effect of orexin on feeding is likely related to arousal in some ways, but is nonetheless a separate neural process that depends on interactions with other feeding related neuropeptides. In a pattern distinct from other neuropeptides, orexin stimulates both feeding and energy expenditure. Orexin increases in energy expenditure are mainly by increasing spontaneous physical activity, and this energy expenditure effect is more potent than the effect on feeding. Global orexin manipulations, such as in transgenic models, produce energy balance changes consistent with a dominant energy expenditure effect of orexin. Neuromedins are gut-brain peptides that reduce appetite. There are gut sources of neuromedin, but likely the key appetite related neuromedin producing neurons are in hypothalamus and parallel other key anorectic neuropeptide expression in the arcuate to paraventricular hypothalamic projection. As with other hypothalamic feeding related peptides, hindbrain sites are likely also important sources and targets of neuromedin anorectic action. Neuromedin increases physical activity in addition to reducing appetite, thus producing a consistent negative energy balance effect. Together with the various other neuro-peptides, -transmitters, -modulators and –hormones, neuromedin and orexin act in the appetite network to produce changes in food intake and energy expenditure, which ultimately influences the regulation of body weight. PMID:22249811

  3. Neuropeptide Y system in accumbens shell mediates ethanol self-administration in posterior ventral tegmental area.

    PubMed

    Borkar, Chandrashekhar D; Upadhya, Manoj A; Shelkar, Gajanan P; Subhedar, Nishikant K; Kokare, Dadasaheb M

    2016-07-01

    Although modulatory effects of neuropeptide Y (NPY) on ethanol consumption are well established, its role in ethanol reward, in the framework of mesolimbic dopaminergic system, has not been studied. We investigated the influence of nucleus accumbens shell (AcbSh) NPYergic system on ethanol self-administration in posterior ventral tegmental area (p-VTA) using intracranial self-administration paradigm. Rats were stereotaxically implanted with cannulae targeted unilaterally at the right p-VTA and trained to self-administer ethanol (200 mg%) in standard two-lever (active/inactive) operant chamber, an animal model with high predictive validity to test the rewarding mechanisms. Over a period of 7 days, these rats showed a significant increase in the number of lever presses for ethanol self-administration suggesting reinforcement. While intra-AcbSh NPY (1 or 2 ng/rat) or [Leu(31) , Pro(34) ]-NPY (0.5 or 1 ng/rat) dose-dependently increased ethanol self-administration, BIBP3226 (0.4 or 0.8 ng/rat) produced opposite effect. The rats conditioned to self-administer ethanol showed significant increase in the population of NPY-immunoreactive cells and fibres in the AcbSh, central nucleus of amygdala (CeA), hypothalamic arcuate nucleus (ARC) and lateral part of bed nucleus of stria terminalis as compared with that in the naïve rats. Neuronal tracing studies showed that NPY innervations in the AcbSh may derive from the neurons of ARC and CeA. As NPY and dopamine systems in reward areas are known to interact, we suggest that NPY inputs from ARC and CeA may play an important role in modulation of the dopaminergic system in the AcbSh and consequently influence the ethanol induced reward and addiction. PMID:25929272

  4. Elevated body weight gain during the juvenile period alters neuropeptide Y-gonadotropin-releasing hormone circuitry in prepubertal heifers.

    PubMed

    Alves, Bruna R C; Cardoso, Rodolfo C; Prezotto, Ligia D; Thorson, Jennifer F; Bedenbaugh, Michelle; Sharpton, Sarah M; Caraty, Alain; Keisler, Duane H; Tedeschi, Luis O; Williams, Gary L; Amstalden, Marcel

    2015-02-01

    Increased body weight (BW) gain during the juvenile period leads to early maturation of the reproductive neuroendocrine system. We investigated whether a nutritional regimen that advances the onset of puberty leads to alterations in the hypothalamic neuropeptide Y (NPY) circuitry that are permissive for enhanced gonadotropin-releasing hormone (GnRH) secretion. It was hypothesized that NPY mRNA and NPY projections to GnRH and kisspeptin neurons are reduced in heifers that gain BW at an accelerated rate, compared with a lower one, during the juvenile period. Heifers were weaned at approximately 4 mo of age and fed diets to promote relatively low (0.5 kg/day; low gain [LG]) or high (1.0 kg/day; high gain [HG]) rates of BW gain until 8.5 mo of age. Heifers that gained BW at a higher rate exhibited greater circulating concentrations of leptin and reduced overall NPY expression in the arcuate nucleus. The proportion of GnRH neurons in close apposition to NPY fibers and the magnitude of NPY projections to GnRH neurons located in the mediobasal hypothalamus were reduced in HG heifers. However, no differences in NPY projections to kisspeptin neurons in the arcuate nucleus were detected between HG and LG heifers. Results indicate that a reduction in NPY innervation of GnRH neurons, particularly at the level of the mediobasal hypothalamus, occurs in response to elevated BW gain during the juvenile period. This functional plasticity may facilitate early onset of puberty in heifers. PMID:25505201

  5. Reproductive neuropeptides: prevalence of GnRH and KNDy neural signalling components in a model avian, gallus gallus.

    PubMed

    Joseph, Nerine T; Tello, Javier A; Bedecarrats, Gregoy Y; Millar, Robert P

    2013-09-01

    Diverse external and internal environmental factors are integrated in the hypothalamus to regulate the reproductive system. This is mediated through the pulsatile secretion of GnRH into the portal system to stimulate pituitary gonadotrophin secretion, which in turn regulates gonadal function. A single subpopulation of neurones termed 'KNDy neurones' located in the hypothalamic arcuate nucleus co-localise kisspeptin (Kiss), neurokinin B (NKB) and dynorphin (Dyn) and are responsive to negative feedback effects of sex steroids. The co-ordinated secretion from KNDy neurones appears to modulate the pulsatile release of GnRH, acting as a proximate pacemaker. This review briefly describes the neuropeptidergic control of reproduction in the avian class, highlighting the status of reproductive neuropeptide signalling systems homologous to those found in mammalian genomes. Genes encoding the GnRH system are complete in the chicken with similar roles to the mammalian counterparts, whereas genes encoding Kiss signalling components appear missing in the avian lineage, indicating a differing set of hypothalamic signals controlling avian reproduction. Gene sequences encoding both NKB and Dyn signalling components are present in the chicken genome, but expression analysis and functional studies remain to be completed. The focus of this article is to describe the avian complement of neuropeptidergic reproductive hormones and provide insights into the putative mechanisms that regulate reproduction in birds. These postulations highlight differences in reproductive strategies of birds in terms of gonadal steroid feedback systems, integration of metabolic signals and seasonality. Also included are propositions of KNDy neuropeptide gene silencing and plasticity in utilisation of these neuropeptides during avian evolution. PMID:23756151

  6. Reducing adsorption to improve recovery and in vivo detection of neuropeptides by microdialysis with LC-MS.

    PubMed

    Zhou, Ying; Wong, Jenny-Marie T; Mabrouk, Omar S; Kennedy, Robert T

    2015-10-01

    Neuropeptides are an important class of neurochemicals; however, measuring their concentration in vivo by using microdialysis sampling is challenging due to their low concentration and the small samples generated. Capillary liquid chromatography with mass spectrometry (cLC-MS) can yield attomole limits of detection (LOD); however, low recovery and loss of sample to adsorptive surfaces can still hinder detection of neuropeptides. We have evaluated recovery during sampling and transfer to the cLC column for a selection of 10 neuropeptides. Adding acetonitrile to sample eliminated carryover and improved LOD by 1.4- to 60-fold. The amount of acetonitrile required was found to have an optimal value that correlated with peptide molecular weight and retention time on a reversed phase LC column. Treating AN69 dialysis membrane, which bears negative charge due to incorporated sulfonate groups, with polyethylenimine (PEI) improved recovery by 1.2- to 80-fold. The effect appeared to be due to reducing electrostatic interaction between peptides and the microdialysis probe because modification increased recovery only for peptides that carried net positive charge. The combined effects improved LOD of the entire method by 1.3- to 800-fold for the different peptides. We conclude that peptides with both charged and hydrophobic regions require combined strategies to prevent adsorption and yield the best possible detection. The method was demonstrated by determining orexin A, orexin B, and a novel isoform of rat β-endorphin in the arcuate nucleus. Dialysate concentrations were below 10 pM for these peptides. A standard addition study on dialysates revealed that while some peptides can be accurately quantified, some are affected by the matrix. PMID:26351736

  7. The novel neuropeptide phoenixin is highly co-expressed with nesfatin-1 in the rat hypothalamus, an immunohistochemical study.

    PubMed

    Pałasz, Artur; Rojczyk, Ewa; Bogus, Katarzyna; Worthington, John J; Wiaderkiewicz, Ryszard

    2015-04-10

    The hypothalamus regulates a number of autonomic functions essential for homeostasis; therefore, investigations concerning hypothalamic neuropeptides and their functions and distribution are of great importance in contemporary neuroscience. Recently, novel regulatory factors expressed in the hypothalamus have been discovered, of which nesfatin-1 and phoenixin (PNX), show intriguing similarities in their brain distributions. There are currently few studies characterizing PNX expression, so it is imperative to accurately trace its localization, with particular attention to the hypothalamic nuclei and nesfatin-1 co-expression. Using fluorescence and classical immunohistochemical stainings on adult rat brain, we visualized the potential co-expression of nesfatin-1 and PNX immunoreactive cells. We have demonstrated a distinct PNX-immunoreactivity in 21-32% of cells in the arcuate nucleus, paraventricular nucleus, ventromedial and lateral hypothalamus. Nesfatin-1 expression reached 45-68% of all neurons in the same sites, while co-expression was strikingly seen in the vast majority (70-86%) of PNX-immunoreactive neurons in the rat hypothalamic nuclei. Our results demonstrate for the first time, a wide distribution of PNX in the hypothalamus which could implicate a potential functional relationship with nesfatin-1, possibly in the regulation of the hypothalamic-pituitary-gonadal axis or other autonomic functions, which require further study. PMID:25736948

  8. Effects of opioid antagonists naloxone and naltrexone on neuropeptide Y-induced feeding and brown fat thermogenesis in the rat. Neural site of action.

    PubMed Central

    Kotz, C M; Grace, M K; Briggs, J; Levine, A S; Billington, C J

    1995-01-01

    Neuropeptide Y administered intracerebroventricularly and into the paraventricular nucleus of the hypothalamus stimulates feeding and decreases brown adipose tissue thermogenesis. Although specific neuropeptide Y antagonists are not yet available, previous studies had shown that the opioid antagonist naloxone blocked neuropeptide Y-induced feeding when both drugs were injected intracerebroventricularly. We wanted to find out if naloxone injected into specific brain sites would block neuropeptide Y effects on feeding and brown fat thermogenesis. Rats were double injected in specific brain sites with neuropeptide Y and either naloxone or naltrexone (a congener of naloxone). Food intake and brown fat measures were assessed. Naloxone or naltrexone in the paraventricular nucleus weakly decreased paraventricular nucleus neuropeptide Y-induced feeding and did not affect neuropeptide Y-induced reductions in brown fat activity. Peripheral naloxone blocked intracerebroventricular neuropeptide Y-induced feeding and brown fat alterations. Fourth ventricular naloxone decreased paraventricular nucleus neuropeptide Y-induced feeding, and naltrexone given into the nucleus of the solitary tract blocked paraventricular nucleus neuropeptide Y-induced alterations in feeding and brown fat. These data indicate that neuropeptide Y in the paraventricular nucleus may act on feeding and brown fat thermogenesis through opioidergic pathways in the nucleus of the solitary tract. PMID:7615787

  9. Introduction: Invertebrate Neuropeptides XI

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This publication represents an introduction to the eleventh in a series of special issues of the Peptides journal dedicated to invertebrate neuropeptides. The issue addresses a number of aspects of invertebrate neuropeptide research including identification of novel characterization of new biologic...

  10. Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serotonin 2C receptors (5-HT2CRs) expressed by pro-opiomelanocortin (POMC) neurons of hypothalamic arcuate nucleus regulate food intake, energy homeostasis ,and glucose metabolism. However, the cellular mechanisms underlying the effects of 5-HT to regulate POMC neuronal activity via 5-HT2CRs have no...

  11. Neuropeptide physiology in helminths.

    PubMed

    Mousley, Angela; Novozhilova, Ekaterina; Kimber, Michael J; Day, Tim A

    2010-01-01

    Parasitic worms come from two distinct, distant phyla, Nematoda (roundworms) and Platyhelminthes (flatworms). The nervous systems of worms from both phyla are replete with neuropeptides and there is ample physiological evidence that these neuropeptides control vital aspects of worm biology. In each phyla, the physiological evidence for critical roles for helminth neuropeptides is derived from both parasitic and free-living members. In the nematodes, the intestinal parasite Ascaris suum and the free-living Caenorhabditis elegans have yielded most of the data; in the platyhelminths, the most physiological data has come from the blood fluke Schistosoma mansoni. FMRFamide-like peptides (FLPs) have many varied effects (excitation, relaxation, or a combination) on somatic musculature, reproductive musculature, the pharynx and motor neurons in nematodes. Insulin-like peptides (INSs) play an essential role in nematode dauer formation and other developmental processes. There is also some evidence for a role in somatic muscle control for the somewhat heterogeneous grouping ofpeptides known as neuropeptide-like proteins (NLPs). In platyhelminths, as in nematodes, FLPs have a central role in somatic muscle function. Reports of FLP physiological action in platyhelminths are limited to a potent excitation of the somatic musculature. Platyhelminths are also abundantly endowed with neuropeptide Fs (NPFs), which appear absent from nematodes. There is not yet any data linking platyhelminth NPF to any particular physiological outcome, but this neuropeptide does potently and specifically inhibit cAMP accumulation in schistosomes. In nematodes and platyhelminths, there is an abundance of physiological evidence demonstrating that neuropeptides play critical roles in the biology of both free-living and parasitic helminths. While it is certainly true that there remains a great deal to learn about the biology of neuropeptides in both phyla, physiological evidence presently available points

  12. Localization of neuropeptide-Y immunoreactivity in estradiol-concentrating cells in the hypothalamus

    SciTech Connect

    Sar, M.; Sahu, A.; Crowley, W.R.; Kalra, S.P. )

    1990-12-01

    Considerable evidence shows that gonadal steroids exert a facilitatory influence on levels and release of neuropeptide-Y (NPY) from the hypothalamus. However, it is not known whether gonadal steroids act directly on NPY-producing cells in the arcuate nucleus (ARC) of the hypothalamus to produce these facilitatory effects on NPY or whether they act on other cells that have a modulatory influence via synapses on ARC NPY cells. We applied the combined method of steroid autoradiography and immunocytochemistry to assess the localization of (3H)estradiol in relation to NPY-producing cells in the hypothalamus. Rats (n = 6) were bilaterally ovariectomized and injected intracerebroventricularly with colchicine. Twenty-four hours later each rat received an iv injection of 17 beta-(2,4,6,7,16,17(-3)H)estradiol (SA, 166 Ci/mmol) at a dose of 5.0 micrograms/kg BW. One hour after the injection of (3H)estradiol, the rats were perfused with 4% paraformaldehyde; brains were removed, frozen in isopentane precooled in liquid nitrogen (-190 C), sectioned, and processed for autoradiography. The autoradiograms were then incubated with specific antibodies for NPY immunostaining by the avidin-biotin-peroxidase method. The results revealed NPY-immunopositive cells in the ARC, striatum, hippocampus, amygdala, and cerebral cortex and a few cells in the median eminence. NPY-immunoreactive fibers were also detected in the internal layer of the median eminence. The largest number of neurons showing NPY immunoreactivity in the cytoplasm was detected in the ARC, and only in this nucleus did we observed colocalization of (3H)estradiol and NPY immunoreactivity in neurons. A population of NPY-immunopositive cells in the ARC (10-20%) exhibited nuclear (3H)estradiol; the majority of these cells were located in the lateral and ventral portions of the ARC.

  13. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding

    PubMed Central

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  14. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

    PubMed

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  15. Seasonal changes in body mass, serum leptin levels and hypothalamic neuropeptide gene expression in male Eothenomys olitor.

    PubMed

    Wan-long, Zhu; Zheng-kun, Wang

    2015-06-01

    The present study examined seasonal changes in body mass and energy metabolism in the Chaotung vole (Eothenomys olitor) and the physiological mechanisms underpinning these changes. Seasonal changes in the following parameters were measured in male E. olitor, body mass, food intake, thermogenesis, enzyme activity, masses of tissues and organs, hormone concentrations and expression of hypothalamic arcuate nucleus energy balance genes including neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART). Body mass was constant over the year, but the masses of tissues and organs differed significantly between seasons. There were significant changes in body fat mass and serum leptin levels over the four seasons. E. olitor showed significant seasonal changes in food intake and thermogenesis, uncoupling protein 1 (UCP1) content, enzyme activity, and serum tri-iodothyronine (T3) and thyroxine (T4) levels. Moreover, mRNA expression in the hypothalamus showed significant seasonal changes. All of our results suggested that E. olitor had constant body mass over the year, which was inconsistent with the prediction of the 'set-point' hypothesis. However, body fat mass and serum leptin levels were significantly different among the four seasons, providing support for the 'set-point' hypothesis. The changes in leptin, NPY, AgRP, POMC, and CART mRNA levels may play a role in the regulation of energy intake in E. olitor. Furthermore, the role of leptin and hypothalamic neuropeptide gene in the regulation of energy metabolism and body mass may be different in animals that are acclimated to different seasons. PMID:25700741

  16. Adult exposure to tributyltin affects hypothalamic neuropeptide Y, Y1 receptor distribution, and circulating leptin in mice.

    PubMed

    Bo, E; Farinetti, A; Marraudino, M; Sterchele, D; Eva, C; Gotti, S; Panzica, G

    2016-07-01

    Tributyltin (TBT), a pesticide used in antifouling paints, is toxic for aquatic invertebrates. In vertebrates, TBT may act in obesogen- inducing adipogenetic gene transcription for adipocyte differentiation. In a previous study, we demonstrated that acute administration of TBT induces c-fos expression in the arcuate nucleus. Therefore, in this study, we tested the hypothesis that adult exposure to TBT may alter a part of the nervous pathways controlling animal food intake. In particular, we investigated the expression of neuropeptide Y (NPY) immunoreactivity. This neuropeptide forms neural circuits dedicated to food assumption and its action is mediated by Y1 receptors that are widely expressed in the hypothalamic nuclei responsible for the regulation of food intake and energy homeostasis. To this purpose, TBT was orally administered at a dose of 0.025 mg/kg/day/body weight to adult animals [male and female C57BL/6 (Y1-LacZ transgenic mice] for 4 weeks. No differences were found in body weight and fat deposition, but we observed a significant increase in feed efficiency in TBT-treated male mice and a significant decrease in circulating leptin in both sexes. Computerized quantitative analysis of NPY immunoreactivity and Y1-related β-galactosidase activity demonstrated a statistically significant reduction in NPY and Y1 transgene expression in the hypothalamic circuit controlling food intake of treated male mice in comparison with controls. In conclusion, the present results indicate that adult exposure to TBT is profoundly interfering with the nervous circuits involved in the stimulation of food intake. PMID:27310180

  17. Effects of long-term ingestion of aspartame on hypothalamic neuropeptide Y, plasma leptin and body weight gain and composition.

    PubMed

    Beck, Bernard; Burlet, Arlette; Max, Jean Pierre; Stricker-Krongrad, Alain

    The aim of this study was to determine the effects of the chronic ingestion of aspartame (ASP) on brain neuropeptide Y (NPY) concentrations, plasma hormones, food intake and body fat. Two groups of male Long-Evans rats, fed on a control (C) well-balanced diet, had to drink either a 0.1% ASP solution or water for a period of 14 weeks starting at weaning. Food intake and body weight were weekly recorded. At the end of the experiment, fat pads were sampled, leptin and insulin were measured in the plasma and NPY in several microdissected brain areas. Substituting ASP for water led to lower body weight (-8%; P<.004) and lower fat depot weight (-20%; P<.01) with no differences in energy intake or plasma insulin concentrations. Plasma leptin was significantly reduced by 34% (P<.05). Leptin concentrations were well-correlated with final body weight (r=.47; P<.025) and fat pad mass (r=.53; P<.01). NPY concentrations were 23% lower (P<.03) in the arcuate nucleus of ASP rats with no differences in other brain areas. The beneficial effects on body composition could be related to the decreased effects of NPY on lipid and energy metabolism, independently of insulin. The reasons for the NPY decrease (regulatory or toxicological) are not obvious. The constitutive amino acids of the ASP molecule might participate in the NPY regulation. PMID:11890951

  18. Effects of early and late neonatal bromocriptine treatment on hypothalamic neuropeptides, dopaminergic reward system and behavior of adult rats.

    PubMed

    Carvalho, Janaine C; Lisboa, Patricia C; de Oliveira, Elaine; Peixoto-Silva, Nayara; Pinheiro, Cintia R; Fraga, Mabel C; Claudio-Neto, Sylvio; Franci, Celso R; Manhães, Alex C; Moura, Egberto G

    2016-06-14

    In humans, bromocriptine (BRO) is used as a treatment for many disorders, such as prolactinomas, even during pregnancy and lactation. Previously we demonstrated that maternal BRO treatment at the end of lactation programs offspring for obesity and several endocrine dysfunctions. Here, we studied the long-term effects of direct BRO injection in neonatal Wistar rats on their dopaminergic pathway, anxiety-like behavior and locomotor activity at adulthood. Male pups were either s.c. injected with BRO (0.1μg/once daily) from postnatal day (PN) 1 to 10 or from PN11 to 20. Controls were injected with methanol-saline. Body mass, food intake, neuropeptides, dopamine pathway parameters, anxiety-like behavior and locomotor activity were analyzed. The dopamine pathway was analyzed in the ventral tegmental area (VTA), nucleus accumbens (NAc) and dorsal striatum (DS) at PN180. PN1-10 BRO-treated animals had normal body mass and adiposity but lower food intake and plasma prolactin (PRL). This group had higher POMC in the arcuate nucleus (ARC), higher tyrosine hydroxylase (TH) in the VTA, higher dopa decarboxylase (DDc), higher D2R and μu-opioid receptor in the NAc. Concerning behavior in elevated plus maze (EPM), BRO-treated animals displayed more anxiety-like behaviors. PN11-20 BRO-treated showed normal body mass and adiposity but higher food intake and plasma PRL. This group had lower POMC in the ARC, lower TH in the VTA and lower DAT in the NAc. BRO-treated animals showed less anxiety-like behaviors in the EPM. Thus, neonatal BRO injection, depending on the time of treatment, leads to different long-term dysfunctions in the dopaminergic reward system, food intake behavior and anxiety levels, findings that could be partially due to PRL and POMC changes. PMID:27038750

  19. Neuropeptides and diabetic retinopathy

    PubMed Central

    Gábriel, Robert

    2013-01-01

    Diabetic retinopathy, a common complication of diabetes, develops in 75% of patients with type 1 and 50% of patients with type 2 diabetes, progressing to legal blindness in about 5%. In the recent years, considerable efforts have been put into finding treatments for this condition. It has been discovered that peptidergic mechanisms (neuropeptides and their analogues, activating a diverse array of signal transduction pathways through their multiple receptors) are potentially important for consideration in drug development strategies. A considerable amount of knowledge has been accumulated over the last three decades on human retinal neuropeptides and those elements in the pathomechanisms of diabetic retinopathy which might be related to peptidergic signal transduction. Here, human retinal neuropeptides and their receptors are reviewed, along with the theories relevant to the pathogenesis of diabetic retinopathy both in humans and in experimental models. By collating this information, the curative potential of certain neupeptides and their analogues/antagonists can also be discussed, along with the existing clinical treatments of diabetic retinopathy. The most promising peptidergic pathways for which treatment strategies may be developed at present are stimulation of the somatostatin-related pathway and the pituitary adenylyl cyclase-activating polypeptide-related pathway or inhibition of angiotensinergic mechanisms. These approaches may result in the inhibition of vascular endothelial growth factor production and neuronal apoptosis; therefore, both the optical quality of the image and the processing capability of the neural circuit in the retina may be saved. PMID:23043302

  20. Arcuate Fractures in Olympus Mons Caldera

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site]

    This VIS image shows part of the caldera at the summit of Olympus Mons -- a huge volcano. The arcuate (curved) fractures seen on the right side of the caldera floor were likely formed when later eruptions occurred -- note the smoother, younger section to the left.

    Image information: VIS instrument. Latitude 18.2, Longitude 226.9 East (133.1 West). 19 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  1. NEUROENDOCRINE ACTIONS AND REGULATION OF HYPOTHALAMIC NEUROPEPTIDE Y DURING LACTATION

    PubMed Central

    Crowley, W,R.; Ramoz, G.; Torto, R.; Keefe, K.A.; Wang, J. J.; Kalra, S. P.

    2007-01-01

    The expression of neuropeptide Y (NPY) and its co-messenger, agouti-related peptide (AgRP), in arcuate neurons of the hypothalamus is increased during lactation in rats. Our research has been addressing the questions of the physiological actions of these peptides during lactation and the physiological signals associated with lactation that result in increased expression of their genes. Our studies indicate that NPY and AgRP exert pleiotropic actions during lactation that help integrate neuroendocrine regulation of energy balance with controls over anterior and posterior pituitary hormone secretion. Further, reciprocal signaling to the NPY/AgRP system by leptin and ghrelin is responsible for the changes in expression of these hypothalamic peptides in lactating animals, and thus, may contribute to regulation of food intake and the various neuroendocrine adaptations of lactation. PMID:17241697

  2. Renal Arcuate Vein Microthrombi-Associated AKI

    PubMed Central

    Redfern, Andrew; Mahmoud, Huda; McCulloch, Tom; Shardlow, Adam; Hall, Matthew; Byrne, Catherine

    2015-01-01

    Backgrounds and objectives This report describes six patients with AKI stages 2–3 (median admission creatinine level, 2.75 mg/dl [range, 1.58–5.44 mg/dl]), hematuria (five with hemoproteinuria), and unremarkable imaging with an unusual and unexplained histologic diagnosis on renal biopsy. Design, setting, participants, & measurements The patients were young adults who presented to two neighboring United Kingdom nephrology centers over a 40-month period (between July 2010 and November 2013). Four were male, and the median age was 22.5 years (range, 18–27 years). Their principal symptoms were flank pain or lower back pain. All had consumed alcohol in the days leading up to admission. Results Renal biopsy demonstrated microthrombi in the renal arcuate veins with a corresponding stereotypical, localized inflammatory infiltrate at the corticomedullary junction. All patients recovered to baseline renal function with supportive care (median, 17 days; range, 6–60 days), and none required RRT. To date, additional investigations have not revealed an underlying cause for these histopathologic changes. Investigations have included screening for thrombophilic tendencies, renal vein Doppler ultrasonographic studies, and testing for recreational drugs and alcohol (including liquid chromatography–mass spectrometry of urine) to look for so-called designer drugs. Inquiries to the United Kingdom National Poisons Information Centre have identified no other cases with similar presentation or histologic findings. Conclusions Increased awareness and additional study of future cases may lead to a greater understanding of the underlying pathophysiologic mechanisms that caused AKI in these patients. PMID:25452224

  3. The Physiological Role of Arcuate Kisspeptin Neurons in the Control of Reproductive Function in Female Rats

    PubMed Central

    Beale, K.E.; Kinsey-Jones, J.S.; Gardiner, J.V.; Harrison, E.K.; Thompson, E.L.; Hu, M.H.; Sleeth, M.L.; Sam, A.H.; Greenwood, H.C.; McGavigan, A.K.; Dhillo, W.S.; Mora, J.M.; Li, X.F.; Franks, S.; Bloom, S.R.; O'Byrne, K.T.

    2014-01-01

    Kisspeptin plays a pivotal role in pubertal onset and reproductive function. In rodents, kisspeptin perikarya are located in 2 major populations: the anteroventral periventricular nucleus and the hypothalamic arcuate nucleus (ARC). These nuclei are believed to play functionally distinct roles in the control of reproduction. The anteroventral periventricular nucleus population is thought to be critical in the generation of the LH surge. However, the physiological role played by the ARC kisspeptin neurons remains to be fully elucidated. We used bilateral stereotactic injection of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC of adult female rats to investigate the physiological role of kisspeptin neurons in this nucleus. Female rats with kisspeptin knockdown in the ARC displayed a significantly reduced number of both regular and complete oestrous cycles and significantly longer cycles over the 100-day period of the study. Further, kisspeptin knockdown in the ARC resulted in a decrease in LH pulse frequency. These data suggest that maintenance of ARC-kisspeptin levels is essential for normal pulsatile LH release and oestrous cyclicity. PMID:24424033

  4. Neuromedin U in the paraventricular and arcuate hypothalamic nuclei increases non-exercise activity thermogenesis.

    PubMed

    Novak, C M; Zhang, M; Levine, J A

    2006-08-01

    Brain neuromedin U (NMU) has been associated with the regulation of both energy intake and expenditure. We hypothesized that NMU induces changes in spontaneous physical activity and nonexercise activity thermogenesis (NEAT) through its actions on hypothalamic nuclei. We applied increasing doses of NMU directly to the paraventricular (PVN) and arcuate hypothalamic nuclei using chronic unilateral guide cannulae. In both nuclei, NMU significantly and dose-dependently increased physical activity and NEAT. Moreover, NMU increased physical activity and NEAT during the first hour of the dark phase, indicating that the reduction of sleep is unlikely to account for the increased physical activity seen with NMU treatment. As a positive control, we demonstrated that paraventricular NMU also significantly decreased food intake, as well as body weight. These data demonstrate that NMU is positively associated with NEAT through its actions in the PVN and arcuate nucleus. In co-ordination with its suppressive effects on feeding, the NEAT-activating effects of NMU make it a potential candidate in the combat of obesity. PMID:16867180

  5. Increase of Long-Term ‘Diabesity’ Risk, Hyperphagia, and Altered Hypothalamic Neuropeptide Expression in Neonatally Overnourished ‘Small-For-Gestational-Age’ (SGA) Rats

    PubMed Central

    Schellong, Karen; Neumann, Uta; Rancourt, Rebecca C.; Plagemann, Andreas

    2013-01-01

    Background Epidemiological data have shown long-term health adversity in low birth weight subjects, especially concerning the metabolic syndrome and ‘diabesity’ risk. Alterations in adult food intake have been suggested to be causally involved. Responsible mechanisms remain unclear. Methods and Findings By rearing in normal (NL) vs. small litters (SL), small-for-gestational-age (SGA) rats were neonatally exposed to either normal (SGA-in-NL) or over-feeding (SGA-in-SL), and followed up into late adult age as compared to normally reared appropriate-for-gestational-age control rats (AGA-in-NL). SGA-in-SL rats displayed rapid neonatal weight gain within one week after birth, while SGA-in-NL growth caught up only at juvenile age (day 60), as compared to AGA-in-NL controls. In adulthood, an increase in lipids, leptin, insulin, insulin/glucose-ratio (all p<0.05), and hyperphagia under normal chow as well as high-energy/high-fat diet, modelling modern ‘westernized’ lifestyle, were observed only in SGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (p<0.05). Lasercapture microdissection (LMD)-based neuropeptide expression analyses in single neuron pools of the arcuate hypothalamic nucleus (ARC) revealed a significant shift towards down-regulation of the anorexigenic melanocortinergic system (proopiomelanocortin, Pomc) in SGA-in-SL rats (p<0.05). Neuropeptide expression within the orexigenic system (neuropeptide Y (Npy), agouti-related-peptide (Agrp) and galanin (Gal)) was not significantly altered. In essence, the ‘orexigenic index’, proposed here as a neuroendocrine ‘net-indicator’, was increased in SGA-in-SL regarding Npy/Pomc expression (p<0.01), correlated to food intake (p<0.05). Conclusion Adult SGA rats developed increased ‘diabesity’ risk only if exposed to neonatal overfeeding. Hypothalamic malprogramming towards decreased anorexigenic activity was involved into the pathophysiology of this neonatally acquired adverse phenotype. Neonatal

  6. Neuropeptide GPCRs in C. elegans

    PubMed Central

    Frooninckx, Lotte; Van Rompay, Liesbeth; Temmerman, Liesbet; Van Sinay, Elien; Beets, Isabel; Janssen, Tom; Husson, Steven J.; Schoofs, Liliane

    2012-01-01

    Like most organisms, the nematode Caenorhabditis elegans relies heavily on neuropeptidergic signaling. This tiny animal represents a suitable model system to study neuropeptidergic signaling networks with single cell resolution due to the availability of powerful molecular and genetic tools. The availability of the worm’s complete genome sequence allows researchers to browse through it, uncovering putative neuropeptides and their cognate G protein-coupled receptors (GPCRs). Many predictions have been made about the number of C. elegans neuropeptide GPCRs. In this review, we report the state of the art of both verified as well as predicted C. elegans neuropeptide GPCRs. The predicted neuropeptide GPCRs are incorporated into the receptor classification system based on their resemblance to orthologous GPCRs in insects and vertebrates. Appointing the natural ligand(s) to each predicted neuropeptide GPCR (receptor deorphanization) is a crucial step during characterization. The development of deorphanization strategies resulted in a significant increase in the knowledge of neuropeptidergic signaling in C. elegans. Complementary localization and functional studies demonstrate that neuropeptides and their GPCRs represent a rich potential source of behavioral variability in C. elegans. Here, we review all neuropeptidergic signaling pathways that so far have been functionally characterized in C. elegans. PMID:23267347

  7. Sensory neuropeptides and airway function.

    PubMed

    Solway, J; Leff, A R

    1991-12-01

    Sensory nerves synthesize tachykinins and calcitonin-gene related peptide and package these neuropeptides together in synaptic vesicles. Stimulation of these C-fibers by a range of chemical and physical factors results in afferent neuronal conduction that elicits central parasympathetic reflexes and in antidromic conduction that results in local release of neuropeptides through the axon reflex. In the airways, sensory neuropeptides act on bronchial smooth muscle, the mucosal vasculature, and submucosal glands to promote airflow obstruction, hyperemia, microvascular hyperpermeability, and mucus hypersecretion. In addition, tachykinins potentiate cholinergic neurotransmission. Proinflammatory effects of these peptides also promote the recruitment, adherence, and activation of granulocytes that may further exacerbate neurogenic inflammation (i.e., neuropeptide-induced plasma extravasation and vasodilation). Enzymatic degradation limits the physiological effects of tachykinins but may be impaired by respiratory infection or other factors. Given their sensitivity to noxious compounds and physical stimuli and their potent effects on airway function, it is possible that neuropeptide-containing sensory nerves play an important role in mediating airway responses in human disease. Supporting this view are the striking phenomenological similarities between hyperpnea-induced bronchoconstriction (HIB) in guinea pigs and HIB in patients with exercise-induced asthma. Endogenous tachykinins released from airway sensory nerves mediate HIB in guinea pigs and also cause hyperpnea-induced bronchovascular hyperpermeability in these animals. On the basis of these observations, it is reasonable to speculate that sensory neuropeptides participate in the pathogenesis of hyperpnea-induced airflow obstruction in human asthmatic subjects as well. PMID:1663932

  8. The Role of the Arcuate Fasciculus in Conduction Aphasia

    ERIC Educational Resources Information Center

    Bernal, Byron; Ardila, Alfredo

    2009-01-01

    In aphasia literature, it has been considered that a speech repetition defect represents the main constituent of conduction aphasia. Conduction aphasia has frequently been interpreted as a language impairment due to lesions of the arcuate fasciculus (AF) that disconnect receptive language areas from expressive ones. Modern neuroradiological…

  9. Posterior Cortical Atrophy Presenting with Superior Arcuate Field Defect

    PubMed Central

    Wan, Sue Ling; Bukowska, Danuta M.; Ford, Stephen; Chen, Fred K.

    2015-01-01

    An 80-year-old female with reading difficulty presented with progressive arcuate field defect despite low intraocular pressure. Over a 5-year period, the field defect evolved into an incongruous homonymous hemianopia and the repeated neuroimaging revealed progressive posterior cortical atrophy. Further neuropsychiatric assessment demonstrated symptoms and signs consistent with Benson's syndrome. PMID:26417467

  10. Mesolimbic neuropeptide W coordinates stress responses under novel environments.

    PubMed

    Motoike, Toshiyuki; Long, Jeffrey M; Tanaka, Hirokazu; Sinton, Christopher M; Skach, Amber; Williams, S Clay; Hammer, Robert E; Sakurai, Takeshi; Yanagisawa, Masashi

    2016-05-24

    Neuropeptide B (NPB) and neuropeptide W (NPW) are endogenous neuropeptide ligands for the G protein-coupled receptors NPBWR1 and NPBWR2. Here we report that the majority of NPW neurons in the mesolimbic region possess tyrosine hydroxylase immunoreactivity, indicating that a small subset of dopaminergic neurons coexpress NPW. These NPW-containing neurons densely and exclusively innervate two limbic system nuclei in adult mouse brain: the lateral bed nucleus of the stria terminalis and the lateral part of the central amygdala nucleus (CeAL). In the CeAL of wild-type mice, restraint stress resulted in an inhibition of cellular activity, but this stress-induced inhibition was attenuated in the CeAL neurons of NPW(-/-) mice. Moreover, the response of NPW(-/-) mice to either formalin-induced pain stimuli or a live rat (i.e., a potential predator) was abnormal only when they were placed in a novel environment: The mice failed to show the normal species-specific self-protective and aversive reactions. In contrast, the behavior of NPW(-/-) mice in a habituated environment was indistinguishable from that of wild-type mice. These results indicate that the NPW/NPBWR1 system could play a critical role in the gating of stressful stimuli during exposure to novel environments. PMID:27140610

  11. ASICs and neuropeptides.

    PubMed

    Vick, Jonathan S; Askwith, Candice C

    2015-07-01

    The acid sensing ion channels (ASICs) are proton-gated cation channels expressed throughout the nervous system. ASICs are activated during acidic pH fluctuations, and recent work suggests that they are involved in excitatory synaptic transmission. ASICs can also induce neuronal degeneration and death during pathological extracellular acidosis caused by ischemia, autoimmune inflammation, and traumatic injury. Many endogenous neuromodulators target ASICs to affect their biophysical characteristics and contributions to neuronal activity. One of the most unconventional types of modulation occurs with the interaction of ASICs and neuropeptides. Collectively, FMRFamide-related peptides and dynorphins potentiate ASIC activity by decreasing the proton-sensitivity of steady state desensitization independent of G protein-coupled receptor activation. By decreasing the proton-sensitivity of steady state desensitization, the FMRFamide-related peptides and dynorphins permit ASICs to remain active at more acidic basal pH. Unlike the dynorphins, some FMRFamide-related peptides also potentiate ASIC activity by slowing inactivation and increasing the sustained current. Through mechanistic studies, the modulation of ASICs by FMRFamide-related peptides and dynorphins appears to be through distinct interactions with the extracellular domain of ASICs. Dynorphins are expressed throughout the nervous system and can increase neuronal death during prolonged extracellular acidosis, suggesting that the interaction between dynorphins and ASICs may have important consequences for the prevention of neurological injury. The overlap in expression of FMRFamide-related peptides with ASICs in the dorsal horn of the spinal cord suggests that their interaction may have important consequences for the treatment of pain during injury and inflammation. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'. PMID:25592215

  12. ASICS AND NEUROPEPTIDES

    PubMed Central

    Vick, Jonathan S.; Askwith, Candice C.

    2015-01-01

    The acid sensing ion channels (ASICs) are proton-gated cation channels expressed throughout the nervous system. ASICs are activated during acidic pH fluctuations, and recent work suggests that they are involved in excitatory synaptic transmission. ASICs can also induce neuronal degeneration and death during pathological extracellular acidosis caused by ischemia, autoimmune inflammation, and traumatic injury. Many endogenous neuromodulators target ASICs to affect their biophysical characteristics and contributions to neuronal activity. One of the most unconventional types of modulation occurs with the interaction of ASICs and neuropeptides. Collectively, FMRFamide-related peptides and dynorphins potentiate ASIC activity by decreasing the proton-sensitivity of steady state desensitization independent of G protein-coupled receptor activation. By decreasing the proton-sensitivity of steady state desensitization, the FMRFamide-related peptides and dynorphins permit ASICs to remain active at more acidic basal pH. Unlike the dynorphins, some FMRFamide-related peptides also potentiate ASIC activity by slowing inactivation and increasing the sustained current. Through mechanistic studies, the modulation of ASICs by FMRFamide-related peptides and dynorphins appears to be through distinct interactions with the extracellular domain of ASICs. Dynorphins are expressed throughout the nervous system and can increase neuronal death during prolonged extracellular acidosis, suggesting that the interaction between dynorphins and ASICs may have important consequences for the prevention of neurological injury. The overlap in expression of FMRFamide-related peptides with ASICs in the dorsal horn of the spinal cord suggests that their interaction may have important consequences for the treatment of pain during injury and inflammation. PMID:25592215

  13. Brain clock driven by neuropeptides and second messengers.

    PubMed

    Miro-Bueno, Jesus; Sosík, Petr

    2014-09-01

    The master circadian pacemaker in mammals is localized in a small portion of the brain called the suprachiasmatic nucleus (SCN). It is unclear how the SCN produces circadian rhythms. A common interpretation is that the SCN produces oscillations through the coupling of genetic oscillators in the neurons. The coupling is effected by a network of neuropeptides and second messengers. This network is crucial for the correct function of the SCN. However, models that study a possible oscillatory behavior of the network itself have received little attention. Here we propose and analyze a model to examine this oscillatory potential. We show that an intercellular oscillator emerges in the SCN as a result of the neuropeptide and second messenger dynamics. We find that this intercellular clock can produce circadian rhythms by itself with and without genetic clocks. We also found that the model is robust to perturbation of parameters and can be entrained by light-dark cycles. PMID:25314471

  14. Brain clock driven by neuropeptides and second messengers

    NASA Astrophysics Data System (ADS)

    Miro-Bueno, Jesus; Sosík, Petr

    2014-09-01

    The master circadian pacemaker in mammals is localized in a small portion of the brain called the suprachiasmatic nucleus (SCN). It is unclear how the SCN produces circadian rhythms. A common interpretation is that the SCN produces oscillations through the coupling of genetic oscillators in the neurons. The coupling is effected by a network of neuropeptides and second messengers. This network is crucial for the correct function of the SCN. However, models that study a possible oscillatory behavior of the network itself have received little attention. Here we propose and analyze a model to examine this oscillatory potential. We show that an intercellular oscillator emerges in the SCN as a result of the neuropeptide and second messenger dynamics. We find that this intercellular clock can produce circadian rhythms by itself with and without genetic clocks. We also found that the model is robust to perturbation of parameters and can be entrained by light-dark cycles.

  15. Hypothalamic neuropeptide signaling in alcohol addiction.

    PubMed

    Barson, Jessica R; Leibowitz, Sarah F

    2016-02-01

    The hypothalamus is now known to regulate alcohol intake in addition to its established role in food intake, in part through neuromodulatory neurochemicals termed neuropeptides. Certain orexigenic neuropeptides act in the hypothalamus to promote alcohol drinking, although they affect different aspects of the drinking response. These neuropeptides, which include galanin, the endogenous opioid enkephalin, and orexin/hypocretin, appear to stimulate alcohol intake not only through mechanisms that promote food intake but also by enhancing reward and reinforcement from alcohol. Moreover, these neuropeptides participate in a positive feedback relationship with alcohol, whereby they are upregulated by alcohol intake to promote even further consumption. They contrast with other orexigenic neuropeptides, such as melanin-concentrating hormone and neuropeptide Y, which promote alcohol intake under limited circumstances, are not consistently stimulated by alcohol, and do not enhance reward. They also contrast with neuropeptides that can be anorexigenic, including the endogenous opioid dynorphin, corticotropin-releasing factor, and melanocortins, which act in the hypothalamus to inhibit alcohol drinking as well as reward and therefore counter the ingestive drive promoted by orexigenic neuropeptides. Thus, while multiple hypothalamic neuropeptides may work together to regulate different aspects of the alcohol drinking response, excessive signaling from orexigenic neuropeptides or inadequate signaling from anorexigenic neuropeptides can therefore allow alcohol drinking to become dysregulated. PMID:25689818

  16. Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice.

    PubMed

    Gotthardt, Juliet D; Verpeut, Jessica L; Yeomans, Bryn L; Yang, Jennifer A; Yasrebi, Ali; Roepke, Troy A; Bello, Nicholas T

    2016-02-01

    Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%-52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%-13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%-42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%-60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%-32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%-75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy. PMID:26653760

  17. Leptin stimulates neuropeptide Y and cocaine amphetamine-regulated transcript coexpressing neuronal activity in the dorsomedial hypothalamus in diet-induced obese mice.

    PubMed

    Lee, Shin J; Verma, Saurabh; Simonds, Stephanie E; Kirigiti, Melissa A; Kievit, Paul; Lindsley, Sarah R; Loche, Alberto; Smith, M Susan; Cowley, Michael A; Grove, Kevin L

    2013-09-18

    Neuropeptide Y (NPY) neurons in both the arcuate nucleus of the hypothalamus (ARH) and the dorsomedial hypothalamus (DMH) have been implicated in food intake and obesity. However, while ARH NPY is highly expressed in the lean animal, DMH NPY mRNA expression is observed only after diet-induced obesity (DIO). Furthermore, while ARH NPY neurons are inhibited by leptin, the effect of this adipokine on DMH NPY neurons is unknown. In this study we show that in contrast to the consistent expression in the ARH, DMH NPY mRNA expression was undetectable until after 10 weeks in mice fed a high-fat diet, and peaked at 20 weeks. Surprisingly, electrophysiological experiments demonstrated that leptin directly depolarized and increased the firing rate of DMH NPY neurons in DIO mice. To further differentiate the regulation of DMH and ARH NPY populations, fasting decreased expression of DMH NPY expression, while it increased ARH NPY expression. However, treatment with a leptin receptor antagonist failed to alter DMH NPY expression, indicating that leptin may not be the critical factor regulating mRNA expression. Importantly, we also demonstrated that DMH NPY neurons coexpress cocaine amphetamine-regulated transcript (CART); however, CART mRNA expression in the DMH peaked earlier in the progression of DIO. This study demonstrates novel and important findings. First, NPY and CART are coexpressed in the same neurons within the DMH, and second, leptin stimulates DMH NPY neurons. These studies suggest that during the progression of DIO, there is an unknown signal that drives the expression of the orexigenic NPY signal within the DMH, and that the chronic hyperleptinemia increases the activity of these NPY/CART neurons. PMID:24048859

  18. Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons

    PubMed Central

    Adori, Csaba; Barde, Swapnali; Bogdanovic, Nenad; Uhlén, Mathias; Reinscheid, Rainer R.; Kovacs, Gabor G.; Hökfelt, Tomas

    2015-01-01

    Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects. In rodents, NPS is expressed in a few pontine cell clusters. Its receptor (NPSR1) is, however, widely distributed in the brain. The anxiolytic and arousal-promoting effects of NPS make the NPS–NPSR1 system an interesting potential drug target in mood-related disorders. However, so far possible disease-related mechanisms involving NPS have only been studied in rodents. To validate the relevance of these animal studies for i.a. drug development, we have explored the distribution of NPS-expressing neurons in the human pons using in situ hybridization and stereological methods and we compared the distribution of NPS mRNA expressing neurons in the human and rat brain. The calculation revealed a total number of 22,317 ± 2411 NPS mRNA-positive neurons in human, bilaterally. The majority of cells (84%) were located in the parabrachial area in human: in the extension of the medial and lateral parabrachial nuclei, in the Kölliker-Fuse nucleus and around the adjacent lateral lemniscus. In human, in sharp contrast to the rodents, only very few NPS-positive cells (5%) were found close to the locus coeruleus. In addition, we identified a smaller cell cluster (11% of all NPS cells) in the pontine central gray matter both in human and rat, which has not been described previously even in rodents. We also examined the distribution of NPSR1 mRNA-expressing neurons in the human pons. These cells were mainly located in the rostral laterodorsal tegmental nucleus, the cuneiform nucleus, the microcellular tegmental nucleus region and in the periaqueductal gray. Our results show that both NPS and NPSR1 in the human pons are preferentially localized in regions of importance for integration of visceral autonomic information and emotional behavior. The reported interspecies differences must, however, be considered when looking for targets for new pharmacotherapeutical interventions. PMID:26441556

  19. Median arcuate ligament syndrome: a nonvascular, vascular diagnosis.

    PubMed

    Skeik, Nedaa; Cooper, Leslie T; Duncan, Audra A; Jabr, Fadi I

    2011-07-01

    Median arcuate ligament syndrome (MALS) is often diagnosed when idiopathic, episodic abdominal pain is associated with dynamic compression of the proximal celiac artery by fibers of the median arcuate ligament. The character of the abdominal pain is often postprandial and associated with gradual weight loss from poor food intake, suggestive of chronic mesenteric ischemia. However, the pathognomonic imaging feature of dynamic, ostial celiac artery compression with expiration does not consistently predict clinical improvement from revascularization. Proposed but unproven pathophysiological mechanisms include neurogenic pain from compression of the splanchnic nerve plexus and intermittent ischemia from compression of the celiac artery. Alterations in blood flow and ganglion compression are both associated with delayed gastric emptying, another physiological correlate of the clinical syndrome. Published reports describe a variable response to revascularization and nerve plexus resection suggest a need for translational research to better characterize this poorly understood clinical entity. We illustrate the current gaps in our knowledge of MALS with the case of a 51-year-old woman with a 4-year history of chronic abdominal pain who responded to a combination of ganglion resection and celiac artery reconstruction. PMID:21536596

  20. Regulation of arcuate genes by developmental exposures to endocrine-disrupting compounds in female rats.

    PubMed

    Roepke, Troy A; Yang, Jennifer A; Yasrebi, Ali; Mamounis, Kyle J; Oruc, Elif; Zama, Aparna Mahakali; Uzumcu, Mehmet

    2016-07-01

    Developmental exposure to endocrine-disrupting compounds (EDCs) alters reproduction and energy homeostasis, both of which are regulated by the arcuate nucleus (ARC). Little is known about the effects of EDC on ARC gene expression. In Experiment #1, pregnant dams were treated with either two doses of bisphenol A (BPA) or oil from embryonic day (E)18-21. Neonates were injected from postnatal day (PND)0-7. Vaginal opening, body weights, and ARC gene expression were measured. Chrm3 (muscarinic receptor 3) and Adipor1 (adiponectin receptor 1) were decreased by BPA. Bdnf (brain-derived neurotropic factor), Igf1 (insulin-like growth factor 1), Htr2c (5-hydroxytryptamine receptor), and Cck2r (cholescystokinin 2 receptor) were impacted. In Experiment #2, females were exposed to BPA, diethylstilbestrol (DES), di(2-ethylhexyl)phthalate, or methoxychlor (MXC) during E11-PND7. MXC and DES advanced the age of vaginal opening and ARC gene expression was impacted. These data indicate that EDCs alter ARC genes involved in reproduction and energy homeostasis in females. PMID:27103539

  1. The hypothalamic neuropeptide FF network is impaired in hypertensive patients

    PubMed Central

    Goncharuk, Valeri D; Buijs, Ruud M; Jhamandas, Jack H; Swaab, Dick F

    2014-01-01

    Background The human hypothalamus contains the neuropeptide FF (NPFF) neurochemical network. Animal experiments demonstrated that NPFF is implicated in the central cardiovascular regulation. We therefore studied expression of this peptide in the hypothalamus of individuals who suffered from essential hypertension (n = 8) and died suddenly due to acute myocardial infarction (AMI), and compared to that of healthy individuals (controls) (n = 6) who died abruptly due to mechanical trauma of the chest. Methods The frozen right part of the hypothalamus was cut coronally into serial sections of 20 μm thickness, and each tenth section was stained immunohistochemically using antibody against NPFF. The central section through each hypothalamic nucleus was characterized by the highest intensity of NPFF immunostaining and thus was chosen for quantitative densitometry. Results In hypertensive patients, the area occupied by NPFF immunostained neuronal elements in the central sections through the suprachiasmatic nucleus (SCh), paraventricular hypothalamic nucleus (Pa), bed nucleus of the stria terminalis (BST), perinuclear zone (PNZ) of the supraoptic nucleus (SON), dorso- (DMH), ventromedial (VMH) nuclei, and perifornical nucleus (PeF) was dramatically decreased compared to controls, ranging about six times less in the VMH to 15 times less in the central part of the BST (BSTC). The NPFF innervation of both nonstained neuronal profiles and microvasculature was extremely poor in hypertensive patients compared to control. Conclusions The decreased NPFF expression in the hypothalamus of hypertensive patients might be a cause of impairment of its interaction with other neurochemical systems, and thereby might be involved in the pathogenesis of the disease. PMID:25161813

  2. Embolization in a Patient with Ruptured Anterior Inferior Pancreaticoduodenal Arterial Aneurysm with Median Arcuate Ligament Syndrome

    SciTech Connect

    Ogino, Hiroyuki; Sato, Yozo; Banno, Tatsuo; Arakawa, Toshinao; Hara, Masaki

    2002-08-15

    In median arcuate ligament syndrome, the root of the celiac artery is compressed and narrowed by the median arcuate ligament of the diaphragm during expiration, causing abdominal angina.Aneurysm may be formed in arteries of the pancreas and duodenum due toa chronic increase in blood flow from the superior mesenteric artery into the celiac arterial region. We report a patient saved by embolization with coils of ruptured aneurysm that developed with markedly dilated anterior inferior pancreaticoduodenal artery due to median arcuate ligament syndrome.

  3. Exercise-related transient abdominal pain secondary to median arcuate ligament syndrome: a case report.

    PubMed

    Haskins, Ivy N; Harr, Jeffrey N; Brody, Fred

    2016-07-01

    Exercise-related transient abdominal pain is a common entity in young athletes. An uncommon aetiology of this type of pain is median arcuate ligament syndrome. This article details an 18-year-old field hockey player who presented with a 1-year history of exercise-related transient abdominal pain. Despite a trial of preventative strategies, the patient's pain persisted, prompting surgical intervention. Following a laparoscopic median arcuate ligament release, the patient's symptoms resolved. Therefore, when exercise-related transient abdominal pain persists despite precautionary measures, median arcuate ligament syndrome should be considered. PMID:26542078

  4. Neuropeptide receptor transcriptome reveals unidentified neuroendocrine pathways.

    PubMed

    Yamanaka, Naoki; Yamamoto, Sachie; Zitnan, Dusan; Watanabe, Ken; Kawada, Tsuyoshi; Satake, Honoo; Kaneko, Yu; Hiruma, Kiyoshi; Tanaka, Yoshiaki; Shinoda, Tetsuro; Kataoka, Hiroshi

    2008-01-01

    Neuropeptides are an important class of molecules involved in diverse aspects of metazoan development and homeostasis. Insects are ideal model systems to investigate neuropeptide functions, and the major focus of insect neuropeptide research in the last decade has been on the identification of their receptors. Despite these vigorous efforts, receptors for some key neuropeptides in insect development such as prothoracicotropic hormone, eclosion hormone and allatotropin (AT), remain undefined. In this paper, we report the comprehensive cloning of neuropeptide G protein-coupled receptors from the silkworm, Bombyx mori, and systematic analyses of their expression. Based on the expression patterns of orphan receptors, we identified the long-sought receptor for AT, which is thought to stimulate juvenile hormone biosynthesis in the corpora allata (CA). Surprisingly, however, the AT receptor was not highly expressed in the CA, but instead was predominantly transcribed in the corpora cardiaca (CC), an organ adjacent to the CA. Indeed, by using a reverse-physiological approach, we purified and characterized novel allatoregulatory peptides produced in AT receptor-expressing CC cells, which may indirectly mediate AT activity on the CA. All of the above findings confirm the effectiveness of a systematic analysis of the receptor transcriptome, not only in characterizing orphan receptors, but also in identifying novel players and hidden mechanisms in important biological processes. This work illustrates how using a combinatorial approach employing bioinformatic, molecular, biochemical and physiological methods can help solve recalcitrant problems in neuropeptide research. PMID:18725956

  5. An unusual case of left renal artery compression: a rare type of median arcuate ligament syndrome.

    PubMed

    Arazińska, Agata; Polguj, Michał; Wojciechowski, Andrzej; Trębiński, Łukasz; Stefańczyk, Ludomir

    2016-04-01

    Compression from median arcuate ligament was observed during multidetector 64-row computed tomography in a Caucasian 30-year-old female. The patient was referred for examination to exclude anatomical pathologies causing hypertension. The examination demonstrated that left renal artery, which had its origin in the chest (at the level of upper one-third of Th12), was compressed as it passed by median arcuate ligament of the diaphragm. In addition, aortic compression and kinked shape was also revealed. PMID:25940812

  6. Neuropeptide evolution: Chelicerate neurohormone and neuropeptide genes may reflect one or more whole genome duplications.

    PubMed

    Veenstra, Jan A

    2016-04-01

    Four genomes and two transcriptomes from six Chelicerate species were analyzed for the presence of neuropeptide and neurohormone precursors and their GPCRs. The genome from the spider Stegodyphus mimosarum yielded 87 neuropeptide precursors and 120 neuropeptide GPCRs. Many neuropeptide transcripts were also found in the transcriptomes of three other spiders, Latrodectus hesperus, Parasteatoda tepidariorum and Acanthoscurria geniculata. For the scorpion Mesobuthus martensii the numbers are 79 and 93 respectively. The very small genome of the house dust mite, Dermatophagoides farinae, on the other hand contains a much smaller number of such genes. A few new putative Arthropod neuropeptide genes were discovered. Thus, both spiders and the scorpion have an achatin gene and in spiders there are two different genes encoding myosuppressin-like peptides while spiders also have two genes encoding novel LGamides. Another finding is the presence of trissin in spiders and scorpions, while neuropeptide genes that seem to be orthologs of Lottia LFRYamide and Platynereis CCRFamide were also found. Such genes were also found in various insect species, but seem to be lacking from the Holometabola. The Chelicerate neuropeptide and neuropeptide GPCR genes often have paralogs. As the large majority of these are probably not due to local gene duplications, is plausible that they reflect the effects of one or more ancient whole genome duplications. PMID:26928473

  7. Reading impairment in a patient with missing arcuate fasciculus

    PubMed Central

    Rauschecker, Andreas M.; Deutsch, Gayle K.; Ben-Shachar, Michal; Schwartzman, Armin; Perry, Lee M.; Dougherty, Robert F.

    2009-01-01

    We describe the case of a child (“S”) who was treated with radiation therapy at age 5 for a recurrent malignant brain tumor. Radiation successfully abolished the tumor but caused radiation-induced tissue necrosis, primarily affecting cerebral white matter. S was introduced to us at age 15 because of her profound dyslexia. We assessed cognitive abilities and performed diffusion tensor imaging (DTI) to measure cerebral white matter pathways. Diffuse white matter differences were evident in T1-weighted, T2-weighted, diffusion anisotropy, and mean diffusivity measures in S compared to a group of 28 normal female controls. In addition, we found specific white matter pathway deficits by comparing tensor orientation directions in S’s brain with those of the control brains. While her principal diffusion direction maps appeared consistent with those of controls over most of the brain, there were tensor orientation abnormalities in the fiber tracts that form the superior longitudinal fasciculus (SLF) in both hemispheres. Tractography analysis indicated that the left and right arcuate fasciculus (AF), as well as other tracts within the SLF, were missing in S. Other major white matter tracts, such as the corticospinal and inferior occipitofrontal pathways, were intact. Functional MRI measurements indicated left-hemisphere dominanance for language with a normal activation pattern. Despite the left AF abnormality, S had preserved oral language with average sentence repetition skills. In addition to profound dyslexia, S exhibited visuospatial, calculation, and rapid naming deficits and was impaired in both auditory and spatial working memory. We propose that the reading and visuospatial deficits were due to the abnormal left and right SLF pathways, respectively. These results advance our understanding of the functional significance of the SLF and are the first to link radiation necrosis with selective damage to a specific set of fiber tracts. PMID:18775735

  8. Neuropeptide action in insects and crustaceans.

    PubMed

    Mykles, Donald L; Adams, Michael E; Gäde, Gerd; Lange, Angela B; Marco, Heather G; Orchard, Ian

    2010-01-01

    Physiological processes are regulated by a diverse array of neuropeptides that coordinate organ systems. The neuropeptides, many of which act through G protein-coupled receptors, affect the levels of cyclic nucleotides (cAMP and cGMP) and Ca(2+) in target tissues. In this perspective, their roles in molting, osmoregulation, metabolite utilization, and cardiovascular function are highlighted. In decapod crustaceans, inhibitory neuropeptides (molt-inhibiting hormone and crustacean hyperglycemic hormone) suppress the molting gland through cAMP- and cGMP-mediated signaling. In insects, the complex movements during ecdysis are controlled by ecdysis-triggering hormone and a cascade of downstream neuropeptides. Adipokinetic/hypertrehalosemic/hyperprolinemic hormones mobilize energy stores in response to increased locomotory activity. Crustacean cardioacceleratory (cardioactive) peptide, proctolin, and FMRFamide-related peptides act on the heart, accessory pulsatile organs, and excurrent ostia to control hemolymph distribution to tissues. The osmoregulatory challenge of blood gorging in Rhodnius prolixus requires the coordinated release of serotonin and diuretic and antidiuretic hormones acting on the midgut and Malpighian tubules. These studies illustrate how multiple neuropeptides allow for flexibility in response to physiological challenges. PMID:20550437

  9. Neuropeptide Y: A stressful review

    PubMed Central

    Reichmann, Florian; Holzer, Peter

    2016-01-01

    Stress is defined as an adverse condition that disturbs the homeostasis of the body and activates adaptation responses. Among the many pathways and mediators involved, neuropeptide Y (NPY) stands out due to its unique stress-relieving, anxiolytic and neuroprotective properties. Stress exposure alters the biosynthesis of NPY in distinct brain regions, the magnitude and direction of this effect varying with the duration and type of stress. NPY is expressed in particular neurons of the brainstem, hypothalamus and limbic system, which explains why NPY has an impact on stress-related changes in emotional-affective behaviour and feeding as well as on stress coping. The biological actions of NPY in mammals are mediated by the Y1, Y2, Y4 and Y5 receptor, Y1 receptor stimulation being anxiolytic whereas Y2 receptor activation is anxiogenic. Emerging evidence attributes NPY a role in stress resilience, the ability to cope with stress. Thus there is a negative correlation between stress-induced behavioural disruption and cerebral NPY expression in animal models of post-traumatic stress disorder. Exogenous NPY prevents the negative consequences of stress, and polymorphisms of the NPY gene are predictive of impaired stress processing and increased risk of neuropsychiatric diseases. Stress is also a factor contributing to, and resulting from, neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s disease, in which NPY appears to play an important neuroprotective role. This review summarizes the evidence for an implication of NPY in stress-related and neurodegenerative pathologies and addresses the cerebral NPY system as a therapeutic target. PMID:26441327

  10. Anatomical Variant of Atlas : Arcuate Foramen, Occpitalization of Atlas, and Defect of Posterior Arch of Atlas

    PubMed Central

    2015-01-01

    Objective We sought to examine anatomic variations of the atlas and the clinical significance of these variations. Methods We retrospectively reviewed 1029 cervical 3-dimensional (3D) CT images. Cervical 3D CT was performed between November 2011 and August 2014. Arcuate foramina were classified as partial or complete and left and/or right. Occipitalization of the atlas was classified in accordance with criteria specified by Mudaliar et al. Posterior arch defects of the atlas were classified in accordance with criteria specified by Currarino et al. Results One hundred and eight vertebrae (108/1029, 10.5%) showed an arcuate foramen. Bilateral arcuate foramina were present in 41 of these vertebrae and the remaining 67 arcuate foramina were unilateral (right 31, left 36). Right-side arcuate foramina were partial on 18 sides and complete on 54 sides. Left-side arcuate foramina were partial on 24 sides and complete on 53 sides. One case of atlas assimilation was found. Twelve patients (12/1029, 1.17%) had a defect of the atlantal posterior arch. Nine of these patients (9/1029, 0.87%) had a type A posterior arch defect. We also identified one type B, one type D, and one type E defect. Conclusion Preoperative diagnosis of occipitalization of the atlas and arcuate foramina using 3D CT is of paramount importance in avoiding neurovascular injury during surgery. It is important to be aware of posterior arch defects of the atlas because they may be misdiagnosed as a fracture. PMID:26819687

  11. Reduced Volume of the Arcuate Fasciculus in Adults with High-Functioning Autism Spectrum Conditions

    PubMed Central

    Moseley, Rachel L.; Correia, Marta M.; Baron-Cohen, Simon; Shtyrov, Yury; Pulvermüller, Friedemann; Mohr, Bettina

    2016-01-01

    Atypical language is a fundamental feature of autism spectrum conditions (ASC), but few studies have examined the structural integrity of the arcuate fasciculus, the major white matter tract connecting frontal and temporal language regions, which is usually implicated as the main transfer route used in processing linguistic information by the brain. Abnormalities in the arcuate have been reported in young children with ASC, mostly in low-functioning or non-verbal individuals, but little is known regarding the structural properties of the arcuate in adults with ASC or, in particular, in individuals with ASC who have intact language, such as those with high-functioning autism or Asperger syndrome. We used probabilistic tractography of diffusion-weighted imaging to isolate and scrutinize the arcuate in a mixed-gender sample of 18 high-functioning adults with ASC (17 Asperger syndrome) and 14 age- and IQ-matched typically developing controls. Arcuate volume was significantly reduced bilaterally with clearest differences in the right hemisphere. This finding remained significant in an analysis of all male participants alone. Volumetric reduction in the arcuate was significantly correlated with the severity of autistic symptoms as measured by the Autism-Spectrum Quotient. These data reveal that structural differences are present even in high-functioning adults with ASC, who presented with no clinically manifest language deficits and had no reported developmental language delay. Arcuate structural integrity may be useful as an index of ASC severity and thus as a predictor and biomarker for ASC. Implications for future research are discussed. PMID:27242478

  12. Reduced Volume of the Arcuate Fasciculus in Adults with High-Functioning Autism Spectrum Conditions.

    PubMed

    Moseley, Rachel L; Correia, Marta M; Baron-Cohen, Simon; Shtyrov, Yury; Pulvermüller, Friedemann; Mohr, Bettina

    2016-01-01

    Atypical language is a fundamental feature of autism spectrum conditions (ASC), but few studies have examined the structural integrity of the arcuate fasciculus, the major white matter tract connecting frontal and temporal language regions, which is usually implicated as the main transfer route used in processing linguistic information by the brain. Abnormalities in the arcuate have been reported in young children with ASC, mostly in low-functioning or non-verbal individuals, but little is known regarding the structural properties of the arcuate in adults with ASC or, in particular, in individuals with ASC who have intact language, such as those with high-functioning autism or Asperger syndrome. We used probabilistic tractography of diffusion-weighted imaging to isolate and scrutinize the arcuate in a mixed-gender sample of 18 high-functioning adults with ASC (17 Asperger syndrome) and 14 age- and IQ-matched typically developing controls. Arcuate volume was significantly reduced bilaterally with clearest differences in the right hemisphere. This finding remained significant in an analysis of all male participants alone. Volumetric reduction in the arcuate was significantly correlated with the severity of autistic symptoms as measured by the Autism-Spectrum Quotient. These data reveal that structural differences are present even in high-functioning adults with ASC, who presented with no clinically manifest language deficits and had no reported developmental language delay. Arcuate structural integrity may be useful as an index of ASC severity and thus as a predictor and biomarker for ASC. Implications for future research are discussed. PMID:27242478

  13. Neuropeptidomics: Mass Spectrometry-Based Identification and Quantitation of Neuropeptides

    PubMed Central

    2016-01-01

    Neuropeptides produced from prohormones by selective action of endopeptidases are vital signaling molecules, playing a critical role in a variety of physiological processes, such as addiction, depression, pain, and circadian rhythms. Neuropeptides bind to post-synaptic receptors and elicit cellular effects like classical neurotransmitters. While each neuropeptide could have its own biological function, mass spectrometry (MS) allows for the identification of the precise molecular forms of each peptide without a priori knowledge of the peptide identity and for the quantitation of neuropeptides in different conditions of the samples. MS-based neuropeptidomics approaches have been applied to various animal models and conditions to characterize and quantify novel neuropeptides, as well as known neuropeptides, advancing our understanding of nervous system function over the past decade. Here, we will present an overview of neuropeptides and MS-based neuropeptidomic strategies for the identification and quantitation of neuropeptides. PMID:27103886

  14. Neuropeptidomics: Mass Spectrometry-Based Identification and Quantitation of Neuropeptides.

    PubMed

    Lee, Ji Eun

    2016-03-01

    Neuropeptides produced from prohormones by selective action of endopeptidases are vital signaling molecules, playing a critical role in a variety of physiological processes, such as addiction, depression, pain, and circadian rhythms. Neuropeptides bind to post-synaptic receptors and elicit cellular effects like classical neurotransmitters. While each neuropeptide could have its own biological function, mass spectrometry (MS) allows for the identification of the precise molecular forms of each peptide without a priori knowledge of the peptide identity and for the quantitation of neuropeptides in different conditions of the samples. MS-based neuropeptidomics approaches have been applied to various animal models and conditions to characterize and quantify novel neuropeptides, as well as known neuropeptides, advancing our understanding of nervous system function over the past decade. Here, we will present an overview of neuropeptides and MS-based neuropeptidomic strategies for the identification and quantitation of neuropeptides. PMID:27103886

  15. Renovascular effects of neuropeptide-Y in the split hydronephrotic rat kidney: non-uniform pattern of vascular reactivity.

    PubMed Central

    Dietrich, M S; Fretschner, M; Nobiling, R; Persson, P B; Steinhausen, M

    1991-01-01

    1. The renovascular effects of neuropeptide-Y (NPY) were examined in the split hydronephrotic rat kidney. 2. Systemic infusion of low non-pressor doses of NPY (0.2 micrograms kg-1 up to 5.0 micrograms kg-1) produced a non-uniform pattern of vascular reactivity. In general, a significant constriction of the proximal and distal arcuate artery was seen at all doses. No constriction was seen at the interlobular artery or the larger part of the afferent arteriole. These segments initially dilated during the lower dose infusions. The very distal part of the afferent arteriole adjacent to the glomerulus and the proximal efferent arteriole responded in a similar way to the arcuate arteries. 3. NPY, locally applied into the tissue bath at concentrations of 1 nmol l-1 up to 25 nmol l-1, produced non-uniform vascular reactions similar to those of intravenously infused NPY. At the considerably higher local dosage of 1.14 mumol l-1, all vascular segments revealed vasoconstriction. 4. NPY application did not attenuate effects of acetylcholine. This observation suggests that the mechanism of NPY-induced vasoconstriction does not rely upon antagonism of endothelium-derived vasodilatation. 5. The pattern of vascular reactivity to NPY was substantially different from that known for the vasoconstrictors noradrenaline and angiotensin II in our preparation. PMID:1822552

  16. Mapping of Kisspeptin Receptor mRNA in the Whole Rat Brain and its Co-Localisation with Oxytocin in the Paraventricular Nucleus.

    PubMed

    Higo, S; Honda, S; Iijima, N; Ozawa, H

    2016-04-01

    The neuropeptide kisspeptin and its receptor play an essential role in reproduction as a potent modulator of the gonadotrophin-releasing hormone (GnRH) neurone. In addition to its reproductive function, kisspeptin signalling is also involved in extra-hypothalamic-pituitary-gonadal (HPG) axis systems, including oxytocin and arginine vasopressin (AVP) secretion. By contrast to the accumulating information for kisspeptin neurones and kisspeptin fibres, the histological distribution and function of the kisspeptin receptor in the rat brain remain poorly characterised. Using in situ hybridisation combined with immunofluorescence, the present study aimed to determine the whole brain map of Kiss1r mRNA (encoding the kisspeptin receptor), and to examine whether oxytocin or AVP neurones express Kiss1r. Neurones with strong Kiss1r expression were observed in several rostral brain areas, including the olfactory bulb, medial septum, diagonal band of Broca and throughout the preoptic area, with the most concentrated population being around 0.5 mm rostral to the bregma. Co-immunofluorescence staining revealed that, in these rostral brain areas, the vast majority of the Kiss1r-expressing neurones co-expressed GnRH. Moderate levels of Kiss1r mRNA were also noted in the rostral periventricular area, paraventricular nucleus (PVN), and throughout the arcuate nucleus. Relatively weak Kiss1r expression was observed in the supraoptic nucleus and supramammillary nuclei. Moderate to weak expression of Kiss1r was also observed in several regions in the midbrain, including the periaqueductal gray and dorsal raphe nucleus. We also examined whether oxytocin and AVP neurones in the PVN co-express Kiss1r. Immunofluorescence revealed the co-expression of Kiss1r in a subset of the oxytocin neurones but not in the AVP neurones in the PVN. The present study provides a fundamental anatomical basis for further examination of the kisspeptin signalling system in the extra-HPG axis, as well as in

  17. Median Arcuate Ligament Syndrome Confirmed with the Use of Intravascular Ultrasound

    PubMed Central

    de Lara, Fernando Vazquez; Higgins, Christopher

    2014-01-01

    Median arcuate ligament syndrome, a rarely reported condition, is characterized by postprandial abdominal pain, nausea, vomiting, and weight loss. Its cause is unclear. We present the case of a 45-year-old woman who had intermittent chronic positional abdominal pain without weight loss. Magnetic resonance angiograms and computed tomograms revealed stenosis of the celiac artery. Ostial compression was confirmed on catheter angiographic and intravascular ultrasonographic images. Intravascular ultrasound revealed far greater stenosis than did the initial imaging methods and confirmed a diagnosis of median arcuate ligament syndrome. In lieu of surgery, the patient underwent a celiac ganglion block procedure that substantially relieved her symptoms. To our knowledge, this is the first report of the use of intravascular ultrasound in the diagnosis of median arcuate ligament syndrome. We recommend using this imaging method preoperatively in other suspected cases of the syndrome, to better identify patients who might benefit from corrective surgery. PMID:24512402

  18. The neuropeptide bursicon acts in cuticle metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bursicon is a heterodimeric neuropeptide formed of bursicon a (burs a) and bursicon B (burs B) that controls cuticle tanning and wing expansion in insects. Burs a-a and burs B-B homodimers are also formed; they act via an unknown receptor to induce expression of prophylactic immune and stress genes ...

  19. Neuropeptides: conductors of the immune orchestra.

    PubMed

    Morley, J E; Kay, N E; Solomon, G F; Plotnikoff, N P

    1987-08-01

    There is increasing evidence for a bidirectional communications system between the immune system and the brain. Many of the substances involved in this communication appear to be neuropeptides. These findings have given biochemical validity to the clinical and epidemiological studies that have suggested that psychosocial factors can modulate the response to infections and neoplasms. PMID:3298913

  20. Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales

    PubMed Central

    Mandelblat-Cerf, Yael; Ramesh, Rohan N; Burgess, Christian R; Patella, Paola; Yang, Zongfang; Lowell, Bradford B; Andermann, Mark L

    2015-01-01

    Agouti-related-peptide (AgRP) neurons—interoceptive neurons in the arcuate nucleus of the hypothalamus (ARC)—are both necessary and sufficient for driving feeding behavior. To better understand the functional roles of AgRP neurons, we performed optetrode electrophysiological recordings from AgRP neurons in awake, behaving AgRP-IRES-Cre mice. In free-feeding mice, we observed a fivefold increase in AgRP neuron firing with mounting caloric deficit in afternoon vs morning recordings. In food-restricted mice, as food became available, AgRP neuron firing dropped, yet remained elevated as compared to firing in sated mice. The rapid drop in spiking activity of AgRP neurons at meal onset may reflect a termination of the drive to find food, while residual, persistent spiking may reflect a sustained drive to consume food. Moreover, nearby neurons inhibited by AgRP neuron photostimulation, likely including satiety-promoting pro-opiomelanocortin (POMC) neurons, demonstrated opposite changes in spiking. Finally, firing of ARC neurons was also rapidly modulated within seconds of individual licks for liquid food. These findings suggest novel roles for antagonistic AgRP and POMC neurons in the regulation of feeding behaviors across multiple timescales. DOI: http://dx.doi.org/10.7554/eLife.07122.001 PMID:26159614

  1. Zinc regulation of food intake: new insights on the role of neuropeptide Y.

    PubMed

    Levenson, Cathy W

    2003-07-01

    The role of neuropeptide Y (NPY) in feeding behavior and zinc deficiency-induced anorexia has been controversial because hypothalamic NPY levels are elevated in both zinc deficiency and food restriction. A recent report shows that while NPY is released from terminals in the paraventricular nucleus of the hypothalamus of food-restricted animals, this release is significantly impaired in zinc-deficient animals. Zinc deficiency may therefore cause anorexia by inhibiting the release of NPY that is required for receptor activation. PMID:12918877

  2. All-arthroscopic repair of arcuate avulsion fracture with suture anchor.

    PubMed

    Zhang, Hui; Hong, Lei; Wang, Xue-Song; Zhang, Jin; Liu, Xin; Feng, Hua

    2011-05-01

    Arcuate avulsion fractures are very rare but present pathologic posterolateral rotation instability. Untreated instability may lead to overload of the reconstructed posterior cruciate ligament (PCL) graft. Surgical treatment and clinical results have not yet been reported to our knowledge. This study presents the case of a 45-year-old man with PCL injury and an arcuate avulsion fracture of the fibular head. The dial test was positive preoperatively, and magnetic resonance imaging showed an "arcuate" sign. The avulsed bone fragment was reduced and fixed with a suture anchor by an all-arthroscopic technique. At the 1-year follow-up, the patient had resumed all his normal activities, including sports. He scored 1+ on the posterior drawer test, and external rotation was 1° less than that in his contralateral normal knee. Compared with the values in the contralateral normal knee, the posterior tibial translation was reduced from 15.5 mm preoperatively to 6.3 mm postoperatively. The postoperative magnetic resonance imaging and computed tomography scans showed that the reconstructed PCL graft and the osseous fragment of the styloid process of the fibular head attached to the popliteofibular ligament were reduced. This technical note describes an all-arthroscopic reduction and fixation technique of arcuate avulsed fracture of the fibular head. PMID:21398077

  3. Anatomical Properties of the Arcuate Fasciculus Predict Phonological and Reading Skills in Children

    ERIC Educational Resources Information Center

    Yeatman, Jason D.; Dougherty, Robert F.; Rykhlevskaia, Elena; Sherbondy, Anthony J.; Deutsch, Gayle K.; Wandell, Brian A.; Ben-Shachar, Michal

    2011-01-01

    For more than a century, neurologists have hypothesized that the arcuate fasciculus carries signals that are essential for language function; however, the relevance of the pathway for particular behaviors is highly controversial. The primary objective of this study was to use diffusion tensor imaging to examine the relationship between individual…

  4. Elucidation of the anatomy of a satiety network: Focus on connectivity of the parabrachial nucleus in the adult rat.

    PubMed

    Zséli, Györgyi; Vida, Barbara; Martinez, Anais; Lechan, Ronald M; Khan, Arshad M; Fekete, Csaba

    2016-10-01

    We hypothesized that brain regions showing neuronal activation after refeeding comprise major nodes in a satiety network, and tested this hypothesis with two sets of experiments. Detailed c-Fos mapping comparing fasted and refed rats was performed to identify candidate nodes of the satiety network. In addition to well-known feeding-related brain regions such as the arcuate, dorsomedial, and paraventricular hypothalamic nuclei, lateral hypothalamic area, parabrachial nucleus (PB), nucleus of the solitary tract and central amygdalar nucleus, other refeeding activated regions were also identified, such as the parastrial and parasubthalamic nuclei. To begin to understand the connectivity of the satiety network, the interconnectivity of PB with other refeeding-activated neuronal groups was studied following administration of anterograde or retrograde tracers into the PB. After allowing for tracer transport time, the animals were fasted and then refed before sacrifice. Refeeding-activated neurons that project to the PB were found in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamic area; arcuate, paraventricular, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; parasubthalamic nucleus; central amygdalar nucleus; area postrema; and nucleus of the solitary tract. Axons originating from the PB were observed to closely associate with refeeding-activated neurons in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamus; paraventricular, arcuate, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; central amygdalar nucleus; parasubthalamic nucleus; ventral posterior thalamic nucleus; area postrema; and nucleus of the solitary tract. These data indicate that the PB has bidirectional connections with most refeeding-activated neuronal groups, suggesting that short-loop feedback circuits exist in this satiety network. J. Comp. Neurol. 524:2803-2827, 2016. © 2016 Wiley Periodicals, Inc. PMID:26918800

  5. The distribution of neuropeptide Y and dynorphin immunoreactivity in the brain and pituitary gland of the platyfish, Xiphophorus maculatus, from birth to sexual maturity

    NASA Technical Reports Server (NTRS)

    Cepriano, L. M.; Schreibman, M. P.

    1993-01-01

    Immunoreactive neuropeptide Y and dynorphin have been localized in the brain and pituitary gland of the platyfish, Xiphophorus maculatus, at different ages and stages of development from birth to sexual maturity. Immunoreactive neuropeptide Y was found in perikarya and tracts of the nucleus olfactoretinalis, telencephalon, ventral tegmentum and in the neurohypophysis and in the three regions of the adenohypophysis. Immunoreactive dynorphin was found in nerve tracts in the olfactory bulb and in cells of the pars intermedia and the rostral pars distalis of the pituitary gland.

  6. Neuropeptides in depression: role of VGF

    PubMed Central

    Thakker-Varia, Smita; Alder, Janet

    2009-01-01

    The monoamine hypothesis of depression is increasingly called into question by newer theories that revolve around changes in neuronal plasticity, primarily in the hippocampus, at both the structural and functional levels. Chronic stress negatively regulates hippocampal function while antidepressants ameliorate the effects of stress on neuronal morphology and activity. Both stress and antidepressants have been shown to affect levels of brain-derived neurotrophic factor (BDNF) whose transcription is dependent on cAMP response element binding protein (CREB). BDNF itself has antidepressant-like actions and can induce transcription of a number of molecules. One class of genes regulated by both BDNF and serotonin (5-HT) are neuropeptides including VGF (non-acryonimic) which has a novel role in depression. Neuropeptides are important modulators of neuronal function but their role in affective disorders is just emerging. Recent studies demonstrate that VGF, which is also a CREB-dependent gene, is upregulated by antidepressant drugs and voluntary exercise and is reduced in animal models of depression. VGF enhances hippocampal synaptic plasticity as well as neurogenesis in the dentate gyrus but the mechanisms of antidepressant-like actions of VGF in behavioral paradigms are not known. We summarize experimental data describing the roles of BDNF, VGF and other neuropeptides in depression and how they may be acting through the generation of new neurons and altered synaptic activity. Understanding the molecular and cellular changes that underlie the actions of neuropeptides and how these adaptations result in antidepressant-like effects will aid in developing drugs that target novel pathways for major depressive disorders. PMID:18983874

  7. Relation between pulpal neuropeptides and dental caries

    PubMed Central

    Kangarlou Haghighi, Ali; Nafarzadeh, Shima; Shantiaee, Yazdan; Naseri, Mandana; Ahangari, Zohreh

    2010-01-01

    INTRODUCTION: Dental pulp has neural fibers that produce neuropeptides like Substance P (SP) and calcitonin gene-related peptide (CGRP). The inflammation of dental pulp can lead to an increase amount of SP and CGRP release, especially in symptomatic irreversible pulpitis. Therefore, it can be assumed that neuropeptides have some role in the progression of inflammation of the dental pulp. The aim of this study was to determine the relation between the presence and concentration of neuropeptides in dental pulps of carious teeth caries. MATERIALS AND METHODS: For this purpose, pulpal tissues were collected from 40 teeth (20 carious and 20 intact). Pulpal samples were cultured for 72 hours. ELISA reader was used for the detection of SP and CGRP in supernatant fluids. Statistical analysis was made by Mann-Whitney U and Chi square tests. RESULTS: SP and CGRP were present in 65% and 20% of inflamed pulpal samples, respectively and 40% and 5% of normal pulpal samples, respectively. Level of SP was significantly higher in inflamed pulp samples compared to intact pulps; however, there was no statistical difference when the other groups and neuropeptides were compared. The mean concentration of SP in normal pulps was 3.4 times greater than that of CGRP; interestingly in inflamed pulps the concentration of SP was 22.3 times greater than CGRP. CONCLUSION: We can conclude that in inflamed dental pulps, the concentration of SP is higher than CGRP. It can be hypothesized that CGRP has less effect on the inflammatory changes of dental pulps. PMID:24778684

  8. Coexpression analysis of nine neuropeptides in the neurosecretory preoptic area of larval zebrafish

    PubMed Central

    Herget, Ulrich; Ryu, Soojin

    2015-01-01

    The paraventricular nucleus (PVN) of the hypothalamus in mammals coordinates neuroendocrine, autonomic and behavioral responses pivotal for homeostasis and the stress response. A large amount of studies in rodents has documented that the PVN contains diverse neuronal cell types which can be identified by the expression of distinct secretory neuropeptides. Interestingly, PVN cell types often coexpress multiple neuropeptides whose relative coexpression levels are subject to environment-induced plasticity. Due to their small size and transparency, zebrafish larvae offer the possibility to comprehensively study the development and plasticity of the PVN in large groups of intact animals, yet important anatomical information about the larval zebrafish PVN-homologous region has been missing. Therefore we recently defined the location and borders of the larval neurosecretory preoptic area (NPO) as the PVN-homologous region in larval zebrafish based on transcription factor expression and cell type clustering. To identify distinct cell types present in the larval NPO, we also generated a comprehensive 3D map of 9 zebrafish homologs of typical neuropeptides found in the mammalian PVN (arginine vasopressin (AVP), corticotropin-releasing hormone (CRH), proenkephalin a (penka)/b (penkb), neurotensin (NTS), oxytocin (OXT), vasoactive intestinal peptide (VIP), cholecystokinin (CCK), and somatostatin (SST)). Here we extend this chemoarchitectural map to include the degrees of coexpression of two neuropeptides in the same cell by performing systematic pairwise comparisons. Our results allowed the subclassification of NPO cell types, and differences in variability of coexpression profiles suggest potential targets of biochemical plasticity. Thus, this work provides an important basis for the analysis of the development, function, and plasticity of the primary neuroendocrine brain region in larval zebrafish. PMID:25729355

  9. Neuropeptide Regulation of Fear and Anxiety: Implications of Cholecystokinin, Endogenous Opioids, and Neuropeptide Y

    PubMed Central

    Bowers, Mallory E.; Choi, Dennis C.; Ressler, Kerry J.

    2012-01-01

    The neural circuitry of fear likely underlies anxiety and fear-related disorders such as specific and social phobia, panic disorder, and posttraumatic stress disorder. The primary pharmacological treatments currently utilized for these disorders include benzodiazepines, which act on the GABAergic receptor system, and antidepressants, which modulate the monamine systems. However, recent work on the regulation of fear neural circuitry suggests that specific neuropeptide modulation of this system is of critical importance. Recent reviews have examined the roles of the hypothalamic-pituitary-adrenal axis neuropeptides as well as the roles of neurotrophic factors in regulating fear. The present review, instead, will focus on three neuropeptide systems which have received less attention in recent years but which are clearly involved in regulating fear and its extinction. The endogenous opioid system, particularly activating the μ opioid receptors, has been demonstrated to regulate fear expression and extinction, possibly through functioning as an error signal within the amygdala to mark unreinforced conditioned stimuli. The cholecystokinin (CCK) system initially led to much excitement through its potential role in panic disorder. More recent work in the CCK neuropeptide pathway suggests that it may act in concordance with the endogenous cannabinoid system in the modulation of fear inhibition and extinction. Finally, older as well as very recent data suggests that neuropeptide Y (NPY) may play a very interesting role in counteracting stress effects, enhancing extinction, and enhancing resilience in fear and stress preclinical models. Future work in understanding the mechanisms of neuropeptide functioning, particularly within well-known behavioral circuits, are likely to provide fascinating new clues into the understanding of fear behavior as well as suggesting novel therapeutics for treating disorders of anxiety and fear dysregulation. PMID:22429904

  10. Neuropeptides in the Gonads: From Evolution to Pharmacology

    PubMed Central

    McGuire, Nicolette L.; Bentley, George E.

    2010-01-01

    Vertebrate gonads are the sites of synthesis and binding of many peptides that were initially classified as neuropeptides. These gonadal neuropeptide systems are neither well understood in isolation, nor in their interactions with other neuropeptide systems. Further, our knowledge of the control of these gonadal neuropeptides by peripheral hormones that bind to the gonads, and which themselves are under regulation by true neuropeptide systems from the hypothalamus, is relatively meager. This review discusses the existence of a variety of neuropeptides and their receptors which have been discovered in vertebrate gonads, and the possible way in which such systems could have evolved. We then focus on two key neuropeptides for regulation of the hypothalamo-pituitary-gonadal axis: gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH). Comparative studies have provided us with a degree of understanding as to how a gonadal GnRH system might have evolved, and they have been responsible for the discovery of GnIH and its gonadal counterpart. We attempt to highlight what is known about these two key gonadal neuropeptides, how their actions differ from their hypothalamic counterparts, and how we might learn from comparative studies of them and other gonadal neuropeptides in terms of pharmacology, reproductive physiology and evolutionary biology. PMID:21607065

  11. Identification of a new member of PBAN family of neuropeptides from the fire ant, Solenopsis invicta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neuropeptide hormones produced by neurosecretory cells in the central or peripheral nervous systems regulate various physiological and behavioral events during insect development and reproduction. Pyrokinin/Pheromone Biosynthesis Activating Neuropeptide (PBAN) is a major neuropeptide family, chara...

  12. Effect of progesterone on kisspeptin and neurokinin B cell numbers in the arcuate nucleus of the female pig

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Progesterone acts at the hypothalamus to inhibit LH secretion in the pig, but the mechanism for this is unknown. Kisspeptin and neurokinin B (NKB) have both been shown to influence GnRH/LH secretion and mediate steroid negative feedback in several species and to be critical for normal reproductive f...

  13. Apolipoprotein A-IV inhibits AgRP/NPY neurons and activates POMC neurons in the arcuate nucleus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Apolipoprotein A-IV (apoA-IV) in the brain potently suppresses food intake. However the mechanisms underlying its anorexigenic effects remain to be identified. We first examined the effects of apoA-IV on cellular activities in hypothalamic neurons that co-express agouti-related peptide (AgRP) and ne...

  14. Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution.

    PubMed

    Semmens, Dean C; Mirabeau, Olivier; Moghul, Ismail; Pancholi, Mahesh R; Wurm, Yannick; Elphick, Maurice R

    2016-02-01

    Neuropeptides are evolutionarily ancient mediators of neuronal signalling in nervous systems. With recent advances in genomics/transcriptomics, an increasingly wide range of species has become accessible for molecular analysis. The deuterostomian invertebrates are of particular interest in this regard because they occupy an 'intermediate' position in animal phylogeny, bridging the gap between the well-studied model protostomian invertebrates (e.g. Drosophila melanogaster, Caenorhabditis elegans) and the vertebrates. Here we have identified 40 neuropeptide precursors in the starfish Asterias rubens, a deuterostomian invertebrate from the phylum Echinodermata. Importantly, these include kisspeptin-type and melanin-concentrating hormone-type precursors, which are the first to be discovered in a non-chordate species. Starfish tachykinin-type, somatostatin-type, pigment-dispersing factor-type and corticotropin-releasing hormone-type precursors are the first to be discovered in the echinoderm/ambulacrarian clade of the animal kingdom. Other precursors identified include vasopressin/oxytocin-type, gonadotropin-releasing hormone-type, thyrotropin-releasing hormone-type, calcitonin-type, cholecystokinin/gastrin-type, orexin-type, luqin-type, pedal peptide/orcokinin-type, glycoprotein hormone-type, bursicon-type, relaxin-type and insulin-like growth factor-type precursors. This is the most comprehensive identification of neuropeptide precursor proteins in an echinoderm to date, yielding new insights into the evolution of neuropeptide signalling systems. Furthermore, these data provide a basis for experimental analysis of neuropeptide function in the unique context of the decentralized, pentaradial echinoderm bauplan. PMID:26865025

  15. Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution

    PubMed Central

    Semmens, Dean C.; Mirabeau, Olivier; Moghul, Ismail; Pancholi, Mahesh R.; Wurm, Yannick; Elphick, Maurice R.

    2016-01-01

    Neuropeptides are evolutionarily ancient mediators of neuronal signalling in nervous systems. With recent advances in genomics/transcriptomics, an increasingly wide range of species has become accessible for molecular analysis. The deuterostomian invertebrates are of particular interest in this regard because they occupy an ‘intermediate' position in animal phylogeny, bridging the gap between the well-studied model protostomian invertebrates (e.g. Drosophila melanogaster, Caenorhabditis elegans) and the vertebrates. Here we have identified 40 neuropeptide precursors in the starfish Asterias rubens, a deuterostomian invertebrate from the phylum Echinodermata. Importantly, these include kisspeptin-type and melanin-concentrating hormone-type precursors, which are the first to be discovered in a non-chordate species. Starfish tachykinin-type, somatostatin-type, pigment-dispersing factor-type and corticotropin-releasing hormone-type precursors are the first to be discovered in the echinoderm/ambulacrarian clade of the animal kingdom. Other precursors identified include vasopressin/oxytocin-type, gonadotropin-releasing hormone-type, thyrotropin-releasing hormone-type, calcitonin-type, cholecystokinin/gastrin-type, orexin-type, luqin-type, pedal peptide/orcokinin-type, glycoprotein hormone-type, bursicon-type, relaxin-type and insulin-like growth factor-type precursors. This is the most comprehensive identification of neuropeptide precursor proteins in an echinoderm to date, yielding new insights into the evolution of neuropeptide signalling systems. Furthermore, these data provide a basis for experimental analysis of neuropeptide function in the unique context of the decentralized, pentaradial echinoderm bauplan. PMID:26865025

  16. Mimetic analogs of three insect neuropeptide classes for pest management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neuropeptides are potent regulators of critical life processes in insects, but are subjected to rapid degradation by peptidases in the hemolymph (blood), tissues and gut. This limitation can be overcome via replacement of peptidase susceptible portions of the insect neuropeptides to create analogs w...

  17. Mimetic analogs of pyrokinin neuropeptides for pest management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neuropeptides are potent regulators of critical life processes in insects, but are subjected to rapid degradation by peptidases in the hemolymph (blood), tissues and gut. This limitation can be overcome via replacement of peptidase susceptible portions of the insect neuropeptides to create analogs ...

  18. METABOLISM OF AN INSECT NEUROPEPTIDE BY THE NEMATODE C. ELEGANS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We are interested in neuropeptides in nematodes as leads to new control agents for parasitic nematodes. This includes physiological aspects of neuropeptide action and metabolic regulation of these peptides. The free-living nematode Caenorhabditis elegans, with its mapped genome, offers unique opport...

  19. Segregation of acute leptin and insulin effects in distinct populations of arcuate POMC neurons

    PubMed Central

    Williams, Kevin W.; Margatho, Lisandra O.; Lee, Charlotte E.; Choi, Michelle; Lee, Syann; Scott, Michael M.; Elias, Carol F.; Elmquist, Joel K.

    2010-01-01

    Acute leptin administration results in a depolarization and concomitant increase in the firing rate of a subpopulation of arcuate POMC cells. This rapid activation of POMC cells has been implicated as a cellular correlate of leptin effects on energy balance. In contrast to leptin, insulin inhibits the activity of some POMC neurons. Several studies have described a “cross-talk” between leptin and insulin within the mediobasal hypothalamus via the intracellular enzyme, phosphoinositol-3-kinase (PI3K). Interestingly, both insulin and leptin regulate POMC cellular activity by activation of PI3K, however it is unclear if leptin and insulin effects are observed in similar or distinct populations of POMC cells. We therefore used dual label immunohistochemistry/in situ hybridization and whole-cell patch-clamp electrophysiology to map insulin and leptin responsive arcuate POMC neurons. Leptin-induced Fos activity within arcuate POMC neurons was localized separate from POMC neurons which express insulin receptor. Moreover, acute responses to leptin and insulin were largely segregated in distinct sub-populations of POMC cells. Collectively, these data suggest that cross-talk between leptin and insulin occurs within a network of cells rather than within individual POMC neurons. PMID:20164331

  20. Neuropeptide Y-like immunoreactive neurons in the human olfactory bulb.

    PubMed

    Ohm, T G; Braak, E; Probst, A; Weindl, A

    1988-06-01

    Neuropeptide Y-like (NPY) immunoreactivity was localized in the adult human olfactory bulb by the unlabeled antibody enzyme (peroxidase anti-peroxidase; PAP) technique in vibratome sections. The majority of NPY-immunoreactive somata was localized in the white matter surrounding the anterior olfactory nucleus. Immunoreactive neurons were less numerous within the anterior olfactory nucleus and within the olfactory bulb layers. NPY-immunoreactive fibres were present in the white matter, the anterior olfactory nucleus, and in the olfactory bulb layers. Fibres within the white matter were generally aligned in a straight path parallel to the long axis of the olfactory bulb and tract. Fibres within the anterior olfactory nucleus showed no clear orientation and displayed numerous branching points. Coiled plexus of NPY-immunoreactive fibres were present in the glomerular layer of the olfactory bulb. Additional characteristics of the NPY-immunoreactive neurons were studied after decolouring the chromogen and restaining the sections with aldehydefuchsin to demonstrate the presence of lipofuscin granules and also with gallocyanin chrome alum to stain the Nissl substance. This analysis showed that the neurons belong to the class of non-pigmented nerve cells. PMID:3251589

  1. Mini-review: the evolution of neuropeptide signaling.

    PubMed

    Grimmelikhuijzen, Cornelis J P; Hauser, Frank

    2012-08-10

    Neuropeptides and their G protein-coupled receptors (GPCRs) have an early evolutionary origin and are already abundant in basal animals with primitive nervous systems such as cnidarians (Hydra, jellyfishes, corals, and sea anemones). Most animals emerging after the Cnidaria belong to two evolutionary lineages, the Protostomia (to which the majority of invertebrates belong) and Deuterostomia (to which some minor groups of invertebrates, and all vertebrates belong). These two lineages split about 700 million years (Myr) ago. Many mammalian neuropeptide GPCRs have orthologues in the Protostomia and this is also true for some of the mammalian neuropeptides. Examples are oxytocin/vasopressin, GnRH, gastrin/CCK, and neuropeptide Y and their GPCRs. These results implicate that protostomes (for example insects and nematodes) can be used as models to study the biology of neuropeptide signaling. PMID:22726357

  2. Neuropeptide Y and posttraumatic stress disorder

    PubMed Central

    Sah, R; Geracioti, TD

    2016-01-01

    Resiliency to the adverse effects of extraordinary emotional trauma on the brain varies within the human population. Accordingly, some people cope better than others with traumatic stress. Neuropeptide Y (NPY) is a 36-amino-acid peptide transmitter abundantly expressed in forebrain limbic and brain stem areas that regulate stress and emotional behaviors. Studies largely in rodents demonstrate a role for NPY in promoting coping with stress. Moreover, accruing data from the genetic to the physiological implicate NPY as a potential ‘resilience-to-stress’ factor in humans. Here, we consolidate findings from preclinical and clinical studies of NPY that are of relevance to stress-associated syndromes, most prototypically posttraumatic stress disorder (PTSD). Collectively, these data suggest that reduced central nervous system (CNS) NPY concentrations or function may be associated with PTSD. We also link specific symptoms of human PTSD with extant findings in the NPY field to reveal potential physiological contributions of the neuropeptide to the disorder. In pursuit of understanding the physiological basis and treatment of PTSD, the NPY system is an attractive target. PMID:22801411

  3. Neuropeptides as lung cancer growth factors.

    PubMed

    Moody, Terry W; Moreno, Paola; Jensen, Robert T

    2015-10-01

    This manuscript is written in honor of the Festschrift for Abba Kastin. I met Abba at a Society for Neuroscience meeting and learned that he was Editor-in-Chief of the Journal Peptides. I submitted manuscripts to the journal on "Neuropeptides as Growth Factors in Cancer" and subsequently was named to the Editorial Advisory Board. Over the past 30 years I have published dozens of manuscripts in Peptides and reviewed hundreds of submitted manuscripts. It was always rewarding to interact with Abba, a consummate professional. When I attended meetings in New Orleans I would sometimes go out to dinner with him at the restaurant "Commanders Palace". When I chaired the Summer Neuropeptide Conference we were honored to have him receive the Fleur Strand Award one year in Israel. I think that his biggest editorial contribution has been the "Handbook of Biologically Active Peptides." I served as a Section Editor on "Cancer/Anticancer Peptides" and again found that it was a pleasure working with him. This review focuses on the mechanisms by which bombesin-like peptides, neurotensin and vasoactive intestinal peptide regulate the growth of lung cancer. PMID:25836991

  4. Aplysia californica neurons express microinjected neuropeptide genes.

    PubMed Central

    DesGroseillers, L; Cowan, D; Miles, M; Sweet, A; Scheller, R H

    1987-01-01

    Neuropeptide genes are expressed in specific subsets of large polyploid neurons in Aplysia californica. We have defined the transcription initiation sites of three of these neuropeptide genes (the R14, L11, and ELH genes) and determined the nucleotide sequence of the promoter regions. The genes contain the usual eucaryotic promoter signals as well as other structures of potential regulatory importance, including inverted and direct repeats. The L11 and ELH genes, which are otherwise unrelated, have homology in the promoter regions, while the R14 promoter was distinct. When cloned plasmids were microinjected into Aplysia neurons in organ culture, transitions between supercoiled, relaxed circular, and linear DNAs occurred along with ligation into high-molecular-weight species. About 20% of the microinjected neurons expressed the genes. The promoter region of the R14 gene functioned in expression of the microinjected DNA in all cells studied. When both additional 5' and 3' sequences were included, the gene was specifically expressed only in R14, suggesting that the specificity of expression is generated by a multicomponent repression system. Finally, the R14 peptide could be expressed in L11, demonstrating that it is possible to alter the transmitter phenotype of these neurons by introduction of cloned genes. Images PMID:3670293

  5. Gamma-aminobutyric acid (GABA) and neuropeptides in neural areas mediating motion-induced emesis

    NASA Technical Reports Server (NTRS)

    Damelio, F.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid and the neuropeptides substance P and Met-enkephalin in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), dorsal motor nucleus of the vagus nerve (DMNV), and lateral vestibular nucleus (LVN). Glutamic acid decarboxylase immunoreactive (GAD-IR) terminals and fibers were observed in the AP and particularly in the ASP. A gradual decrease in the density of terminals was seen towards the solitary complex. The DMNV revealed irregularly scattered GAD-IR terminals within the neuropil or closely surrounding neuronal cell bodies. The LVN, particularly the dorsal division, showed numerous axon terminals which were mostly localize around large neurons and their proximal dendrites. Substance P immunoreactive (SP-IR) terminals and fibers showed high density in the solitary complex, in particular within the lateral division. The ASP showed medium to low density of SP-IR fibers and terminals. The AP exhibited a small number of fibers and terminals irregularly distributed. The DMNV revealed a high density of SP-IR terminals and fibers that were mainly concentrated in the periphery. Very few terminals were detected in the LVN. Met-enkephalin immunoreactive (Met-Enk-IR) fibers and terminals showed high density and uniform distribution in the DMNV. Scattered terminals and fibers were observed in the AP, ASP, and NTS (particularly the lateral division). The very few fibers were observed in the LVN surrounded the neuronal cell bodies. The present report is part of a study designed to investigate the interaction between neuropeptides and conventional neurotransmitters under conditions producing motion sickness and in the process of sensory-motor adaptation.

  6. Neuropeptide Signaling in Crustaceans Probed by Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Liang, Zhidan

    Neuropeptides are one of the most diverse classes of signaling molecules whose identities and functions are not yet fully understood. They have been implicated in the regulation of a wide range of physiological processes, including feeding-related and motivated behaviors, and also environmental adaptations. In this work, improved mass spectrometry-based analytical platforms were developed and applied to the crustacean systems to characterize signaling molecules. This dissertation begins with a review of mass spectrometry-based neuropeptide studies from both temporal- and spatial-domains. This review is then followed by several chapters detailing a few research projects related to the crustacean neuropeptidomic characterization and comparative analysis. The neuropeptidome of crayfish, Orconectes rusticus is characterized for the first time using mass spectrometry-based tools. In vivo microdialysis sampling technique offers the capability of direct sampling from extracellular space in a time-resolved manner. It is used to investigate the secreted neuropeptide and neurotransmitter content in Jonah crab, Cancer borealis, in this work. A new quantitation strategy using alternative mass spectrometry data acquisition approach is developed and applied for the first time to quantify neuropeptides. Coupling of this method with microdialysis enables the study of neuropeptide dynamics concurrent with different behaviors. Proof-of-principle experiments validating this approach have been carried out in Jonah crab, Cancer borealis to study feeding- and circadian rhythm-related neuropeptide changes using micoridialysis in a time-resolved manner. This permits a close correlation between behavioral and neurochemical changes, providing potential candidates for future validation of regulatory roles. In addition to providing spatial information, mass spectrometry imaging (MSI) technique enables the characterization of signaling molecules while preserving the temporal resolution. A

  7. A neuropeptide speeds circadian entrainment by reducing intercellular synchrony

    PubMed Central

    An, Sungwon; Harang, Rich; Meeker, Kirsten; Granados-Fuentes, Daniel; Tsai, Connie A.; Mazuski, Cristina; Kim, Jihee; Doyle, Francis J.; Petzold, Linda R.; Herzog, Erik D.

    2013-01-01

    Shift work or transmeridian travel can desynchronize the body's circadian rhythms from local light–dark cycles. The mammalian suprachiasmatic nucleus (SCN) generates and entrains daily rhythms in physiology and behavior. Paradoxically, we found that vasoactive intestinal polypeptide (VIP), a neuropeptide implicated in synchrony among SCN cells, can also desynchronize them. The degree and duration of desynchronization among SCN neurons depended on both the phase and the dose of VIP. A model of the SCN consisting of coupled stochastic cells predicted both the phase- and the dose-dependent response to VIP and that the transient phase desynchronization, or “phase tumbling”, could arise from intrinsic, stochastic noise in small populations of key molecules (notably, Period mRNA near its daily minimum). The model also predicted that phase tumbling following brief VIP treatment would accelerate entrainment to shifted environmental cycles. We tested this using a prepulse of VIP during the day before a shift in either a light cycle in vivo or a temperature cycle in vitro. Although VIP during the day does not shift circadian rhythms, the VIP pretreatment approximately halved the time required for mice to reentrain to an 8-h shifted light schedule and for SCN cultures to reentrain to a 10-h shifted temperature cycle. We conclude that VIP below 100 nM synchronizes SCN cells and above 100 nM reduces synchrony in the SCN. We show that exploiting these mechanisms that transiently reduce cellular synchrony before a large shift in the schedule of daily environmental cues has the potential to reduce jet lag. PMID:24167276

  8. Neuropeptide Regulation of Signaling and Behavior in the BNST

    PubMed Central

    Kash, Thomas L.; Pleil, Kristen E.; Marcinkiewcz, Catherine A.; Lowery-Gionta, Emily G.; Crowley, Nicole; Mazzone, Christopher; Sugam, Jonathan; Hardaway, J. Andrew; McElligott, Zoe A.

    2015-01-01

    Recent technical developments have transformed how neuroscientists can probe brain function. What was once thought to be difficult and perhaps impossible, stimulating a single set of long range inputs among many, is now relatively straight-forward using optogenetic approaches. This has provided an avalanche of data demonstrating causal roles for circuits in a variety of behaviors. However, despite the critical role that neuropeptide signaling plays in the regulation of behavior and physiology of the brain, there have been remarkably few studies demonstrating how peptide release is causally linked to behaviors. This is likely due to both the different time scale by which peptides act on and the modulatory nature of their actions. For example, while glutamate release can effectively transmit information between synapses in milliseconds, peptide release is potentially slower [See the excellent review by Van Den Pol on the time scales and mechanisms of release (van den Pol, 2012)] and it can only tune the existing signals via modulation. And while there have been some studies exploring mechanisms of release, it is still not as clearly known what is required for efficient peptide release. Furthermore, this analysis could be complicated by the fact that there are multiple peptides released, some of which may act in contrast. Despite these limitations, there are a number of groups making progress in this area. The goal of this review is to explore the role of peptide signaling in one specific structure, the bed nucleus of the stria terminalis, that has proven to be a fertile ground for peptide action. PMID:25475545

  9. Control of arousal through neuropeptide afferents of the locus coeruleus.

    PubMed

    Zitnik, Gerard A

    2016-06-15

    The locus coeruleus-norepinephine (LC-NE) system is implicated in mediating several aspects of arousal. Alterations in LC neuronal discharge is associated with distinct changes in behavior, cognition, sensory processing and regulation of the sleep-wake cycle. Changes in LC output and subsequent release of NE in target brain regions help adjust arousal state to respond appropriately to environmental conditions and behavioral circumstances. One way in which LC activity is controlled is through release of endogenous neuropeptides. Based on the sleep-wake cycle and environmental cues specific neuropeptide afferent systems are activated, innervating the LC. These neuropeptides include: corticotropin releasing factor (CRF), orexin (ORX), endogenous opioids, substance P (SP), melanin-concentrating hormone (MCH), neuropeptide Y (NPY) and somatostatin (SS). This review summarizes studies examining the neuroanatomical projections of these neuropeptides, their receptors in the LC, the actions on LC neurons and downstream NE release, as well as the behavioral and cognitive effects associated individual neuropeptide-mediated innervation of the LC. Finally, the relationship between individual neuropeptides, the LC-NE system and various clinical disorders is discussed, providing evidence for possible therapeutic targets for treatment of several arousal- and stress-related disorders. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26688115

  10. NeuroPep: a comprehensive resource of neuropeptides

    PubMed Central

    Wang, Yan; Wang, Mingxia; Yin, Sanwen; Jang, Richard; Wang, Jian; Xue, Zhidong; Xu, Tao

    2015-01-01

    Neuropeptides play a variety of roles in many physiological processes and serve as potential therapeutic targets for the treatment of some nervous-system disorders. In recent years, there has been a tremendous increase in the number of identified neuropeptides. Therefore, we have developed NeuroPep, a comprehensive resource of neuropeptides, which holds 5949 non-redundant neuropeptide entries originating from 493 organisms belonging to 65 neuropeptide families. In NeuroPep, the number of neuropeptides in invertebrates and vertebrates is 3455 and 2406, respectively. It is currently the most complete neuropeptide database. We extracted entries deposited in UniProt, the database (www.neuropeptides.nl) and NeuroPedia, and used text mining methods to retrieve entries from the MEDLINE abstracts and full text articles. All the entries in NeuroPep have been manually checked. 2069 of the 5949 (35%) neuropeptide sequences were collected from the scientific literature. Moreover, NeuroPep contains detailed annotations for each entry, including source organisms, tissue specificity, families, names, post-translational modifications, 3D structures (if available) and literature references. Information derived from these peptide sequences such as amino acid compositions, isoelectric points, molecular weight and other physicochemical properties of peptides are also provided. A quick search feature allows users to search the database with keywords such as sequence, name, family, etc., and an advanced search page helps users to combine queries with logical operators like AND/OR. In addition, user-friendly web tools like browsing, sequence alignment and mapping are also integrated into the NeuroPep database. Database URL: http://isyslab.info/NeuroPep PMID:25931458

  11. NeuroPep: a comprehensive resource of neuropeptides.

    PubMed

    Wang, Yan; Wang, Mingxia; Yin, Sanwen; Jang, Richard; Wang, Jian; Xue, Zhidong; Xu, Tao

    2015-01-01

    Neuropeptides play a variety of roles in many physiological processes and serve as potential therapeutic targets for the treatment of some nervous-system disorders. In recent years, there has been a tremendous increase in the number of identified neuropeptides. Therefore, we have developed NeuroPep, a comprehensive resource of neuropeptides, which holds 5949 non-redundant neuropeptide entries originating from 493 organisms belonging to 65 neuropeptide families. In NeuroPep, the number of neuropeptides in invertebrates and vertebrates is 3455 and 2406, respectively. It is currently the most complete neuropeptide database. We extracted entries deposited in UniProt, the database (www.neuropeptides.nl) and NeuroPedia, and used text mining methods to retrieve entries from the MEDLINE abstracts and full text articles. All the entries in NeuroPep have been manually checked. 2069 of the 5949 (35%) neuropeptide sequences were collected from the scientific literature. Moreover, NeuroPep contains detailed annotations for each entry, including source organisms, tissue specificity, families, names, post-translational modifications, 3D structures (if available) and literature references. Information derived from these peptide sequences such as amino acid compositions, isoelectric points, molecular weight and other physicochemical properties of peptides are also provided. A quick search feature allows users to search the database with keywords such as sequence, name, family, etc., and an advanced search page helps users to combine queries with logical operators like AND/OR. In addition, user-friendly web tools like browsing, sequence alignment and mapping are also integrated into the NeuroPep database. Database URL: http://isyslab.info/NeuroPep PMID:25931458

  12. Neuropeptides in experimental and degenerative arthritis.

    PubMed

    Niissalo, S; Hukkanen, M; Imai, S; Törnwall, J; Konttinen, Y T

    2002-06-01

    Classical symptoms of both inflammatory and degenerative arthritides may contribute to neurogenic responses like wheal, flare, edema, and pain. Rheumatoid arthritis (RA) is an autoimmune disease with an immunogenetic background. Neurogenic inflammation has been considered to play an essential role in RA, in part because of the symmetrical involvement (cross-spinal reflexes) and the predominant involvement of the most heavily innervated small joints of the hands and the feet (highly represented in the hominiculus). In contrast, osteoarthritis (OA) is considered to arise as a result of degeneration of the hyaline articular cartilage, which secondarily results in local inflammation and pain. However, it is possible that the age-related and predominant (compared to nociceptive nerves) degeneration of the proprioceptive, kinesthetic and vasoregulatory nerves can represent the primary pathogenic events. This leads to progressive damage of tissue with extremely poor capacity for self-regeneration. Inflammation, be it primary/autoimmune or secondary/degenerative, leads to peripheral sensitization and stimulation, which may further lead to central sensitization, neurogenic amplification of the inflammatory responses and activation of the neuro-endocrine axis. Neuropeptides serve as messengers, which modulate and mediate the actions in these cascades. Accordingly, many neuropeptides have been used successfully as experimental treatments, most recently VIP, which effectively controlled collagen-induced arthritis in mice. Therefore, it can safely be concluded that better treatment/control of disease activity and pain can be achieved by blocking the cascade leading to initiation and/or amplification of inflammatory process combined with effects on central nociceptive and neuroendocrine responses. PMID:12114296

  13. Transcriptome analysis of neuropeptides and G-protein coupled receptors (GPCRs) for neuropeptides in the brown planthopper Nilaparvata lugens.

    PubMed

    Tanaka, Yoshiaki; Suetsugu, Yoshitaka; Yamamoto, Kimiko; Noda, Hiroaki; Shinoda, Tetsuro

    2014-03-01

    The genes encoding neuropeptides, neurohormones and their putative G-protein coupled receptors were identified in the brown planthopper (BPH), Nilaparvata lugens (Stål) by transcriptome analysis (RNA-seq). Forty-eight candidate genes were found to encode neuropeptides or peptide hormones. These include all known insect neuropeptides and neurohormones, with the exception of neuropeptide-like precursor 2 (NPLP2) and trissin. The gene coding for prothoracicotropic hormone (PTTH) was first identified from hemimetabolous insect. A total of 57 putative neuropeptide GPCR genes were identified and phylogenetic analysis showed most of them to be closely related to insect GPCRs. A notable finding was the occurrence of vertebrate hormone receptors, thyrotropin-releasing hormone receptor (TRHR)-like GPCR and parathyroid hormone receptor (PTHR)-like GPCRs. These results suggest that N. lugens possesses the most comprehensive neuropeptide system yet found in insects. Moreover, our findings demonstrate the power of RNA-seq as a tool for analyzing the neuropeptide-related genes in the absence of whole genome sequence information. PMID:23932938

  14. Investigating Late Amazonian Volcanotectonic Activity on Olympus Mons, Mars using Flank Vents and Arcuate Graben

    NASA Astrophysics Data System (ADS)

    Peters, S.; Christensen, P. R.

    2015-12-01

    Volcanism, a fundamental process in shaping the Martian surface, is crucial to understanding its evolution. Olympus Mons, the largest volcano on Mars, is one of several large shield volcanoes. Previous studies were technologically limited to large features associated with these constructs. With the advent of high resolution datasets, we are now able to investigate smaller features, such as flank vents and arcuate graben. Flank vents, common on polygenetic volcanoes, indicate that magma has propagated away from the main conduit and/or magma chamber. Vent morphology allows for the characterization of magma properties and eruption rates. Graben indicate extensional deformation. The distribution of graben provides information on stresses that acted on the volcano. In lieu of geophysical, spectral and in-situ data, morphology, morphometry and spatial relationships are powerful tools. We utilized high resolution image data (CTX, HiRISE and THEMIS IR) and topographic data (HRSC DTM, MOLA) to identify and characterize flank vents and graben. We observed 60 flank vents and 84 arcuate graben on Olympus Mons. Flank vents display varying morphologies and morphometries, suggesting different eruption styles and variable magma volatility. Vents occur primarily on the lower flank. This suggests magma has propagated substantial distances from the magma chamber. Observed clustering of vents may also indicate shallow magma sources. Similarly, graben are observed on the lower flank crosscutting young lava flows that have mantled portions of the escarpment. This indicates either gravitational spreading of Olympus Mons or flexure of the lithosphere in response to the load of the edifice. Collectively, the distribution of flank vents and arcuate graben suggests a similar development to that proposed for Ascraeus Mons. Based on superposition relationships and dates from previous studies, the flank vents and graben formed in the Late Amazonian (≤500 Ma).

  15. Large arcuate scars: A geological legacy of the Earth's accretionary past

    NASA Technical Reports Server (NTRS)

    Saul, J. M.

    1985-01-01

    Immediately following accretion, the surface of the Earth was densely patterned with circular scars which were the surface expressions of 3-D craterform structures. In the course of geological time these structures would have become less and less visible due to the workings of the Earth's atmosphere, surface waters, and plate tectonics regime but there is no compelling reason to assume that they have been entirely eradicated. Furthermore, a very imperfect analogy with the other inner planets suggests that geological processes may not in fact be capable of totally erasing such deep features. Some illustrative examples of arcuate scars are discussed.

  16. μ Opioid receptor A118G polymorphism in association with striatal opioid neuropeptide gene expression in heroin abusers

    PubMed Central

    Drakenberg, Katarina; Nikoshkov, Andrej; Horváth, Monika Cs; Fagergren, Pernilla; Gharibyan, Anna; Saarelainen, Kati; Rahman, Sadia; Nylander, Ingrid; Bakalkin, Georgy; Rajs, Jovan; Keller, Eva; Hurd, Yasmin L.

    2006-01-01

    μ Opioid receptors are critical for heroin dependence, and A118G SNP of the μ opioid receptor gene (OPRM1) has been linked with heroin abuse. In our population of European Caucasians (n = 118), ≈90% of 118G allelic carriers were heroin users. Postmortem brain analyses showed the OPRM1 genotype associated with transcription, translation, and processing of the human striatal opioid neuropeptide system. Whereas down-regulation of preproenkephalin and preprodynorphin genes was evident in all heroin users, the effects were exaggerated in 118G subjects and were most prominent for preproenkephalin in the nucleus accumbens shell. Reduced opioid neuropeptide transcription was accompanied by increased dynorphin and enkephalin peptide concentrations exclusively in 118G heroin subjects, suggesting that the peptide processing is associated with the OPRM1 genotype. Abnormal gene expression related to peptide convertase and ubiquitin/proteosome regulation was also evident in heroin users. Taken together, alterations in opioid neuropeptide systems might underlie enhanced opiate abuse vulnerability apparent in 118G individuals. PMID:16682632

  17. The Role of Hypothalamic Neuropeptides in Neurogenesis and Neuritogenesis

    PubMed Central

    Bakos, Jan; Zatkova, Martina; Bacova, Zuzana; Ostatnikova, Daniela

    2016-01-01

    The hypothalamus is a source of neural progenitor cells which give rise to different populations of specialized and differentiated cells during brain development. Newly formed neurons in the hypothalamus can synthesize and release various neuropeptides. Although term neuropeptide recently undergoes redefinition, small-size hypothalamic neuropeptides remain major signaling molecules mediating short- and long-term effects on brain development. They represent important factors in neurite growth and formation of neural circuits. There is evidence suggesting that the newly generated hypothalamic neurons may be involved in regulation of metabolism, energy balance, body weight, and social behavior as well. Here we review recent data on the role of hypothalamic neuropeptides in adult neurogenesis and neuritogenesis with special emphasis on the development of food intake and social behavior related brain circuits. PMID:26881105

  18. [Effects of neuropeptides on interferon production in vitro].

    PubMed

    Kul'chikov, A E; Makarenko, A N

    2008-01-01

    The study of an interferon-inducing action of neuropeptides (a cerebrolysin model) on production of interferons by human blood leukocytes has shown that neuropeptides induce gamma-interferon production in the titer 267 IU/ml that determines one of the mechanisms of a neuroimmunocorrecting effect of cerebrolysin (Ebewe, Austria) in many neurological diseases (acute stroke, brain traumas and different neuroinfectious diseases). PMID:18720720

  19. High energy nucleus-nucleus collisions

    NASA Technical Reports Server (NTRS)

    Wosiek, B.

    1986-01-01

    Experimental results on high energy nucleus-nucleus interactions are presented. The data are discussed within the framework of standard super-position models and from the point-of-view of the possible formation of new states of matter in heavy ion collisions.

  20. Left Hemisphere Diffusivity of the Arcuate Fasciculus: Influences of Autism Spectrum Disorder and Language Impairment

    PubMed Central

    Roberts, T.P.L.; Heiken, K.; Zarnow, D.; Dell, J.; Nagae, L.; Blaskey, L.; Solot, C.; Levy, S.E.; Berman, J.I.; Edgar, J.C.

    2014-01-01

    BACKGROUND AND PURPOSE There has been much discussion whether brain abnormalities associated with specific language impairment and autism with language impairment are shared or are disorder specific. Although white matter tract abnormalities are observed in both specific language impairment and autism spectrum disorders, the similarities and differences in the white matter abnormalities in these 2 disorders have not been fully determined. MATERIALS AND METHODS Diffusion tensor imaging diffusion parameters of the arcuate fasciculus were measured in 14 children with specific language impairment as well as in 16 children with autism spectrum disorder with language impairment, 18 with autism spectrum disorder without language impairment, and 25 age-matched typically developing control participants. RESULTS Language impairment and autism spectrum disorder both had (elevating) main effects on mean diffusivity of the left arcuate fasciculus, initially suggesting a shared white matter substrate abnormality. Analysis of axial and radial diffusivity components, however, indicated that autism spectrum disorder and language impairment differentially affect white matter microstructural properties, with a main effect of autism spectrum disorder on axial diffusivity and a main effect of language impairment on radial diffusivity. CONCLUSIONS Although white matter abnormalities appear similar in language impairment and autism spectrum disorder when examining broad white matter measures, a more detailed analysis indicates different mechanisms for the white matter microstructural anomalies associated with language impairment and autism spectrum disorder. PMID:24335547

  1. Locus coeruleus response to single-prolonged stress and early intervention with intranasal neuropeptide Y.

    PubMed

    Sabban, Esther L; Laukova, Marcela; Alaluf, Lishay G; Olsson, Emelie; Serova, Lidia I

    2015-12-01

    Dysregulation of the central noradrenergic system is a core feature of post-traumatic stress disorder (PTSD). Here, we examined molecular changes in locus coeruleus (LC) triggered by single-prolonged stress (SPS) PTSD model at a time when behavioral symptoms are manifested, and the effect of early intervention with intranasal neuropeptide Y (NPY). Immediately following SPS stressors, male SD rats were administered intranasal NPY (SPS/NPY) or vehicle (SPS/V). Seven days later, TH protein, but not mRNA, was elevated in LC only of the SPS/V group. Although 90% of TH positive cells expressed GR, its levels were unaltered. Compared to unstressed controls, LC of SPS/V, but not SPS/NPY, expressed less Y2 receptor mRNA with more CRHR1 mRNA in subset of animals, and elevated corticotropin-releasing hormone (CRH) in central nucleus of amygdala. Following testing for anxiety on elevated plus maze (EPM), there were significantly increased TH, DBH and NPY mRNAs in LC of SPS-treated, but not previously unstressed animals. Their levels highly correlated with each other but not with behavioral features on EPM. Thus, SPS triggers long-term noradrenergic activation and higher sensitivity to mild stressors, perhaps mediated by the up-regulation influence of amygdalar CRH input and down-regulation of Y2R presynaptic inhibition in LC. Results also demonstrate the therapeutic potential of early intervention with intranasal NPY for traumatic stress-elicited noradrenergic impairments. Single-prolonged stress (SPS)-triggered long-term changes in the locus coeruleus/norepinephrine (LC/NE) system with increased tyrosine hydroxylase (TH) protein and CRH receptor 1(CRHR1) mRNA and lower neuropeptide Y receptor 2 (Y2R) mRNA levels as well as elevated corticotropin-releasing hormone (CRH) in the central nucleus of amygdala (CeA) that were prevented by early intervention with intranasal neuropeptide Y (NPY). SPS treatment led to increased sensitivity of LC to mild stress of elevated plus maze

  2. Neuropeptide Y-like immunoreactive neurons in the suprachiasmatic-subparaventricular region in the hedgehog-tenrec.

    PubMed

    Künzle, H; Unger, J W

    1992-04-01

    The distribution of the neuropeptide Y (NPY) was studied in geniculate and peri-chiasmatic regions in the lesser hedgehog-tenrec, Echinops telfairi (Insectivora). Only few neurons demonstrated NPY-like immunoreactivity in the ventral lateral geniculate nucleus. In contrast, NPY-immunoreactive perikarya were clearly present in the suprachiasmatic nucleus (SCh) and dorsal and caudal to it. The latter region might correspond to the subparaventricular zone (SPV), recently identified in the rat as an additional area involved in processing circadian rhythms. While the distribution of a distinct cell population across nuclear boundries in both SCh and SPV might conform to the present idea of processing circadian rhythms, the presence of NPY-like immunoreactive neurons in these areas is rather unusual. In mammals, such neurons have only been demonstrated so far in the mentioned insectivore as well as in man. PMID:1515927

  3. Effect of memantine on the levels of glial cells, neuropeptides, and peptide-degrading enzymes in rat brain regions of ibotenic acid-treated alzheimer's disease model.

    PubMed

    Ahmed, M M; Hoshino, H; Chikuma, T; Yamada, M; Kato, T

    2004-01-01

    It has been implicated that glia activation plays a critical role in the progression of Alzheimer's disease (AD). However, the precise mechanism of glia activation is not clearly understood yet. In our present studies, we confirmed our previous results where change the levels of neuropeptides and peptidases in ibotenic acid (IBO) infusion into the rat nucleus basalis magnocellularis, an animal model of AD. Furthermore, we extended our study to investigate a possible protection effect of co-administration on the changes of neuropeptides, and neuronal and glial cells in IBO-infused rat brain by memantine treatment. The levels of substance P and somatostatin were decreased in the striatum and frontal cortex 1 week after IBO infusion, and recovered to the control level by memantine treatment, indicating the involvement of neuropeptides in AD pathology. Furthermore, the immunohistochemical and enzymatic studies of GFAP and CD 11b, and peptidylarginine deiminase, markers of glia, in the striatum and frontal cortex showed the increase in IBO-treated rat brain as compared with controls, while co-administration of memantine and IBO no increase of astrocytes and microglia activation was observed. The present biochemical and immunohistochemical results suggest that glia activation might play an important role to the pathology of AD, and correlate with the changes of neuropeptide levels in AD brain that is recovered by memantine treatment. PMID:15183513

  4. Neuropeptides and alcohol addiction in monkeys.

    PubMed

    van Ree, J M; Kornet, M; Goosen, C

    1994-01-01

    Neuropeptides have been implicated in experimental drug addiction. Desglycinamide (Arg8) vasopressin (DGAVP) attenuates heroin and cocaine intake during initiation of drug self-administration in rats. beta-Endorphin is self-administered in rats and a role of endogenous opioids in cocaine reward has been proposed. The present studies deal with voluntary alcohol consumption in monkeys under free choice conditions. Monkeys initiated alcohol drinking within a few days and after a stable drinking pattern was acquired increased their ethanol consumption during a short period following interruption of the alcohol supply (relapse). The alcohol drinking behavior seems under the control of reinforcement principles. DGAVP reduced the acquisition of alcohol drinking in the majority of treated monkeys. Initiation of alcohol drinking induced modifications in neuroendocrine homeostasis e.g. an increased plasma beta-endorphin. Both the opioid antagonist naltrexone and the opioid agonist morphine dose-dependently decreased alcohol intake during continuous supply and after imposed abstinence. The monkeys were more sensitive to both drugs after imposed abstinence. The effects are interpreted in the context of the endorphin compensation hypothesis of addictive behavior. It is suggested that endorphins may be particularly implicated in craving for addictive drugs and in relapse of addictive behavior. PMID:8032147

  5. The neuropeptide oxytocin modulates consumer brand relationships.

    PubMed

    Fürst, Andreas; Thron, Jesko; Scheele, Dirk; Marsh, Nina; Hurlemann, René

    2015-01-01

    Each year, companies invest billions of dollars into marketing activities to embellish brands as valuable relationship partners assuming that consumer brand relationships (CBRs) and interpersonal relationships rest upon the same neurobiological underpinnings. Given the crucial role of the neuropeptide oxytocin (OXT) in social bonding, this study tests whether OXT-based mechanisms also determine the bond between consumers and brands. We conducted a randomized, placebo-controlled study involving 101 subjects and analyzed the effect of intranasal OXT on consumers' attribution of relationship qualities to brands, brands paired with human celebrity endorsers, and familiar persons. OXT indeed promoted the attribution of relationship qualities not only in the case of social and semi-social stimuli, but also brands. Intriguingly, for subjects scoring high on autistic-like traits, the effect of OXT was completely reversed, evident in even lower relationship qualities across all stimulus categories. The importance of OXT in a CBR context is further corroborated by a three-fold increase in endogenous release of OXT following exposure to one's favorite brand and positive associations between baseline peripheral OXT concentrations and brand relationship qualities. Collectively, our findings indicate that OXT not only plays a fundamental role in developing interpersonal relationships, but also enables relationship formation with objects such as brands. PMID:26449882

  6. The neuropeptide oxytocin modulates consumer brand relationships

    PubMed Central

    Fürst, Andreas; Thron, Jesko; Scheele, Dirk; Marsh, Nina; Hurlemann, René

    2015-01-01

    Each year, companies invest billions of dollars into marketing activities to embellish brands as valuable relationship partners assuming that consumer brand relationships (CBRs) and interpersonal relationships rest upon the same neurobiological underpinnings. Given the crucial role of the neuropeptide oxytocin (OXT) in social bonding, this study tests whether OXT-based mechanisms also determine the bond between consumers and brands. We conducted a randomized, placebo-controlled study involving 101 subjects and analyzed the effect of intranasal OXT on consumers’ attribution of relationship qualities to brands, brands paired with human celebrity endorsers, and familiar persons. OXT indeed promoted the attribution of relationship qualities not only in the case of social and semi-social stimuli, but also brands. Intriguingly, for subjects scoring high on autistic-like traits, the effect of OXT was completely reversed, evident in even lower relationship qualities across all stimulus categories. The importance of OXT in a CBR context is further corroborated by a three-fold increase in endogenous release of OXT following exposure to one’s favorite brand and positive associations between baseline peripheral OXT concentrations and brand relationship qualities. Collectively, our findings indicate that OXT not only plays a fundamental role in developing interpersonal relationships, but also enables relationship formation with objects such as brands. PMID:26449882

  7. Neuropeptide Y in the olfactory microvillar cells.

    PubMed

    Montani, Giorgia; Tonelli, Simone; Elsaesser, Rebecca; Paysan, Jacques; Tirindelli, Roberto

    2006-07-01

    This paper examines a possible role of microvillar cells in coordinating cell death and regeneration of olfactory epithelial neurons. The olfactory neuroepithelium of mammals is a highly dynamic organ. Olfactory neurons periodically degenerate by apoptosis and as a consequence of chemical or physical damage. To compensate for this loss of cells, the olfactory epithelium maintains a lifelong ability to regenerate from a pool of resident multipotent stem cells. To assure functional continuity and histological integrity of the olfactory epithelium over a period of many decades, apoptosis and regeneration require to be precisely coordinated. Among the factors that have been implicated in mediating this regulation is the neuropeptide Y (NPY). Knockout mice that lack functional expression of this neurogenic peptide show defects in embryonic development of the olfactory epithelium and in its ability to regenerate in the adult. Here we show that, in postnatal olfactory epithelia, NPY is exclusively expressed by a specific population of microvillar cells. We previously characterized these cells as a novel type of putative chemosensory cells, which are provided with a phosphatidyl-inositol-mediated signal transduction cascade. Our findings allow for the first time to suggest that microvillar cells are involved in connecting apoptosis to neuronal regeneration by stimulus-induced release of NPY. PMID:16800866

  8. A Combined fMRI and DTI Examination of Functional Language Lateralization and Arcuate Fasciculus Structure: Effects of Degree versus Direction of Hand Preference

    ERIC Educational Resources Information Center

    Propper, Ruthe E.; O'Donnell, Lauren J.; Whalen, Stephen; Tie, Yanmei; Norton, Isaiah H.; Suarez, Ralph O.; Zollei, Lilla; Radmanesh, Alireza; Golby, Alexandra J.

    2010-01-01

    The present study examined the relationship between hand preference degree and direction, functional language lateralization in Broca's and Wernicke's areas, and structural measures of the arcuate fasciculus. Results revealed an effect of degree of hand preference on arcuate fasciculus structure, such that consistently-handed individuals,…

  9. Neuropeptide-S (NPS) Receptor Genotype Modulates Basolateral Amygdala Responsiveness to Aversive Stimuli

    PubMed Central

    Dannlowski, Udo; Kugel, Harald; Franke, Friederike; Stuhrmann, Anja; Hohoff, Christa; Zwanzger, Peter; Lenzen, Thomas; Grotegerd, Dominik; Suslow, Thomas; Arolt, Volker; Heindel, Walter; Domschke, Katharina

    2011-01-01

    Recent studies point to a role of neuropeptide-S (NPS) in the etiology of anxiety disorders. In animal models, NPS and its receptor (NPSR) were shown to be highly expressed in the amygdala, a central structure in the fear circuit, also known to be hyper-responsive in anxiety disorders. Recently, a functional polymorphism in the NPSR gene (rs324981 A/T) has been associated with panic disorder and anxiety sensitivity. However, the role of NPSR gene variation in the modulation of fear-related amygdala responsiveness remains to be clarified. In 79 healthy subjects genotyped for NPSR rs324981, amygdala responses were assessed by means of fMRI. The participants were presented with fear-relevant faces in a robust emotion-processing paradigm frequently used to study amygdala responsiveness. We observed a strong association of NPSR T-alleles with right amygdala responsiveness to fear-relevant faces. The association peak was located in the BLA. Furthermore, responsiveness to aversive stimuli within this BLA cluster predicted a participant's self-reported harm avoidance but not depression level. We conclude that NPSR genotype is associated with increased amygdala responsiveness to fear-relevant stimuli. Thereby, NPSR rs324981 apparently causes an indirect effect on anxiety-related traits and potentially contributes to the pathogenesis of anxiety disorders by shaping fear-related limbic activity. PMID:21525857

  10. Nucleus-nucleus scattering at high energies

    NASA Technical Reports Server (NTRS)

    Franco, V.; Varma, G. K.

    1977-01-01

    Nucleus-nucleus scattering is treated in the Glauber approximation. The usual optical limit result, generally thought to improve as the number of nucleons in the colliding nuclei increases, is found to be the first term of a series which diverges for large nuclei. Corrections to the optical limit are obtained which provide a means of performing realistic calculations for collisions involving light nuclei. Total cross section predictions agree well with recent measurements.

  11. Multiple Neuropeptide-Coding Genes Involved in Planarian Pharynx Extension.

    PubMed

    Shimoyama, Seira; Inoue, Takeshi; Kashima, Makoto; Agata, Kiyokazu

    2016-06-01

    Planarian feeding behavior involves three steps: moving toward food, extending the pharynx from their planarian's ventral side after arriving at the food, and ingesting the food through the pharynx. Although pharynx extension is a remarkable behavior, it remains unknown what neuronal cell types are involved in its regulation. To identify neurons involved in regulating pharynx extension, we quantitatively analyzed pharynx extension and sought to identify these neurons by RNA interference (RNAi) and in situ hybridization. This assay, when performed using planarians with amputation of various body parts, clearly showed that the head portion is indispensable for inducing pharynx extension. We thus tested the effects of knockdown of brain neurons such as serotonergic, GABAergic, and dopaminergic neurons by RNAi, but did not observe any effects on pharynx extension behavior. However, animals with RNAi of the Prohormone Convertase 2 (PC2, a neuropeptide processing enzyme) gene did not perform the pharynx extension behavior, suggesting the possible involvement of neuropeptide(s in the regulation of pharynx extension. We screened 24 neuropeptide-coding genes, analyzed their functions by RNAi using the pharynx extension assay system, and identified at least five neuropeptide genes involved in pharynx extension. These was expressed in different cells or neurons, and some of them were expressed in the brain, suggesting complex regulation of planarian feeding behavior by the nervous system. PMID:27268986

  12. The neuropeptide bursicon acts in cuticle metabolism.

    PubMed

    Dong, Shengzhang; Zhang, Hongwei; Chen, Xi; Stanley, David; Yu, Xiaoping; Song, Qisheng

    2015-06-01

    Bursicon is a heterodimeric neuropeptide formed of bursicon α (burs α) and bursicon β (burs β) that controls cuticle tanning and wing expansion in insects. Burs α-α and burs β-β homodimers are also formed; they act via an unknown receptor to induce expression of prophylactic immune and stress genes during molting. Based on the hypothesis that burs β-β and/or bursicon influence expression of additional genes acting after the molt, we prepared and sequenced six Drosophila cDNA libraries from groups of flies separately injected with burs β-β, bursicon, or blank control. Compared to the control, the burs β-β treatments led to upregulation (by at least 1.5-fold) of 262 genes at 0.5 h postinjection (PI) and 298 genes at 1 h PI; 323 genes at 0.5 h PI and 269 genes at 1h PI were downregulated (by at least 0.67). Similar changes were recorded following bursicon injections. Of these genes, expression of seven transcripts encoding cuticle proteins was upregulated and three downregulated by burs β-β; expression of nine transcripts encoding cuticle proteins were upregulated and four downregulated following bursicon treatments. Expression of dozens of genes involved in chitin metabolism was altered by the experimental treatments. We recorded parallel changes in expression of selected genes by transcriptome and qPCR analysis. These findings support our hypothesis that burs β-β and bursicon influence expression of additional genes acting after the molt. We report that burs β-β and bursicon act in cuticle synthesis and degradation by regulating the expression of cuticular protein and chitin metabolizing related genes. PMID:25821138

  13. Bilateral agenesis of arcuate fasciculus demonstrated by fiber tractography in congenital bilateral perisylvian syndrome.

    PubMed

    Kilinc, Ozden; Ekinci, Gazanfer; Demirkol, Ezgi; Agan, Kadriye

    2015-03-01

    Congenital bilateral perisylvian syndrome (CBPS) is a type of cortical developmental abnormality associated with distinctive clinical and imaging features. Clinical spectrum of this syndrome is quite heterogeneous, with different degrees of neurological impairment in affected individuals. High-definition magnetic resonance imaging (MRI) has a great importance in revealing the presence of CBPS, but is limited in elucidating the heterogeneous clinical spectrum. The arcuate fasciculus (AF) is a prominent language tract in the perisylvian region interconnecting Broca and Wernicke areas, and has a high probability of being affected developmentally in CBPS. Herein, we report a case of CBPS with investigation of AF using diffusion tensor imaging (DTI) and fiber tractography in relation to clinical findings. We postulated that proven absence of AF on DTI and fiber tractography would correlate with a severe phenotype of CBPS. PMID:24852949

  14. A review of the arcuate structures in the Iberian Variscides; constraints and genetic models

    NASA Astrophysics Data System (ADS)

    Dias, R.; Ribeiro, A.; Romão, J.; Coke, C.; Moreira, N.

    2016-06-01

    The main Ibero-Armorican Arc (IAA) is essentially defined by a predominant NW-SE trend in the Iberian branch and an E-W trend in the Brittany one. However, in northern Spain it presents a 180° rotation, sometimes known as the Cantabrian Arc (CA). The relation between both arcs is controversial, being considered either as a single arc due to one tectonic event, or as the result of a polyphasic process. According to the last assumption, there is a later arcuate structure (CA), overlapping a previous major one (IAA). Whatever the models, they must be able to explain the presence of a Variscan sinistral transpression in Iberia and a dextral one in Armorica, and a deformation spanning from the Devonian to the Upper Carboniferous. Another arcuate structure, in continuity with the CA, the Central-Iberian Arc (CIA) was recently proposed mainly based upon on magnetic anomalies, geometry of major folds and Ordovician paleocurrents. The critical review of the structural, stratigraphic and geophysical data supports both the IAA and the CA, but as independent structures. However, the presence of a CIA is highly questionable and could not be supported. The complex strain pattern of the IAA and the CA could be explained by a Devonian - Carboniferous polyphasic indentation of a Gondwana promontory. In this model the CA is essentially a thin-skinned arc, while the IAA has a more complex and longer evolution that has led to a thick-skinned first order structure. Nevertheless, both arcs are essentially the result of a lithospheric bending process during the Iberian Variscides.

  15. Atlas of Central Nervous System and the first Neuropeptide from Fire Ant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In some insects, especially lepidopteran species, regulation of pheromone biosynthesis and production is under hormonal control. The neuropeptide hormone responsible, PBAN (Pheromone Biosynthesis Activating Neuropeptide), is synthesized in the subesophageal ganglion (SG) and released into the hemoly...

  16. Reproductive outcome after IVF following hysteroscopic division of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility

    PubMed Central

    Abuzeid, M.; Ghourab, G.; Abuzeid, O.; Mitwally, M.; Ashraf, M.; Diamond, M.

    2014-01-01

    Objective: To determine reproductive outcome after in-vitro fertilization/embryo transfer (IVF-ET) in women with primary infertility following hysteroscopic septoplasty of incomplete uterine septum or arcuate uterine anomaly. Methods: This is a historical cohort study. The study group consisted of 156 consecutive patients who underwent a total of 221 cycles of IVF/ET following hysteroscopic septoplasty of an incomplete uterine septum or arcuate anomaly (Group 1). The control group included 196 consecutive patients with normal endometrial cavity on hysteroscopy who underwent a total of 369 cycles of IVF/ET (Group 2). The reproductive outcome after the first cycle of IVF-ET and the best reproductive outcome of all the cycles the patient underwent were calculated. In addition, we compared the reproductive outcome in the study group based on the type of the anomalies (septum versus arcuate). Results: In the first fresh cycle, following septoplasty, there were significantly higher clinical pregnancy and delivery rates in Group 1 (60.3% and 51.3% respectively) compared to Group 2 (38.8% and 33.2% respectively). However, there was no significant difference between the two groups in the clinical pregnancy (74.4% vs. 67.3%) or in the delivery (65.4% vs. 60.2%) rates per patient, respectively. There was no significant difference in the reproductive outcome after IVF-ET between patients who previously had arcuate uterine anomaly versus incomplete uterine septum. Conclusion: Reproductive outcome of IVF-ET after hysteroscopic correction of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility is no different from women with normal uterine cavity. PMID:25593694

  17. Peptidomics for the discovery and characterization of neuropeptides and hormones

    PubMed Central

    Romanova, Elena V.; Sweedler, Jonathan V.

    2015-01-01

    The discovery of neuropeptides as signaling molecules with paracrine or hormonal regulatory functions has led to trailblazing advances in physiology and fostered the characterization of numerous neuropeptide-binding G-protein coupled receptors (GPCRs) as potential drug targets. The impact on human health has been tremendous: approximately 30% of commercial drugs act via the GPCR pathway. However, about 25% of the GPCRs encoded by the mammalian genome still lack their pharmacological identity. Searching for the orphan GPCR endogenous ligands that likely are neuropeptides has proved to be a formidable task. Here we describe the mass spectrometry-based technologies and experimental strategies that have been successful in achieving high throughput characterization of endogenous peptides in nervous and endocrine systems. PMID:26143240

  18. Job Stress and Neuropeptide Response Contributing to Food Intake Regulation

    PubMed Central

    Kim, Ki-Woong; Won, Yong Lim; Ko, Kyung Sun

    2015-01-01

    The purpose of the present study is to investigate the correlations between food intake behavior and job stress level and neuropeptide hormone concentrations. Job strain and food intake behavior were first identified using a self-reported questionnaire, concentrations of neuropeptide hormones (adiponectin, brain derived neurotrophic factor [BDNF], leptin, and ghrelin) were determined, and the correlations were analyzed. In the results, job strain showed significant correlations with adiponectin (odds ratio [OR], 1.220; 95% confidence interval [CI], 1.001~1.498; p < 0.05) and BDNF (OR, 0.793; 95% CI, 0.646~0.974; p < 0.05), and ghrelin exhibited a significant correlation with food intake score (OR, 0.911; 95% CI, 0.842~0.985, p < 0.05). These results suggest that job stress affects food intake regulation by altering the physiological concentrations of neuropeptide hormones as well as emotional status. PMID:26877843

  19. Brain neuropeptides in central ventilatory and cardiovascular regulation in trout

    PubMed Central

    Le Mével, Jean-Claude; Lancien, Frédéric; Mimassi, Nagi; Conlon, J. Michael

    2012-01-01

    Many neuropeptides and their G-protein coupled receptors (GPCRs) are present within the brain area involved in ventilatory and cardiovascular regulation but only a few mammalian studies have focused on the integrative physiological actions of neuropeptides on these vital cardio-respiratory regulations. Because both the central neuroanatomical substrates that govern motor ventilatory and cardiovascular output and the primary sequence of regulatory peptides and their receptors have been mostly conserved through evolution, we have developed a trout model to study the central action of native neuropeptides on cardio-ventilatory regulation. In the present review, we summarize the most recent results obtained using this non-mammalian model with a focus on PACAP, VIP, tachykinins, CRF, urotensin-1, CGRP, angiotensin-related peptides, urotensin-II, NPY, and PYY. We propose hypotheses regarding the physiological relevance of the results obtained. PMID:23115556

  20. Mass spectrometric map of neuropeptide expression in Ascaris suum.

    PubMed

    Yew, Joanne Y; Kutz, Kimberly K; Dikler, Sergei; Messinger, Lynn; Li, Lingjun; Stretton, Antony O

    2005-08-01

    A mass spectrometric method was used for the localization and sequence characterization of peptides in the nervous system of the parasitic nematode Ascaris suum. Mass spectrometric techniques utilizing MALDI-TOF, MALDI-TOF/TOF, and MALDI-FT instruments were combined with in situ chemical derivatization to examine the expression of known and putative neuropeptides in the A. suum nervous system. This first attempt at peptidomic characterization in A. suum mapped the expression of 39 neuropeptides, 17 of which are considered to be novel and whose expression has not been previously reported. These analyses also revealed that the peptide expression profile is unique to each nervous structure and that the majority of peptides observed belong to the RFamide family of neuropeptides. In addition, four new peptide sequences with a shared C-terminal PNFLRFamide motif are proposed based on in situ sequencing with mass spectrometry. PMID:15973679

  1. Afferent connections of the parabrachial nucleus in C57BL/6J mice

    PubMed Central

    Tokita, Kenichi; Inoue, Tomio; Boughter, John D.

    2009-01-01

    Although the mouse is an experimental model with an increasing importance in various fields of Neuroscience, the characteristics of its central gustatory pathways have not yet been well documented. Recent electrophysiological studies using the rat and hamster have revealed that taste processing in the brainstem gustatory relays is under the strong influence of inputs from forebrain gustatory structures. In the present study, we investigated the organization of afferent projections to the mouse parabrachial nucleus (PbN), which is located at a key site between the brainstem and gustatory, viscerosensory and autonomic centers in the forebrain. We made injections of the retrograde tracer Fluorogold centered around the “waist” area of the PbN, whose neurons are known to be highly responsive to taste stimuli. Retrogradely labeled neurons were found in the infralimbic, dysgranular and agranular insular cortex as well as the claustrum; the bed nucleus of the stria terminalis and the substantia innominata; the central nucleus of the amygdala; the lateral and medial preoptic areas, the paraventricular, the dorsomedial, the ventromedial, the arcuate, and the lateral hypothalamic areas; the periaqueductal gray, the substantia nigra pars compacta, and the ventral tegmental area; the supratrigeminal nucleus, rostral and caudal nucleus of the solitary tract; the parvicellular intermediate and gigantocellular reticular nucleus; the caudal and interpolar divisions of the spinal trigeminal nucleus, dorsomedial spinal trigeminal nucleus, and the area postrema. Numbers of labeled neurons in the main components of the gustatory system including the insular cortex, bed nucleus of the stria terminalis, central nucleus of the amygdala, lateral hypothalamus, and rostral nucleus of the solitary tract were quantified. These results are basically consistent with those of the previous rat and hamster studies, but some species differences were found. Functional implications of these

  2. Neuropeptides and the Microbiota-Gut-Brain Axis

    PubMed Central

    Holzer, Peter; Farzi, Aitak

    2015-01-01

    Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gut-brain axis. Current efforts in elucidating the implication of neuropeptides in the microbiota-gut-brain axis address 4 information carriers from the gut to the brain (vagal and spinal afferent neurons; immune mediators such as cytokines; gut hormones; gut microbiota-derived signalling molecules) and 4 information carriers from the central nervous system to the gut (sympathetic efferent neurons; parasympathetic efferent neurons; neuroendocrine factors involving the adrenal medulla; neuroendocrine factors involving the adrenal cortex). Apart from operating as neurotransmitters, many biologically active peptides also function as gut hormones. Given that neuropeptides and gut hormones target the same cell membrane receptors (typically G protein-coupled receptors), the two messenger roles often converge in the same or similar biological implications. This is exemplified by NPY and peptide YY (PYY), two members of the PP-fold peptide family. While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides are

  3. Neurotoxin-induced neuropeptide perturbations in striatum of neonatal rats.

    PubMed

    Karlsson, Oskar; Kultima, Kim; Wadensten, Henrik; Nilsson, Anna; Roman, Erika; Andrén, Per E; Brittebo, Eva B

    2013-04-01

    The cyanobacterial toxin β-N-methylamino-l-alanine (BMAA) is suggested to play a role in neurodegenerative disease. We have previously shown that although the selective uptake of BMAA in the rodent neonatal striatum does not cause neuronal cell death, exposure during the neonatal development leads to cognitive impairments in adult rats. The aim of the present study was to characterize the changes in the striatal neuropeptide systems of male and female rat pups treated neonatally (postnatal days 9-10) with BMAA (40-460 mg/kg). The label-free quantification of the relative levels of endogenous neuropeptides using mass spectrometry revealed that 25 peptides from 13 neuropeptide precursors were significantly changed in the rat neonatal striatum. The exposure to noncytotoxic doses of BMAA induced a dose-dependent increase of neurosecretory protein VGF-derived peptides, and changes in the relative levels of cholecystokinin, chromogranin, secretogranin, MCH, somatostatin and cortistatin-derived peptides were observed at the highest dose. In addition, the results revealed a sex-dependent increase in the relative level of peptides derived from the proenkephalin-A and protachykinin-1 precursors, including substance P and neurokinin A, in female pups. Because several of these peptides play a critical role in the development and survival of neurons, the observed neuropeptide changes might be possible mediators of BMAA-induced behavioral changes. Moreover, some neuropeptide changes suggest potential sex-related differences in susceptibility toward this neurotoxin. The present study also suggests that neuropeptide profiling might provide a sensitive characterization of the BMAA-induced noncytotoxic effects on the developing brain. PMID:23410195

  4. Disrupted Leptin Signaling in the Lateral Hypothalamus and Ventral Premammillary Nucleus Alters Insulin and Glucagon Secretion and Protects Against Diet-Induced Obesity.

    PubMed

    Denroche, Heather C; Glavas, Maria M; Tudurí, Eva; Karunakaran, Subashini; Quong, Whitney L; Philippe, Marion; Britton, Heidi M; Clee, Susanne M; Kieffer, Timothy J

    2016-07-01

    Leptin signaling in the central nervous system, and particularly the arcuate hypothalamic nucleus, is important for regulating energy and glucose homeostasis. However, the roles of extra-arcuate leptin responsive neurons are less defined. In the current study, we generated mice with widespread inactivation of the long leptin receptor isoform in the central nervous system via Synapsin promoter-driven Cre (Lepr(flox/flox) Syn-cre mice). Within the hypothalamus, leptin signaling was disrupted in the lateral hypothalamic area (LHA) and ventral premammillary nucleus (PMV) but remained intact in the arcuate hypothalamic nucleus and ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus, and nucleus of the tractus solitarius. To investigate the role of LHA/PMV neuronal leptin signaling, we examined glucose and energy homeostasis in Lepr(flox/flox) Syn-cre mice and Lepr(flox/flox) littermates under basal and diet-induced obese conditions and tested the role of LHA/PMV neurons in leptin-mediated glucose lowering in streptozotocin-induced diabetes. Lepr(flox/flox) Syn-cre mice did not have altered body weight or blood glucose levels but were hyperinsulinemic and had enhanced glucagon secretion in response to experimental hypoglycemia. Surprisingly, when placed on a high-fat diet, Lepr(flox/flox) Syn-cre mice were protected from weight gain, glucose intolerance, and diet-induced hyperinsulinemia. Peripheral leptin administration lowered blood glucose in streptozotocin-induced diabetic Lepr(flox/flox) Syn-cre mice as effectively as in Lepr(flox/flox) littermate controls. Collectively these findings suggest that leptin signaling in LHA/PMV neurons is not critical for regulating glucose levels but has an indispensable role in the regulation of insulin and glucagon levels and, may promote the development of diet-induced hyperinsulinemia and weight gain. PMID:27183315

  5. The insect capa neuropeptides impact desiccation and cold stress responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Insects are so successful because of great resistance to environmental stress, yet little is known about how such responses may be mediated by the neuroendocrine system. Results: We provide evidence that the capability (capa) neuropeptide gene and peptide are critical mediators of desic...

  6. Insight into the Molecular and Functional Diversity of Cnidarian Neuropeptides

    PubMed Central

    Takahashi, Toshio; Takeda, Noriyo

    2015-01-01

    Cnidarians are the most primitive animals to possess a nervous system. This phylum is composed of the classes Scyphozoa (jellyfish), Cubozoa (box jellyfish), and Hydrozoa (e.g., Hydra, Hydractinia), which make up the subphylum Medusozoa, as well as the class Anthozoa (sea anemones and corals). Neuropeptides have an early evolutionary origin and are already abundant in cnidarians. For example, from the cnidarian Hydra, a key model system for studying the peptides involved in developmental and physiological processes, we identified a wide variety of novel neuropeptides from Hydra magnipapillata (the Hydra Peptide Project). Most of these peptides act directly on muscle cells and induce contraction and relaxation. Some peptides are involved in cell differentiation and morphogenesis. In this review, we describe FMRFamide-like peptides (FLPs), GLWamide-family peptides, and the neuropeptide Hym-355; FPQSFLPRGamide. Several hundred FLPs have been isolated from invertebrate animals such as cnidarians. GLWamide-family peptides function as signaling molecules in muscle contraction, metamorphosis, and settlement in cnidarians. Hym-355; FPQSFLPRGamide enhances neuronal differentiation in Hydra. Recently, GLWamide-family peptides and Hym-355; FPQSFLPRGamide were shown to trigger oocyte maturation and subsequent spawning in the hydrozoan jellyfish Cytaeis uchidae. These findings suggest the importance of these neuropeptides in both developmental and physiological processes. PMID:25625515

  7. Orexin and neuropeptide Y: tissue specific expression and immunoreactivity in the hypothalamus and preoptic area of the cichlid fish Cichlasoma dimerus.

    PubMed

    Pérez Sirkin, D I; Suzuki, H; Cánepa, M M; Vissio, P G

    2013-12-01

    Neuropeptide Y (NPY) and orexin are neuropeptides involved in the regulation of feeding in vertebrates. In this study we determined the NPY and orexin mRNA tissue expression and their immunoreactivity distribution in both preoptic area and hypothalamus, regions involved in the regulation of feeding behavior. Both peptides presented a wide expression in all tissues examined. The NPY-immunoreactive (ir) cells were localized in the ventral nucleus posterioris periventricularis (NPPv) and numerous ir-NPY fibers were found in the nucleus lateralis tuberis (NLT), the nucleus recess lateralis (NRL) and the neurohypophysis. Ir-orexin cells were observed in the NPPv, dorsal NLT, ventral NLT, lateral NLT (NLTl) and the lateral NRL. Ir-orexin fibers were widespread distributed along all the hypothalamus, especially in the NLTl. Additionally, we observed the presence of ir-orexin immunostaining in adenohypophyseal cells, especially in somatotroph cells and the presence of a few ir-orexin-A fibers in the neurohypophysis. In conclusion, both peptides have an ubiquitous mRNA tissue expression and are similarly distributed in the hypothalamus and preoptic area of Cichlasoma dimerus. The presence of ir-orexin in adenohypohyseal cells and the presence of ir-orexin and NPY fibers in the neurohypophysis suggest that both peptides may play an important neuroendocrine role in anterior pituitary. PMID:24138942

  8. Effect of fasting on cocaine-amphetamine-regulated transcript, neuropeptide Y, and leptin receptor expression in the non-human primate hypothalamus.

    PubMed

    Van Vugt, Dean A; Lujan, Marla E; Froats, Mark; Krzemien, Alicja; Couceyro, Pastor R; Reid, Robert L

    2006-01-01

    Leptin is a cytokine produced by white adipose tissue that circulates in direct proportion to adiposity and is an important signal of energy balance. Leptin inhibits food intake in rodents by inhibiting the orexigenic neuropetides neuropeptide Y (NPY) and agouti regulated peptide (AgRP) and stimulating the anorexigenic neuropeptides alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine-amphetamine-regulated transcript (CART). In order to extend our understanding of neuroendocrine regulation of appetite in the primate, we determined the effect of a metabolic challenge on CART, NPY, and leptin receptor (Ob-R) messenger ribonucleic acid (mRNA) in the nonhuman primate (NHP) hypothalamus. Ten adult female rhesus monkeys were either maintained on a regular diet or fasted for two days before euthanasia. CART, NPY, and Ob-R mRNA were measured by in situ hybridization histochemistry (ISHH). A 2-day fast decreased CART expression in the ARC, increased NPY gene expression in the supraoptic nucleus (SON) and paraventricular nucleus (PVN), and increased Ob-R expression in the ventromedial nucleus (VMN). This is the first report that fasting inhibits CART expression and stimulates Ob-R expression in monkeys. Increased NPY expression in the SON and PVN, but not the ARC of fasted monkeys also is novel. With some exceptions, our observations are confirmatory of findings in rodent studies. Similarities in the neuroendocrine responses to a metabolic challenge in monkeys and rodents support extending existing hypotheses of neuroendocrine control of energy homeostasis to primates. PMID:17124379

  9. Distribution of the neuronal inputs to the ventral premammillary nucleus of male and female rats☆

    PubMed Central

    Cavalcante, Judney Cley; Bittencourt, Jackson Cioni; Elias, Carol Fuzeti

    2014-01-01

    The ventral premammillary nucleus (PMV) expresses dense collections of sex steroid receptors and receptors for metabolic cues, including leptin, insulin and ghrelin. The PMV responds to opposite sex odor stimulation and projects to areas involved in reproductive control, including direct innervation of gonadotropin releasing hormone neurons. Thus, the PMV is well positioned to integrate metabolic and reproductive cues, and control downstream targets that mediate reproductive function. In fact, lesions of PMV neurons blunt female reproductive function and maternal aggression. However, although the projections of PMV neurons have been well documented, little is known about the neuronal inputs received by PMV neurons. To fill this gap, we performed a systematic evaluation of the brain sites innervating the PMV neurons of male and female rats using the retrograde tracer subunit B of the cholera toxin (CTb). In general, we observed that males and females show a similar pattern of afferents. We also noticed that the PMV is preferentially innervated by neurons located in the forebrain, with very few projections coming from brainstem nuclei. The majority of inputs originated from the medial nucleus of the amygdala, the bed nucleus of the stria terminalis and the medial preoptic nucleus. A moderate to high density of afferents was also observed in the ventral subiculum, the arcuate nucleus and the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus. Our findings strengthen the concept that the PMV is part of the vomeronasal system and integrates the brain circuitry controlling reproductive functions. PMID:25084037

  10. Mass Spectrometric Analysis of Spatio-Temporal Dynamics of Crustacean Neuropeptides

    PubMed Central

    OuYang, Chuanzi; Liang, Zhidan; Li, Lingjun

    2014-01-01

    Neuropeptides represent one of the largest classes of signaling molecules used by nervous systems to regulate a wide range of physiological processes. Over the past several years, mass spectrometry (MS)-based strategies have revolutionized the discovery of neuropeptides in numerous model organisms, especially in decapod crustaceans. Here, we focus our discussion on recent advances in the use of MS-based techniques to map neuropeptides in spatial domain and monitoring their dynamic changes in temporal domain. These MS-enabled investigations provide valuable information about the distribution, secretion and potential function of neuropeptides with high molecular specificity and sensitivity. In situ MS imaging and in vivo microdialysis are highlighted as key technologies for probing spatio-temporal dynamics of neuropeptides in the crustacean nervous system. This review summarizes the latest advancement in MS-based methodologies for neuropeptide analysis including typical workflow and sample preparation strategies as well as major neuropeptide families discovered in decapod crustaceans. PMID:25448012

  11. Developmental process of the arcuate fasciculus from infancy to adolescence: a diffusion tensor imaging study

    PubMed Central

    Tak, Hyeong Jun; Kim, Jin Hyun; Son, Su Min

    2016-01-01

    We investigated the radiologic developmental process of the arcuate fasciculus (AF) using subcomponent diffusion tensor imaging (DTI) analysis in typically developing volunteers. DTI data were acquired from 96 consecutive typically developing children, aged 0–14 years. AF subcomponents, including the posterior, anterior, and direct AF tracts were analyzed. Success rates of analysis (AR) and fractional anisotropy (FA) values of each subcomponent tract were measured and compared. AR of all subcomponent tracts, except the posterior, showed a significant increase with aging (P < 0.05). Subcomponent tracts had a specific developmental sequence: First, the posterior AF tract, second, the anterior AF tract, and last, the direct AF tract in identical hemispheres. FA values of all subcomponent tracts, except right direct AF tract, showed correlation with subject's age (P < 0.05). Increased AR and FA values were observed in female subjects in young age (0–2 years) group compared with males (P < 0.05). The direct AF tract showed leftward hemispheric asymmetry and this tendency showed greater consolidation in older age (3–14 years) groups (P < 0.05). These findings demonstrated the radiologic developmental patterns of the AF from infancy to adolescence using subcomponent DTI analysis. The AF showed a specific developmental sequence, sex difference in younger age, and hemispheric asymmetry in older age. PMID:27482222

  12. Developmental process of the arcuate fasciculus from infancy to adolescence: a diffusion tensor imaging study.

    PubMed

    Tak, Hyeong Jun; Kim, Jin Hyun; Son, Su Min

    2016-06-01

    We investigated the radiologic developmental process of the arcuate fasciculus (AF) using subcomponent diffusion tensor imaging (DTI) analysis in typically developing volunteers. DTI data were acquired from 96 consecutive typically developing children, aged 0-14 years. AF subcomponents, including the posterior, anterior, and direct AF tracts were analyzed. Success rates of analysis (AR) and fractional anisotropy (FA) values of each subcomponent tract were measured and compared. AR of all subcomponent tracts, except the posterior, showed a significant increase with aging (P < 0.05). Subcomponent tracts had a specific developmental sequence: First, the posterior AF tract, second, the anterior AF tract, and last, the direct AF tract in identical hemispheres. FA values of all subcomponent tracts, except right direct AF tract, showed correlation with subject's age (P < 0.05). Increased AR and FA values were observed in female subjects in young age (0-2 years) group compared with males (P < 0.05). The direct AF tract showed leftward hemispheric asymmetry and this tendency showed greater consolidation in older age (3-14 years) groups (P < 0.05). These findings demonstrated the radiologic developmental patterns of the AF from infancy to adolescence using subcomponent DTI analysis. The AF showed a specific developmental sequence, sex difference in younger age, and hemispheric asymmetry in older age. PMID:27482222

  13. Atypical hemispheric asymmetry in the arcuate fasciculus of completely nonverbal children with autism.

    PubMed

    Wan, Catherine Y; Marchina, Sarah; Norton, Andrea; Schlaug, Gottfried

    2012-04-01

    Despite the fact that as many as 25% of the children diagnosed with autism spectrum disorders are nonverbal, surprisingly little research has been conducted on this population. In particular, the mechanisms that underlie their absence of speech remain unknown. Using diffusion tensor imaging, we compared the structure of a language-related white matter tract (the arcuate fasciculus, AF) in five completely nonverbal children with autism to that of typically developing children. We found that, as a group, the nonverbal children did not show the expected left-right AF asymmetry--rather, four of the five nonverbal children actually showed the reversed pattern. It is possible that this unusual pattern of asymmetry may underlie some of the severe language deficits commonly found in autism, particularly in children whose speech fails to develop. Furthermore, novel interventions (such as auditory-motor mapping training) designed to engage brain regions that are connected via the AF may have important clinical potential for facilitating expressive language in nonverbal children with autism. PMID:22524376

  14. Distinguishing the effect of lesion load from tract disconnection in the arcuate and uncinate fasciculi

    PubMed Central

    Hope, Thomas M.H.; Seghier, Mohamed L.; Prejawa, Susan; Leff, Alex P.; Price, Cathy J.

    2016-01-01

    Brain imaging studies of functional outcomes after white matter damage have quantified the severity of white matter damage in different ways. Here we compared how the outcome of such studies depends on two different types of measurements: the proportion of the target tract that has been destroyed (‘lesion load’) and tract disconnection. We demonstrate that conclusions from analyses based on two examples of these measures diverge and that conclusions based solely on lesion load may be misleading. First, we reproduce a recent lesion-load-only analysis which suggests that damage to the arcuate fasciculus, and not to the uncinate fasciculus, is significantly associated with deficits in fluency and naming skills. Next, we repeat the analysis after replacing the measures of lesion load with measures of tract disconnection for both tracts, and observe significant associations between both tracts and both language skills: i.e. the change increases the apparent relevance of the uncinate fasciculus to fluency and naming skills. Finally we show that, in this dataset, disconnection data explains significant variance in both language skills that is not accounted for by lesion load or volume, but lesion load data explains no unique variance in those skills, once disconnection and lesion volume are taken into account. PMID:26388553

  15. Detection of the arcuate fasciculus in congenital amusia depends on the tractography algorithm

    PubMed Central

    Chen, Joyce L.; Kumar, Sukhbinder; Williamson, Victoria J.; Scholz, Jan; Griffiths, Timothy D.; Stewart, Lauren

    2015-01-01

    The advent of diffusion magnetic resonance imaging (MRI) allows researchers to virtually dissect white matter fiber pathways in the brain in vivo. This, for example, allows us to characterize and quantify how fiber tracts differ across populations in health and disease, and change as a function of training. Based on diffusion MRI, prior literature reports the absence of the arcuate fasciculus (AF) in some control individuals and as well in those with congenital amusia. The complete absence of such a major anatomical tract is surprising given the subtle impairments that characterize amusia. Thus, we hypothesize that failure to detect the AF in this population may relate to the tracking algorithm used, and is not necessarily reflective of their phenotype. Diffusion data in control and amusic individuals were analyzed using three different tracking algorithms: deterministic and probabilistic, the latter either modeling two or one fiber populations. Across the three algorithms, we replicate prior findings of a left greater than right AF volume, but do not find group differences or an interaction. We detect the AF in all individuals using the probabilistic 2-fiber model, however, tracking failed in some control and amusic individuals when deterministic tractography was applied. These findings show that the ability to detect the AF in our sample is dependent on the type of tractography algorithm. This raises the question of whether failure to detect the AF in prior studies may be unrelated to the underlying anatomy or phenotype. PMID:25653637

  16. Oxytocin--a neuropeptide for affiliation: evidence from behavioral, receptor autoradiographic, and comparative studies.

    PubMed

    Insel, T R

    1992-01-01

    Oxytocin (OT) is a nine amino acid peptide synthesized in hypothalamic cells which project either to the neurohypophysis or to sites within the central nervous system. Although neurohypophyseal OT release has long been associated with uterine contraction and milk ejection, the function of intracerebral OT remains unclear. On the basis of behavioral, cellular, and comparative studies, this review suggests that brain OT influences the formation of social bonds. The first part of this review examines evidence linking central OT to several forms of affiliation. Central administration of OT induces maternal and reproductive behaviors in rats primed with gonadal steroids. OT antagonists and hypothalamic lesions block the initiation of maternal and reproductive behaviors but have no effects on these behaviors once established. Our new studies in rat pups demonstrate that central OT selectively decreases the separation response, an effect which mimics social contact. These studies of parental, reproductive, and attachment behaviors suggest that exogenous OT has "prosocial" effects and that endogenous OT may be essential for initiating social interaction. In a second series of experiments, we investigated the cellular mechanisms for OT's effects on social behavior by means of autoradiographic receptor binding. In the rat forebrain, OT receptors are expressed in several limbic regions believed to be involved in the integration of sensory processing. The regulation of these receptors is surprisingly resistant to either ablation of OT cells or repeated central administration of OT. However, receptors in two regions, the bed nucleus of the stria terminalis (BNST) and the ventromedial nucleus of the hypothalamus (VMN), appear selectively induced by exogenous or endogenous increases in gonadal steroids. At parturition, binding to OT receptors increases 84% in the BNST, and at estrus, binding increases 35% in the VMN. These results demonstrate that physiologic changes in gonadal

  17. Bidirectional iterative parcellation of diffusion weighted imaging data: Separating cortical regions connected by the arcuate fasciculus and extreme capsule

    PubMed Central

    Patterson, Dianne K.; Van Petten, Cyma; Beeson, Pélagie M.; Rapcsak, Steven Z.; Plante, Elena

    2014-01-01

    This paper introduces a Bidirectional Iterative Parcellation (BIP) procedure designed to identify the location and size of connected cortical regions (parcellations) at both ends of a white matter tract in diffusion weighted images. The procedure applies the FSL option “probabilistic tracking with classification targets” in a bidirectional and iterative manner. To assess the utility of BIP, we applied the procedure to the problem of parcellating a limited set of well-established gray matter seed regions associated with the dorsal (arcuate fasciculus/superior longitudinal fasciculus) and ventral (extreme capsule fiber system) white matter tracts in the language networks of 97 participants. These left hemisphere seed regions and the two white matter tracts, along with their right hemisphere homologues, provided an excellent test case for BIP because the resulting parcellations overlap and their connectivity via the arcuate fasciculi and extreme capsule fiber systems are well studied. The procedure yielded both confirmatory and novel findings. Specifically, BIP confirmed that each tract connects within the seed regions in unique, but expected ways. Novel findings included increasingly left-lateralized parcellations associated with the arcuate fasciculus/superior longitudinal fasciculus as a function of age and education. These results demonstrate that BIP is an easily implemented technique that successfully confirmed cortical connectivity patterns predicted in the literature, and has the potential to provide new insights regarding the architecture of the brain. PMID:25173414

  18. The neuropeptide catestatin promotes vascular smooth muscle cell proliferation through the Ca{sup 2+}-calcineurin-NFAT signaling pathway

    SciTech Connect

    Guo, Xiaoxia; Zhou, Chunyan; Sun, Ningling

    2011-04-22

    Highlights: {yields} Catestatin stimulates proliferation of vascular smooth muscle cells in a dose-dependent manner. {yields} Catestatin provokes sustained increase in intracellular Ca{sup 2+}. {yields} Catestatin produces increased activation of calcineurin and promotes NFATc1 translocation into the nucleus. -- Abstract: The Chromogranin A-derived neuropeptide catestatin is an endogenous nicotinic cholinergic antagonist that acts as a pleiotropic hormone. Since catestatin shares several functions with other members derived from the chromogranin/secretogranin protein family and other neuropeptides which exert proliferative effects on vascular smooth muscle cells (VSMCs), we therefore hypothesized that catestatin would regulate VSMC proliferation. The present study demonstrates that catestatin caused a dose-dependent induction of proliferation in rat aortic smooth muscle cells and furthermore evoked a sustained increase in intracellular calcium. This subsequently leaded to enhanced activation of the Ca{sup 2+}/calmodulin-dependent phosphatase, calcineurin and resulted in an activation of the Ca{sup 2+}-dependent transcription factor, nuclear factor of activated T cells (NFAT), initiating transcription of proliferative genes. In addition, cyclosporin A (CsA), a potent inhibitor of calcineurin, abrogated catestatin-mediated effect on VSMCs, indicating that the calcineurin-NFAT signaling is strongly required for catestatin-induced growth of VSMCs. The present study establishes catestatin as a novel proliferative cytokine on vascular smooth muscle cells and this effect is mediated by the Ca{sup 2+}-calcineurin-NFAT signaling pathway.

  19. Ambient Temperature and 17β-Estradiol Modify Fos Immunoreactivity in the Median Preoptic Nucleus, a Putative Regulator of Skin Vasomotion

    PubMed Central

    Dacks, Penny A.; Krajewski, Sally J.

    2011-01-01

    Estrogen has pronounced effects on thermoregulation, but the anatomic sites of integration between the reproductive and thermoregulatory axes are unknown. In this study, we tested whether estradiol-17β (E2) treatment would alter the activity of thermoregulatory brain regions responding to mild changes in ambient temperature (TAMBIENT). Core and tail skin temperatures were recorded at the ambient temperatures of 20, 24, or 31 C in ovariectomized (OVX) rats with and without E2. Neuronal activity was evaluated by counting the number of Fos-immunoreactive cells in the brains of rats killed 90 min after exposure to one of the three ambient temperatures. Of 14 brain areas examined, the median preoptic nucleus (MnPO) was the only site that exhibited increased Fos immunoreactivity at the high TAMBIENT of 31 C. At 24 C, OVX rats exhibited increased numbers of MnPO Fos-immunoreactive cells, compared with OVX + E2 rats. Interestingly, tail skin vasomotion and MnPO Fos expression were affected in a similar manner by TAMBIENT and E2 treatment. In the arcuate nucleus and anteroventral periventricular nucleus (AVPV), Fos immunoreactivity was highest at the low TAMBIENT of 20 C, with inhibitory (arcuate nucleus) and stimulatory (AVPV) effects of E2. No other areas responded to both TAMBIENT and E2 treatment. These results implicate the MnPO, the arcuate nucleus, and the AVPV as sites of integration between the reproductive and thermoregulatory axes. Combined with studies showing the importance of MnPO neurons in heat-defense pathways, the MnPO emerges as a likely site for E2 modulation of thermoregulatory vasomotion. PMID:21521752

  20. The Nucleus Introduced

    PubMed Central

    Pederson, Thoru

    2011-01-01

    Now is an opportune moment to address the confluence of cell biological form and function that is the nucleus. Its arrival is especially timely because the recognition that the nucleus is extremely dynamic has now been solidly established as a paradigm shift over the past two decades, and also because we now see on the horizon numerous ways in which organization itself, including gene location and possibly self-organizing bodies, underlies nuclear functions. PMID:20660024

  1. Modulation of Locomotion and Reproduction by FLP Neuropeptides in the Nematode Caenorhabditis elegans.

    PubMed

    Chang, Yan-Jung; Burton, Tina; Ha, Lawrence; Huang, Zi; Olajubelo, Adewale; Li, Chris

    2015-01-01

    Neuropeptides function in animals to modulate most, if not all, complex behaviors. In invertebrates, neuropeptides can function as the primary neurotransmitter of a neuron, but more generally they co-localize with a small molecule neurotransmitter, as is commonly seen in vertebrates. Because a single neuron can express multiple neuropeptides and because neuropeptides can bind to multiple G protein-coupled receptors, neuropeptide actions increase the complexity by which the neural connectome can be activated or inhibited. Humans are estimated to have 90 plus neuropeptide genes; by contrast, nematodes, a relatively simple organism, have a slightly larger complement of neuropeptide genes. For instance, the nematode Caenorhabditis elegans has over 100 neuropeptide-encoding genes, of which at least 31 genes encode peptides of the FMRFamide family. To understand the function of this large FMRFamide peptide family, we isolated knockouts of different FMRFamide-encoding genes and generated transgenic animals in which the peptides are overexpressed. We assayed these animals on two basic behaviors: locomotion and reproduction. Modulating levels of different neuropeptides have strong as well as subtle effects on these behaviors. These data suggest that neuropeptides play critical roles in C. elegans to fine tune neural circuits controlling locomotion and reproduction. PMID:26406995

  2. Discovery of sea urchin NGFFFamide receptor unites a bilaterian neuropeptide family

    PubMed Central

    Semmens, Dean C.; Beets, Isabel; Rowe, Matthew L.; Blowes, Liisa M.; Oliveri, Paola; Elphick, Maurice R.

    2015-01-01

    Neuropeptides are ancient regulators of physiology and behaviour, but reconstruction of neuropeptide evolution is often difficult owing to lack of sequence conservation. Here, we report that the receptor for the neuropeptide NGFFFamide in the sea urchin Strongylocentrotus purpuratus (phylum Echinodermata) is an orthologue of vertebrate neuropeptide-S (NPS) receptors and crustacean cardioactive peptide (CCAP) receptors. Importantly, this has facilitated reconstruction of the evolution of two bilaterian neuropeptide signalling systems. Genes encoding the precursor of a vasopressin/oxytocin-type neuropeptide and its receptor duplicated in a common ancestor of the Bilateria. One copy of the precursor retained ancestral features, as seen in highly conserved vasopressin/oxytocin–neurophysin-type precursors. The other copy diverged, but this took different courses in protostomes and deuterostomes. In protostomes, the occurrence of a disulfide bridge in neuropeptide product(s) of the precursor was retained, as in CCAP, but with loss of the neurophysin domain. In deuterostomes, we see the opposite scenario—the neuropeptides lost the disulfide bridge, and neurophysin was retained (as in the NGFFFamide precursor) but was subsequently lost in vertebrate NPS precursors. Thus, the sea urchin NGFFFamide precursor and receptor are ‘missing links’ in the evolutionary history of neuropeptides that control ecdysis in arthropods (CCAP) and regulate anxiety in humans (NPS). PMID:25904544

  3. Modulation of Locomotion and Reproduction by FLP Neuropeptides in the Nematode Caenorhabditis elegans

    PubMed Central

    Chang, Yan-Jung; Burton, Tina; Ha, Lawrence; Huang, Zi; Olajubelo, Adewale; Li, Chris

    2015-01-01

    Neuropeptides function in animals to modulate most, if not all, complex behaviors. In invertebrates, neuropeptides can function as the primary neurotransmitter of a neuron, but more generally they co-localize with a small molecule neurotransmitter, as is commonly seen in vertebrates. Because a single neuron can express multiple neuropeptides and because neuropeptides can bind to multiple G protein-coupled receptors, neuropeptide actions increase the complexity by which the neural connectome can be activated or inhibited. Humans are estimated to have 90 plus neuropeptide genes; by contrast, nematodes, a relatively simple organism, have a slightly larger complement of neuropeptide genes. For instance, the nematode Caenorhabditis elegans has over 100 neuropeptide-encoding genes, of which at least 31 genes encode peptides of the FMRFamide family. To understand the function of this large FMRFamide peptide family, we isolated knockouts of different FMRFamide-encoding genes and generated transgenic animals in which the peptides are overexpressed. We assayed these animals on two basic behaviors: locomotion and reproduction. Modulating levels of different neuropeptides have strong as well as subtle effects on these behaviors. These data suggest that neuropeptides play critical roles in C. elegans to fine tune neural circuits controlling locomotion and reproduction. PMID:26406995

  4. Molecular characterization and expression profiles of neuropeptide precursors in the migratory locust.

    PubMed

    Hou, Li; Jiang, Feng; Yang, Pengcheng; Wang, Xianhui; Kang, Le

    2015-08-01

    Neuropeptides serve as the most important regulatory signals in insects. Many neuropeptides and their precursors have been identified in terms of the contig sequences of whole genome information of the migratory locust (Locusta migratoria), which exhibits a typical phenotypic plasticity in morphology, behavior and physiology. However, functions of these locust neuropeptides are largely unknown. In this study, we first revised the 23 reported neuropeptide precursor genes and identified almost all the neuropeptide precursors and corresponding products in L. migratoria. We further revealed the significant expansion profiles (such as AKH) and alternative splicing of neuropeptide genes (Lom-ITP, Lom-OK and Lom-NPF1). Transcriptomic analysis indicated that several neuropeptides, such as Lom-ACP and Lom-OK, displayed development-specific expression patterns. qRT-PCR data confirmed that most neuropeptide precursors were strongly expressed in the central nervous system. Fifteen neuropeptide genes displayed different expression levels between solitarious and gregarious locusts. These findings provide valuable clues to understand neuropeptide evolution and their functional roles in basic biology and phase transition in locusts. PMID:26036749

  5. Neuropeptide signaling remodels chemosensory circuit composition in Caenorhabditis elegans

    PubMed Central

    Leinwand, Sarah G.; Chalasani, Sreekanth H.

    2013-01-01

    Neural circuits detect environmental changes and drive behavior. The routes of information flow through dense neural networks are dynamic; however, the mechanisms underlying this circuit flexibility are poorly understood. Here, we define a novel, sensory context-dependent and neuropeptide-regulated switch in the composition of a C. elegans salt sensory circuit. The primary salt detectors, ASE sensory neurons, use BLI-4 endoprotease-dependent cleavage to release the insulin-like peptide INS-6 in response to large but not small changes in external salt stimuli. Insulins, signaling through the insulin receptor DAF-2, functionally switch the AWC olfactory sensory neuron into an interneuron in the salt circuit. Animals with disrupted insulin signaling have deficits in salt attraction, suggesting that peptidergic signaling potentiates responses to high salt stimuli, which may promote ion homeostasis. Our results show that sensory context and neuropeptide signaling modify neural networks and suggest general mechanisms for generating flexible behavioral outputs by modulating neural circuit composition. PMID:24013594

  6. Neuropeptide signaling remodels chemosensory circuit composition in Caenorhabditis elegans.

    PubMed

    Leinwand, Sarah G; Chalasani, Sreekanth H

    2013-10-01

    Neural circuits detect environmental changes and drive behavior. The routes of information flow through dense neural networks are dynamic, but the mechanisms underlying this circuit flexibility are poorly understood. Here, we define a sensory context-dependent and neuropeptide-regulated switch in the composition of a C. elegans salt sensory circuit. The primary salt detectors, ASE sensory neurons, used BLI-4 endoprotease-dependent cleavage to release the insulin-like peptide INS-6 in response to large, but not small, changes in external salt stimuli. Insulins, signaling through the insulin receptor DAF-2, functionally switched the AWC olfactory sensory neuron into an interneuron in the salt circuit. Worms with disrupted insulin signaling had deficits in salt attraction, suggesting that peptidergic signaling potentiates responses to high salt stimuli, which may promote ion homeostasis. Our results indicate that sensory context and neuropeptide signaling modify neural networks and suggest general mechanisms for generating flexible behavioral outputs by modulating neural circuit composition. PMID:24013594

  7. Seasonal shoreline behaviours along the arcuate Niger Delta coast: Complex interaction between fluvial and marine processes

    NASA Astrophysics Data System (ADS)

    Dada, Olusegun A.; Li, Guangxue; Qiao, Lulu; Ding, Dong; Ma, Yanyan; Xu, Jishang

    2016-07-01

    Deltaic coasts are dynamic geomorphic systems where continuous changes occur on diverse spatial and temporal scales, and these changes constitute an important aspect of their evolution. Based on three-year satellite-derived shoreline data coupled with re-analyzed wave data and hydro-meteorological data, a comprehensive analysis of the dominant processes governing the seasonal shoreline changes along the oil-rich arcuate section of the Niger Delta, in the Nigerian Shelf of the North Atlantic Ocean has been undertaken. Shoreline analysis results show that the delta coast is characterized by predominant summer erosion and maximum winter accretion. Between 2010 and 2012, erosion dominated over accretion and a total of 9.1 km2 deltaic land was lost to coastline erosion at an annual average erosion rate of 4.55±1.21 km2/yr. A greater understanding of the dominant factors responsible for the change is presented. Shoreline change interactions with cross-shore sediment exchange processes are prominent at seasonal timescale (Summer R2=-0.85 and Winter R2=0.7), and interannual timescale (R2=-0.93) with longshore sediment transport processes. Correlation analysis reveals a gradual degeneration of relationship between the suspended sediment flux and coastal hydrodynamics beginning from 2010 to 2012 (cross-shore transport, R=0.68, 0.36 and 0.2 for 2010, 2011 and 2012, respectively; longshore transport R=0.63, 0.44 and 0.2 for 2010, 2011 and 2012, respectively). The study concludes that the effect of fluvial sediment reduction to the delta coast due to capital dredging of the Lower Niger River channels between 2009 and 2012, and periodic fluctuations in the nearshore hydrodynamics processes caused the observed annual shoreline erosion that eventually forced the deltaic coastline toward a state of landward migration during the study period.

  8. Injury of the Arcuate Fasciculus in the Dominant Hemisphere in Patients With Mild Traumatic Brain Injury

    PubMed Central

    Jang, Sung Ho; Lee, Ah Young; Shin, So Min

    2016-01-01

    Abstract Little is known about injury of the arcuate fasciculus (AF) in patients with mild traumatic brain injury (TBI). We investigated injury of the AF in the dominant hemisphere in patients with mild TBI, using diffusion tensor tractography (DTT). We recruited 25 patients with injury of the left AF among 64 right-handed consecutive patients with mild TBI and 20 normal control subjects. DTTs of the left AF were reconstructed, and fractional anisotropy (FA), apparent diffusion coefficient (ADC), and fiber number of the AF were measured. Among 64 consecutive patients, 25 (39%) patients showed injury of the left AF. The patient group showed lower FA value and fiber number with higher ADC value than the control group (P < 0.05). On K-WAB evaluation, aphasia quotient and language quotient were 95.9 ± 4.1 (range 85–100) and 95.0 ± 5.4 (range 80–100), respectively. However, 23 (92.0%) of 25 patients complained of language-related symptoms after TBI; paraphasia in 12 (48.0%) patients, deficits of comprehension in 4 (16.0%) patients, deficits of speech production in 1 (4.0%) patient, and >2 language symptoms in 6 (24.0%) patients. We found that a significant number (39%) of patients with mild TBI had injury of the AF in the dominant hemisphere and these patients had mild language deficit. These results suggest that DTT could provide useful information in detecting injury of the AF and evaluation of the AF using DTT would be necessary even in the case of a patient with mild TBI who complains of mild language deficit. PMID:26945425

  9. Arcuate fasciculus asymmetry has a hand in language function but not handedness.

    PubMed

    Allendorfer, Jane B; Hernando, Kathleen A; Hossain, Shyla; Nenert, Rodolphe; Holland, Scott K; Szaflarski, Jerzy P

    2016-09-01

    The importance of relationships between handedness, language lateralization and localization, and white matter tracts for language performance is unclear. The goal of the study was to investigate these relationships by examining arcuate fasciculus (AF) structural asymmetry (DTI) and functional asymmetry (fMRI) in language circuits, handedness, and linguistic performance. A large sample of right-handed (n = 158) and atypical-handed (n = 82) healthy adults underwent DTI at 3 T to assess number of streamlines and fractional anisotropy (FA) of the AF, and language fMRI. Language functions were assessed using standard tests of vocabulary, naming, verbal fluency, and complex ideation. Laterality indices (LIs) illustrated degree of asymmetry and lateralization patterns for the AF (streamlines and FA) and verb generation fMRI. Both handedness groups showed leftward lateralization bias for streamline and fMRI LIs and symmetry for FA LI. The proportion of subjects with left, right, or symmetric lateralization were similar between groups if based on AF LIs, but differed if based on fMRI LIs (p = 0.0016). Degree of right-handedness was not associated with AF lateralization, but was associated with fMRI language lateralization (p = 0.0014). FA LI was not associated with performance on language assessments, but streamline LI was associated with better vocabulary and complex ideation performance in atypical-handed subjects (p = 0.022 and p = 0.0098, respectively), and better semantic fluency in right-handed subjects (p = 0.047); however, these did not survive multiple comparisons correction. We provide evidence that AF asymmetry is independent of hand preference, and while degree of right-handedness is associated with hemispheric language lateralization, the majority of atypical-handed individuals are left-lateralized for language. Hum Brain Mapp 37:3297-3309, 2016. © 2016 Wiley Periodicals, Inc. PMID:27144738

  10. Local cholinergic and non-cholinergic neural pathways to the rat supraoptic nucleus

    SciTech Connect

    Meeker, M.L.

    1986-01-01

    An estimated two thirds of the input to the supraoptic nucleus of the rat hypothalamus (SON) including a functionally significant cholinergic innervation, arise from local sources of unknown origin. The sources of these inputs were identified utilizing Golgi-Cox, retrograde tracing, choline acetyltransferase immunocytochemistry and anterograde tracing methodologies. Multipolar Golgi impregnated neurons located dorsal and lateral to the SON extend spiney processes into the nucleus. Injections of the retrograde tracers, wheat germ agglutinin or wheat germ agglutinin-horseradish peroxidase, into the SON labeled cells bilaterally in the arcuate nucleus, and ipsilaterally in the lateral hypothalamus, anterior hypothalamus, nucleus of the diagonal band, subfornical organ, medial preoptic area, lateral preoptic area and in the region dorsolateral to the nucleus. Immunocytochemistry for choline acetyltransferase revealed cells within the ventro-caudal portion of cholinergic cell group, Ch4, which cluster dorsolateral to the SON, and extend axon- and dendrite-like processes into the SON. Cells double-labeled by choline acetyltransferase immunocytochemistry and retrograde tracer injections into the SON are localized within the same cholinergic cell group dorsolateral to the SON. Injections of the anterograde tracer, Phaseolus vulgaris-leucoagglutinin, deposited dorsolateral to the SON results in labeled pre-and post-synaptic processes within the SON. The identification and characterization of endogenous immunoglobulin within the SON and other neurons innervating areas lacking a blood-brain barrier established a novel and potentially important system for direct communication of the supraoptic cells with blood-borne constitutents.

  11. Possible role of neuropeptides in obsessive compulsive disorder.

    PubMed

    McDougle, C J; Barr, L C; Goodman, W K; Price, L H

    1999-01-01

    The most consistent finding in clinical research of obsessive compulsive disorder (OCD) is the significant treatment advantage of potent serotonin uptake inhibitors (SUIs) over other classes of antidepressant and antianxiety drugs. Clinical neurobiological studies of OCD, however, have yielded limited and inconsistent evidence for significant fundamental abnormalities in monoamine systems including serotonin, norepinephrine and dopamine. Furthermore, one-third to one-half of OCD patients do not experience a clinically meaningful improvement with SUI treatment. Investigation beyond the monoamine systems may be necessary in order to more fully understand the pathophysiology of obsessive-compulsive symptoms and develop improved treatments. Evidence from preclinical studies suggests that neuropeptides may have important influences on memory acquisition, maintenance and retrieval; grooming, maternal, sexual and aggressive behavior; fixed action patterns; and stereotyped behavior; these phenomena may relate to some features of OCD. In addition, extensive interactions have been identified in the brain between neuropeptidergic and monoaminergic systems, including co-localization among specific populations of neurons. The purpose of this review is to present the current knowledge of the role of neuropeptides in the clinical neurobiology of children, adolescents and adults with OCD focusing primarily on results from pharmacological challenge and cerebrospinal fluid studies. Where evidence exists, developmentally regulated differences in neuropeptide function between children and adolescents versus adults with OCD will be emphasized; these data are intended to underscore the potential importance of establishing the age of symptom onset (childhood versus adult) in individual patients with OCD participating in clinical neurobiological investigations. Likewise, where information is available, differences in measures of neuropeptides between patients with non-tic-related OCD

  12. Parasite neuropeptide biology: Seeding rational drug target selection?

    PubMed Central

    McVeigh, Paul; Atkinson, Louise; Marks, Nikki J.; Mousley, Angela; Dalzell, Johnathan J.; Sluder, Ann; Hammerland, Lance; Maule, Aaron G.

    2011-01-01

    The rationale for identifying drug targets within helminth neuromuscular signalling systems is based on the premise that adequate nerve and muscle function is essential for many of the key behavioural determinants of helminth parasitism, including sensory perception/host location, invasion, locomotion/orientation, attachment, feeding and reproduction. This premise is validated by the tendency of current anthelmintics to act on classical neurotransmitter-gated ion channels present on helminth nerve and/or muscle, yielding therapeutic endpoints associated with paralysis and/or death. Supplementary to classical neurotransmitters, helminth nervous systems are peptide-rich and encompass associated biosynthetic and signal transduction components – putative drug targets that remain to be exploited by anthelmintic chemotherapy. At this time, no neuropeptide system-targeting lead compounds have been reported, and given that our basic knowledge of neuropeptide biology in parasitic helminths remains inadequate, the short-term prospects for such drugs remain poor. Here, we review current knowledge of neuropeptide signalling in Nematoda and Platyhelminthes, and highlight a suite of 19 protein families that yield deleterious phenotypes in helminth reverse genetics screens. We suggest that orthologues of some of these peptidergic signalling components represent appealing therapeutic targets in parasitic helminths. PMID:24533265

  13. Toward a consensus nomenclature for insect neuropeptides and peptide hormones.

    PubMed

    Coast, Geoffrey M; Schooley, David A

    2011-03-01

    The nomenclature currently in use for insect neuropeptide and peptide hormone families is reviewed and suggestions are made as to how it can be rationalized. Based upon this review, a number of conventions are advanced as a guide to a more rationale nomenclature. The scheme that is put forward builds upon the binomial nomenclature scheme proposed by Raina and Gäde in 1988, when just over 20 insect neuropeptides had been identified. Known neuropeptides and peptide hormones are assigned to 32 structurally distinct families, frequently with overlapping functions. The names given to these families are those that are currently in use, and describe a biological function, homology to known invertebrate/vertebrate peptides, or a conserved structural motif. Interspecific isoforms are identified using a five-letter code to indicate genus and species names, and intraspecific isoforms are identified by Roman or Arabic numerals, with the latter used to signify the order in which sequences are encoded on a prepropeptide. The proposed scheme is sufficiently flexible to allow the incorporation of novel peptides, and could be extended to other arthropods and non-arthropod invertebrates. PMID:21093513

  14. Insect capa neuropeptides impact desiccation and cold tolerance

    PubMed Central

    Terhzaz, Selim; Teets, Nicholas M.; Cabrero, Pablo; Henderson, Louise; Ritchie, Michael G.; Nachman, Ronald J.; Dow, Julian A. T.; Denlinger, David L.; Davies, Shireen-A.

    2015-01-01

    The success of insects is linked to their impressive tolerance to environmental stress, but little is known about how such responses are mediated by the neuroendocrine system. Here we show that the capability (capa) neuropeptide gene is a desiccation- and cold stress-responsive gene in diverse dipteran species. Using targeted in vivo gene silencing, physiological manipulations, stress-tolerance assays, and rationally designed neuropeptide analogs, we demonstrate that the Drosophila melanogaster capa neuropeptide gene and its encoded peptides alter desiccation and cold tolerance. Knockdown of the capa gene increases desiccation tolerance but lengthens chill coma recovery time, and injection of capa peptide analogs can reverse both phenotypes. Immunohistochemical staining suggests that capa accumulates in the capa-expressing Va neurons during desiccation and nonlethal cold stress but is not released until recovery from each stress. Our results also suggest that regulation of cellular ion and water homeostasis mediated by capa peptide signaling in the insect Malpighian (renal) tubules is a key physiological mechanism during recovery from desiccation and cold stress. This work augments our understanding of how stress tolerance is mediated by neuroendocrine signaling and illustrates the use of rationally designed peptide analogs as agents for disrupting protective stress tolerance. PMID:25730885

  15. Ultrastructural Correlates of Enhanced Norepinephrine and Neuropeptide Y Cotransmission in the Spontaneously Hypertensive Rat Brain

    PubMed Central

    Kourtesis, Ioannis; Kasparov, Sergey; Verkade, Paul

    2015-01-01

    The spontaneously hypertensive rat (SHR) replicates many clinically relevant features of human essential hypertension and also exhibits behavioral symptoms of attention-deficit/hyperactivity disorder and dementia. The SHR phenotype is highly complex and cannot be explained by a single genetic or physiological mechanism. Nevertheless, numerous studies including our own work have revealed striking differences in central catecholaminergic transmission in SHR such as increased vesicular catecholamine content in the ventral brainstem. Here, we used immunolabeling followed by confocal microscopy and electron microscopy to quantify vesicle sizes and populations across three catecholaminergic brain areas—nucleus tractus solitarius and rostral ventrolateral medulla, both key regions for cardiovascular control, and the locus coeruleus. We also studied colocalization of neuropeptide Y (NPY) in norepinephrine and epinephrine-containing neurons as NPY is a common cotransmitter with central and peripheral catecholamines. We found significantly increased expression and coexpression of NPY in norepinephrine and epinephrine-positive neurons of locus coeruleus in SHR compared with Wistar rats. Ultrastructural analysis revealed immunolabeled vesicles of 150 to 650 nm in diameter (means ranging from 250 to 300 nm), which is much larger than previously reported. In locus coeruleus and rostral ventrolateral medulla, but not in nucleus tractus solitarius, of SHR, noradrenergic and adrenergic vesicles were significantly larger and showed increased NPY colocalization when compared with Wistar rats. Our morphological evidence underpins the hypothesis of hyperactivity of the noradrenergic and adrenergic system and increased norepinephrine and epinephrine and NPY cotransmission in specific brain areas in SHR. It further strengthens the argument for a prohypertensive role of C1 neurons in the rostral ventrolateral medulla as a potential causative factor for essential hypertension. PMID

  16. Involvement of the neuropeptide nociceptin/orphanin FQ in kainate seizures.

    PubMed

    Bregola, Gianni; Zucchini, Silvia; Rodi, Donata; Binaschi, Anna; D'Addario, Claudio; Landuzzi, Daniela; Reinscheid, Rainer; Candeletti, Sanzio; Romualdi, Patrizia; Simonato, Michele

    2002-11-15

    The neuropeptide nociceptin/orphanin FQ (N/OFQ) has been shown to modulate neuronal excitability and neurotransmitter release. Previous studies indicate that the mRNA levels for the N/OFQ precursor (proN/OFQ) are increased after seizures. However, it is unclear whether N/OFQ plays a role in seizure expression. Therefore, (1) we analyzed proN/OFQ mRNA levels and NOP (the N/OFQ receptor) mRNA levels and receptor density in the kainate model of epilepsy, using Northern blot analysis, in situ hybridization, and receptor binding assay, and (2) we examined susceptibility to kainate seizure in mice treated with 1-[(3R, 4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-benzimidazol-2-one (J-113397), a selective NOP receptor antagonist, and in proN/OFQ knock-out mice. After kainate administration, increased proN/OFQ gene expression was observed in the reticular nucleus of the thalamus and in the medial nucleus of the amygdala. In contrast, NOP mRNA levels and receptor density decreased in the amygdala, hippocampus, thalamus, and cortex. Mice treated with the NOP receptor antagonist J-113397 displayed reduced susceptibility to kainate-induced seizures (i.e., significant reduction of behavioral seizure scores). N/OFQ knock-out mice were less susceptible to kainate seizures compared with their wild-type littermates, in that lethality was reduced, latency to generalized seizure onset was prolonged, and behavioral seizure scores decreased. Intracerebroventricular administration of N/OFQ prevented reduced susceptibility to kainate seizures in N/OFQ knock-out mice. These data indicate that acute limbic seizures are associated with increased N/OFQ release in selected areas, causing downregulation of NOP receptors and activation of N/OFQ biosynthesis, and support the notion that the N/OFQ-NOP system plays a facilitatory role in kainate seizure expression. PMID:12427860

  17. Anti-aggressive effects of neuropeptide S independent of anxiolysis in male rats

    PubMed Central

    Beiderbeck, Daniela I.; Lukas, Michael; Neumann, Inga D.

    2014-01-01

    Neuropeptide S (NPS) exerts robust anxiolytic and memory enhancing effects, but only in a non-social context. In order to study whether NPS affects aggressive behavior we used Wistar rats bred for low (LAB) and high (HAB) levels of innate anxiety-related behavior, respectively, which were both described to display increased levels of aggression compared with Wistar rats not selectively bred for anxiety (NAB). Male LAB, HAB, and NAB rats were tested for aggressive behavior toward a male intruder rat within their home cage (10 min, resident-intruder [RI] test). Intracerebroventricular (icv) infusion of NPS (1 nmol) significantly reduced inter-male aggression in LAB rats, and tended to reduce aggression in HAB and NAB males. However, local infusion of NPS (0.2 or 0.1 nmol NPS) into either the nucleus accumbens or the lateral hypothalamus did not influence aggressive behavior. Social investigation in the RI test and general social motivation assessed in the social preference paradigm were not altered by icv NPS (1 nmol). The anti-aggressive effect of NPS is most likely not causally linked to its anxiolytic properties, as intraperitoneal administration of the anxiogenic drug pentylenetetrazole decreased aggression in LAB rats whereas the anxiolytic drug diazepam did not affect aggression in HAB rats. Thus, although NPS has so far only been shown to exert effects on non-social behaviors, our results are the first demonstration of anti-aggressive effects of NPS in male rats. PMID:24910598

  18. Reduced feeding response to muscimol and neuropeptide Y in senescent F344 rats.

    PubMed

    Coppola, Jessica D; Horwitz, Barbara A; Hamilton, Jock; Blevins, James E; McDonald, Roger B

    2005-06-01

    Many mammals experience spontaneous declines in their food intake and body weight near the end of life, a stage we refer to as senescence. We have previously demonstrated that senescent rats have blunted food intake responses to intracerebroventricular injections of neuropeptide Y (NPY). In the present study, we tested the hypothesis that responsiveness to GABA, a putative potentiator of NPY's effect, is also diminished. Young and old male F344 rats received injections of NPY, muscimol, (MUS, a GABA-A receptor agonist), combinations of these two agents, and vehicle [artificial cerebrospinal fluid (aCSF)] into the hypothalamic paraventricular nucleus (PVN). Both young and old presenescent rats increased their food intake in response to NPY, MUS, and the combination of the two (in comparison to injections of aCSF). The combination treatment was generally more effective than either NPY or MUS alone. These data are consistent with suggestions that both NPY and GABA play a role in the regulation of feeding behavior. Senescent rats exhibited an attenuated NPY-induced food intake, no increase in response to MUS, and a response to NPY + MUS that was no larger than that of NPY alone. We conclude that PVN injections of GABA, as well as NPY, are less effective in stimulating feeding in senescent rats and suggest that alterations in their signaling pathways play a role in the involuntary feeding decrease seen near the end of life. PMID:15731400

  19. Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair.

    PubMed

    Aoki, Miku; Watanabe, Yoshihisa; Yoshimoto, Kanji; Tsujimura, Atsushi; Yamamoto, Toshiro; Kanamura, Narisato; Tanaka, Masaki

    2016-05-01

    Serotonin 2C receptors (5-HT2 C Rs) are widely expressed in the central nervous system, and are associated with various neurological disorders. 5-HT2 C R mRNA undergoes adenosine-to-inosine RNA editing at five sites within its coding sequence, resulting in expression of 24 different isoforms. Several edited isoforms show reduced activity, suggesting that RNA editing modulates serotonergic systems in the brain with causative relevance to neuropsychiatric disorders. Transgenic mice solely expressing the non-edited 5-HT2 C R INI-isoform (INI) or the fully edited VGV-isoform exhibit various phenotypes including metabolic abnormalities, aggressive behaviour, anxiety-like behaviour, and depression-like behaviour. Here, we examined the behavioural phenotype and molecular changes of INI mice on a C57BL/6J background. INI mice showed an enhanced behavioural despair in the forced swimming test, elevated sensitivity to the tricyclic antidepressant desipramine, and significantly decreased serotonin in the nucleus accumbens (NAc), amygdala, and striatum. They also showed reduced expression of neuropeptide Y (NPY) mRNA in the NAc. In addition, by stereotactic injection of adeno-associated virus encoding NPY into the NAc, we demonstrated that accumbal NPY overexpression relieved behavioural despair. Our results suggest that accumbal NPY expression may be regulated by 5-HT2 C R RNA editing, and its impairment may be linked to mood disorders. PMID:26950265

  20. Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity

    PubMed Central

    Boughton, C K; Murphy, K G

    2013-01-01

    Obesity is a major worldwide public health issue. The physiological systems that regulate body weight are thus of great interest as targets for anti-obesity agents. Peptidergic systems are critical to the regulation of energy homeostasis by key regions in the hypothalamus and brainstem. A number of neuropeptide systems have therefore been investigated as potential treatments for obesity. Blocking orexigenic peptide signals such as neuropeptide Y, melanin-concentrating hormone, orexins, relaxin-3 and galanin-like peptide or stimulating anorectic signalling pathways used by peptides such as the melanocortins, ciliary neurotrophic factor and brain-derived neurotrophic factor, are approaches that have shown some promise, but which have also highlighted possible concerns. Manipulation of central peptidergic systems poses a number of therapeutic problems, including brain access and side effects. Given that the homeostatic defence of body weight may limit the effectiveness of any single-target therapy developed, a combination therapy approach may offer the best hope for the effective prevention and treatment of obesity. LINKED ARTICLES This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7 PMID:23121386

  1. The Evolution and Variety of RFamide-Type Neuropeptides: Insights from Deuterostomian Invertebrates

    PubMed Central

    Elphick, Maurice R.; Mirabeau, Olivier

    2014-01-01

    Five families of neuropeptides that have a C-terminal RFamide motif have been identified in vertebrates: (1) gonadotropin-inhibitory hormone (GnIH), (2) neuropeptide FF (NPFF), (3) pyroglutamylated RFamide peptide (QRFP), (4) prolactin-releasing peptide (PrRP), and (5) Kisspeptin. Experimental demonstration of neuropeptide–receptor pairings combined with comprehensive analysis of genomic and/or transcriptomic sequence data indicate that, with the exception of the deuterostomian PrRP system, the evolutionary origins of these neuropeptides can be traced back to the common ancestor of bilaterians. Here, we review the occurrence of homologs of vertebrate RFamide-type neuropeptides and their receptors in deuterostomian invertebrates – urochordates, cephalochordates, hemichordates, and echinoderms. Extending analysis of the occurrence of the RFamide motif in other bilaterian neuropeptide families reveals RFamide-type peptides that have acquired modified C-terminal characteristics in the vertebrate lineage (e.g., NPY/NPF), neuropeptide families where the RFamide motif is unique to protostomian members (e.g., CCK/sulfakinins), and RFamide-type peptides that have been lost in the vertebrate lineage (e.g., luqins). Furthermore, the RFamide motif is also a feature of neuropeptide families with a more restricted phylogenetic distribution (e.g., the prototypical FMRFamide-related neuropeptides in protostomes). Thus, the RFamide motif is both an ancient and a convergent feature of neuropeptides, with conservation, acquisition, or loss of this motif occurring in different branches of the animal kingdom. PMID:24994999

  2. Kaon-nucleus scattering

    NASA Technical Reports Server (NTRS)

    Hong, Byungsik; Maung, Khin Maung; Wilson, John W.; Buck, Warren W.

    1989-01-01

    The derivations of the Lippmann-Schwinger equation and Watson multiple scattering are given. A simple optical potential is found to be the first term of that series. The number density distribution models of the nucleus, harmonic well, and Woods-Saxon are used without t-matrix taken from the scattering experiments. The parameterized two-body inputs, which are kaon-nucleon total cross sections, elastic slope parameters, and the ratio of the real to the imaginary part of the forward elastic scattering amplitude, are presented. The eikonal approximation was chosen as our solution method to estimate the total and absorptive cross sections for the kaon-nucleus scattering.

  3. Convergence of the nucleus-nucleus Glauber multiple scattering series

    SciTech Connect

    Usmani, A.A.; Ahmad, I. )

    1991-05-01

    The Glauber {ital S}-matrix operator for nucleus-nucleus scattering is expressed as a finite series of matrix elements involving Bell's polynomials. Analyzing {alpha}{sup 4}He elastic-scattering data at the incident momentum of 4.32 GeV/{ital c}, we infer that our expansion is appreciably converging. Further, by applying closure over target and projectile states and neglecting a certain class of terms involving intermediate excitations, we arrive at a recurrence relation for nucleus-nucleus multiple scattering series terms, which invites further study as it seems to provide a simple method for calculating the nucleus-nucleus elastic-scattering cross section.

  4. Nucleus Course in Japanese.

    ERIC Educational Resources Information Center

    Akiyama, Nobuo; Flamm, Carol S.

    The "Nucleus Course in Japanese," based on the Institute of Modern Languages'"Situational Reinforcement" approach, is designed for 80 to 100 hours of instruction. Each lesson has several sections--Response drills, Appropriate Response Sequence, and Reading. Most of the lessons also include optional sections with Sentences for Repetition or a…

  5. Cell nucleus in context

    SciTech Connect

    Lelievre, Sophie A.; Bissell, Mina J.; Pujuguet, Philippe

    1999-11-11

    The molecular pathways that participate in regulation of gene expression are being progressively unraveled. Extracellular signals, including the binding of extracellular matrix and soluble molecules to cell membrane receptors, activate specific signal transducers that convey information inside the cell and can alter gene products. Some of these transducers when translocated to the cell nucleus may bind to transcription complexes and thereby modify the transcriptional activity of specific genes. However, the basic molecules involved in the regulation of gene expression are found in many different cell and tissue types; thus the mechanisms underlying tissue-specific gene expression are still obscure. In this review, we focus on the study of signals that are conveyed to the nucleus. We propose that the way in which extracellular signals are integrated may account for tissue-specific gene expression. We argue that the integration of signals depends on the structural organization of cells ( i.e., extracellular matrix, cell membrane, cytoskeleton, nucleus) which a particular cell type within a tissue. Putting the nuclei in context allows us to envision gene expression as being regulated not only by the communication between the extracellular environment and the nucleus, but also by the influence of organized assemblies of cells on extracellular-nuclear communications.

  6. Neuropeptide Y (NPY) and peptide YY (PYY) receptors in rat brain

    SciTech Connect

    Ohkubo, T.; Niwa, M.; Yamashita, K.; Kataoka, Y.; Shigematsu, K. )

    1990-12-01

    1. Specific binding sites for neuropeptide Y (NPY) and peptide YY (PYY) were investigated in rat brain areas using quantitative receptor autoradiography with {sup 125}I-Bolton-Hunter NPY ({sup 125}I-BH-NPY) and {sup 125}I-PYY, radioligands for PP-fold family peptides receptors. 2. There were no differences between localization of {sup 125}I-BH-NPY and {sup 125}I-PYY binding sites in the rat brain. High densities of the binding sites were present in the anterior olfactory nucleus, lateral septal nucleus, stratum radiatum of the hippocampus, posteromedial cortical amygdaloid nucleus, and area postrema. 3. In cold ligand-saturation experiments done in the presence of increasing concentrations of unlabeled NPY and PYY, {sup 125}I-BH-NPY and {sup 125}I-PYY binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, molecular layer of the cerebellum, and area postrema was single and of a high affinity. There was a significant difference between the affinities of {sup 125}I-BH-NPY (Kd = 0.96 nM) and {sup 125}I-PYY binding (Kd = 0.05 nM) to the molecular layer of the cerebellum. The binding of the two radioligands to the other areas examined had the same affinities. 4. When comparing the potency of unlabeled rat pancreatic polypeptide (rPP), a family peptide of NPY and PYY, to inhibit the binding to the areas examined, rPP displaced {sup 125}I-BH-NPY and {sup 125}I-PYY binding to the area postrema more potently than it did the binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, and molecular layer of the cerebellum. 5. Thus, the quantitative receptor autoradiographic method with {sup 125}I-BH-NPY and {sup 125}I-PYY revealed differences in binding characteristics of specific NPY and PYY binding sites in different areas of the rat brain. The results provide further evidence for the existence of multiple NPY-PYY receptors in the central nervous system.

  7. Onset of deconfinement in nucleus-nucleus collisions

    SciTech Connect

    Gazdzicki, M.; Gorenstein, M. I.; Seyboth, P.

    2012-05-15

    The energy dependence of hadron production in relativistic nucleus-nucleus collisions reveals anomalies-the kink, horn, and step. They were predicted as signals of the deconfinement phase transition and observed by the NA49 Collaboration in central PbPb collisions at the CERN SPS. This indicates the onset of the deconfinement in nucleus-nucleus collisions at about 30 A GeV.

  8. Spontaneous development of arcuate single-sided subduction in global 3-D mantle convection models with a free surface

    NASA Astrophysics Data System (ADS)

    Crameri, Fabio; Tackley, Paul J.

    2014-07-01

    We present temporally evolving 3-D global mantle convection models with single-sided subduction and a free surface in both 3-D Cartesian and fully spherical geometry. Special focus is given to the spontaneous development of three-dimensional structures at the surface and in the upper mantle. We find that an arcuate shape is the natural form for trenches and slabs. Cartesian models are used first to study the dynamic evolution of subduction zones, spreading ridges, and interconnected transform features. These experiments highlight the strong variation of spontaneously developing, arcuate slab curvature and subduction polarity along the trench strike. The spontaneous development of spreading ridges leads to lateral offsets between separated segments that are characterized by normal transform motion. Spherical models then allow insights into the evolution of plate tectonics on a sphere. Investigated are the spontaneous evolution of slab geometry, trench motion, and subduction-induced mantle flow. Two new dynamical features are discovered: "back-slab spiral flow" and "slab tunneling." 2014. American Geophysical Union. All Rights Reserved.

  9. The Role of Neuropeptides in Mouse Models of Colitis.

    PubMed

    Padua, David; Vu, John P; Germano, Patrizia M; Pisegna, Joseph R

    2016-06-01

    Inflammatory bowel disease (IBD) constitutes an important clinically significant condition that results in morbidity and mortality. IBD can be generally classified into either ulcerative colitis (UC) or Crohn's disease (CD) that differs in the clinical and histopathology. The role of neuropeptides in the pathogenesis of these conditions is becoming increasingly recognized for their importance in modulating the inflammatory state. Animal models provide the greatest insight to better understand the pathophysiology of both disorders which will hopefully allow for improved treatment strategies. This review will provide a better understanding of the role of murine models for studying colitis. PMID:26646243

  10. CGRP as a neuropeptide in migraine: lessons from mice

    PubMed Central

    Russo, Andrew F

    2015-01-01

    Migraine is a neurological disorder that is far more than just a bad headache. A hallmark of migraine is altered sensory perception. A likely contributor to this altered perception is the neuropeptide calcitonin gene-related peptide (CGRP). Over the past decade, CGRP has become firmly established as a key player in migraine. Although the mechanisms and sites of action by which CGRP might trigger migraine remain speculative, recent advances with mouse models provide some hints. This brief review focuses on how CGRP might act as both a central and peripheral neuromodulator to contribute to the migraine-like symptom of light aversive behaviour in mice. PMID:26032833

  11. Neuropeptide Y directly affects ovarian cell proliferation and apoptosis.

    PubMed

    Sirotkin, Alexander V; Kardošová, Diana; Alwasel, Saleh Hamad; Harrath, Abdel Halim

    2015-12-01

    The effects of neuropeptide Y (NPY; 0, 10, 100 and 1000 ng/mL) on the expression of PCNA, bax and p53 were examined by immunocytochemistry in porcine luteinized granulosa cells. NPY inhibited proliferation as well as promoted apoptosis and accumulation of p53 in the cells. This is the first report to demonstrate the direct action of NPY on ovarian cell proliferation and apoptosis. The results of the study suggest that the effect is mediated by transcription factor p53. PMID:26679167

  12. Proton Nucleus Elastic Scattering Data.

    Energy Science and Technology Software Center (ESTSC)

    1993-08-18

    Version 00 The Proton Nucleus Elastic Scattering Data file PNESD contains the numerical data and the related bibliography for the differential elastic cross sections, polarization and integral nonelastic cross sections for elastic proton-nucleus scattering.

  13. Vesicle capture, not delivery, scales up neuropeptide storage in neuroendocrine terminals

    PubMed Central

    Bulgari, Dinara; Zhou, Chaoming; Hewes, Randall S.; Deitcher, David L.; Levitan, Edwin S.

    2014-01-01

    Neurons vary in their capacity to produce, store, and release neuropeptides packaged in dense-core vesicles (DCVs). Specifically, neurons used for cotransmission have terminals that contain few DCVs and many small synaptic vesicles, whereas neuroendocrine neuron terminals contain many DCVs. Although the mechanistic basis for presynaptic variation is unknown, past research demonstrated transcriptional control of neuropeptide synthesis suggesting that supply from the soma limits presynaptic neuropeptide accumulation. Here neuropeptide release is shown to scale with presynaptic neuropeptide stores in identified Drosophila cotransmitting and neuroendocrine terminals. However, the dramatic difference in DCV number in these terminals occurs with similar anterograde axonal transport and DCV half-lives. Thus, differences in presynaptic neuropeptide stores are not explained by DCV delivery from the soma or turnover. Instead, greater neuropeptide accumulation in neuroendocrine terminals is promoted by dramatically more efficient presynaptic DCV capture. Greater capture comes with tradeoffs, however, as fewer uncaptured DCVs are available to populate distal boutons and replenish neuropeptide stores following release. Finally, expression of the Dimmed transcription factor in cotransmitting neurons increases presynaptic DCV capture. Therefore, DCV capture in the terminal is genetically controlled and determines neuron-specific variation in peptidergic function. PMID:24550480

  14. Reproductive neuropeptides that stimulate spawning in the Sydney Rock Oyster (Saccostrea glomerata).

    PubMed

    In, Vu Van; Ntalamagka, Nikoleta; O'Connor, Wayne; Wang, Tianfang; Powell, Daniel; Cummins, Scott F; Elizur, Abigail

    2016-08-01

    The Sydney Rock Oyster, Saccostrea glomerata, is a socioeconomically important species in Australia, yet little is known about the molecular mechanism that regulates its reproduction. To address this gap, we have performed a combination of high throughput transcriptomic and peptidomic analysis, to identify genes and neuropeptides that are expressed in the key regulatory tissues of S. glomerata; the visceral ganglia and gonads. Neuropeptides are known to encompass a diverse class of peptide messengers that play functional roles in many aspects of an animal's life, including reproduction. Approximately 28 neuropeptide genes were identified, primarily within the visceral ganglia transcriptome, that encode precursor proteins containing numerous neuropeptides; some were confirmed through mass spectral peptidomics analysis of the visceral ganglia. Of those, 28 bioactive neuropeptides were synthesized, and then tested for their capacity to induce gonad development and spawning in S. glomerata. Egg laying hormone, gonadotropin-releasing hormone, APGWamide, buccalin, CCAP and LFRFamide were neuropeptides found to trigger spawning in ripe animals. Additional testing of APGWa and buccalin demonstrated their capacity to advance conditioning and gonadal maturation. In summary, our analysis of S. glomerata has identified neuropeptides that can influence the reproductive cycle of this species, specifically by accelerating gonadal maturation and triggering spawning. Other molluscan neuropeptides identified in this study will enable further research into understanding the neuroendocrinology of oysters, which may benefit their cultivation. PMID:27328253

  15. Biostable analogs of insect kinin and insectatachykinin neuropeptides: Novel antifeedants and aphicides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neuropeptides are potent regulators of critical life processes in insects, but are subject to rapid degradation by peptidases in the hemolymph (blood), tissues and gut. This limitation can be overcome via replacement of peptidase susceptible portions of the insect neuropeptides with non-natural resi...

  16. Properties of VIP+ synapses in the suprachiasmatic nucleus highlight their role in circadian rhythm.

    PubMed

    Achilly, Nathan P

    2016-06-01

    Circadian rhythms coordinate cyclical behavioral and physiological changes in most organisms. In humans, this biological clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus and consists of a heterogeneous neuron population characterized by their enriched expression of various neuropeptides. As highlighted here, Fan et al. (J Neurosci 35: 1905-1029, 2015) developed an elegant experimental system to investigate the synaptic properties of vasoactive intestinal peptide (VIP)-expressing neurons between day and night, and further delineate their broader architecture and function within the SCN. PMID:26581865

  17. Diurnal fluctuations in HPA and neuropeptide Y-ergic systems underlie differences in vulnerability to traumatic stress responses at different zeitgeber times.

    PubMed

    Cohen, Shlomi; Vainer, Ella; Matar, Michael A; Kozlovsky, Nitsan; Kaplan, Zeev; Zohar, Joseph; Mathé, Aleksander A; Cohen, Hagit

    2015-02-01

    The hypothalamic-pituitary-adrenal (HPA) axis displays a characteristic circadian pattern of corticosterone release, with higher levels at the onset of the active phase and lower levels at the onset of the inactive phase. As corticosterone levels modify the response to stress and influence the susceptibility to and/or severity of stress-related sequelae, we examined the effects of an acute psychological trauma applied at different zeitgeber times (ZTs) on behavioral stress responses. Rats were exposed to stress either at the onset of the inactive-(light) phase (ZT=0) or at the onset of the active-(dark) phase (ZT=12). Their behavior in the elevated plus-maze and acoustic startle response paradigms were assessed 7 days post exposure for retrospective classification into behavioral response groups. Serum corticosterone levels and the dexamethasone suppression test were used to assess the stress response and feedback inhibition of the HPA axis. Immunoreactivity for neuropeptide Y (NPY) and NPY-Y1 receptor (Y1R) in the paraventricular (PVN) and arcuate (ARC) hypothalamic nuclei, hippocampus, and basolateral amygdala were measured. The behavioral effects of NPY/Y1R antagonist microinfused into the PVN 30 min before stress exposure during the inactive or active phase, respectively, were evaluated. PVN immunoreactivity for NPY and Y1R was measured 1 day after the behavioral tests. The time of day of the traumatic exposure markedly affected the pattern of the behavioral stress response and the prevalence of rats showing an extreme behavioral response. Rats exposed to the stressor at the onset of their inactive phase displayed a more traumatic behavioral response, faster post-exposure corticosterone decay, and a more pronounced stress-induced decline in NPY and Y1R expression in the PVN and arcuate hypothalamic nuclei. Blocking PVN Y1R before stress applied in the active phase, or administering NPY to the PVN before stress applied in the inactive phase, had a resounding

  18. Diurnal Fluctuations in HPA and Neuropeptide Y-ergic Systems Underlie Differences in Vulnerability to Traumatic Stress Responses at Different Zeitgeber Times

    PubMed Central

    Cohen, Shlomi; Vainer, Ella; Matar, Michael A; Kozlovsky, Nitsan; Kaplan, Zeev; Zohar, Joseph; Mathé, Aleksander A; Cohen, Hagit

    2015-01-01

    The hypothalamic–pituitary–adrenal (HPA) axis displays a characteristic circadian pattern of corticosterone release, with higher levels at the onset of the active phase and lower levels at the onset of the inactive phase. As corticosterone levels modify the response to stress and influence the susceptibility to and/or severity of stress-related sequelae, we examined the effects of an acute psychological trauma applied at different zeitgeber times (ZTs) on behavioral stress responses. Rats were exposed to stress either at the onset of the inactive-(light) phase (ZT=0) or at the onset of the active-(dark) phase (ZT=12). Their behavior in the elevated plus-maze and acoustic startle response paradigms were assessed 7 days post exposure for retrospective classification into behavioral response groups. Serum corticosterone levels and the dexamethasone suppression test were used to assess the stress response and feedback inhibition of the HPA axis. Immunoreactivity for neuropeptide Y (NPY) and NPY-Y1 receptor (Y1R) in the paraventricular (PVN) and arcuate (ARC) hypothalamic nuclei, hippocampus, and basolateral amygdala were measured. The behavioral effects of NPY/Y1R antagonist microinfused into the PVN 30 min before stress exposure during the inactive or active phase, respectively, were evaluated. PVN immunoreactivity for NPY and Y1R was measured 1 day after the behavioral tests. The time of day of the traumatic exposure markedly affected the pattern of the behavioral stress response and the prevalence of rats showing an extreme behavioral response. Rats exposed to the stressor at the onset of their inactive phase displayed a more traumatic behavioral response, faster post-exposure corticosterone decay, and a more pronounced stress-induced decline in NPY and Y1R expression in the PVN and arcuate hypothalamic nuclei. Blocking PVN Y1R before stress applied in the active phase, or administering NPY to the PVN before stress applied in the inactive phase, had a

  19. Short neuropeptide F is a sleep-promoting inhibitory modulator

    PubMed Central

    Shang, Yuhua; Donelson, Nathan C.; Vecsey, Christopher G.; Guo, Fang; Rosbash, Michael; Griffith, Leslie C.

    2013-01-01

    SUMMARY To advance the understanding of sleep regulation, we screened for sleep-promoting cells and identified neurons expressing neuropeptide Y-like short neuropeptide F (sNPF). Sleep-induction by sNPF meets all relevant criteria. Rebound sleep following sleep deprivation is reduced by activation of sNPF neurons and flies even experience negative sleep rebound upon cessation of sNPF neuronal stimulation, indicating that sNPF provides an important signal to the sleep homeostat. Only a subset of sNPF-expressing neurons, which includes the small ventrolateral clock neurons, is sleep-promoting. Their release of sNPF increases sleep consolidation in part by suppressing the activity of wake-promoting large ventrolateral clock neurons, and suppression of neuronal firing may be the general response to sNPF receptor activation. sNPF acutely increases sleep without altering feeding behavior, which it affects only on a much longer time scale. The profound effect of sNPF on sleep indicates that it is an important sleep-promoting molecule. PMID:24094110

  20. Allatotropin: An Ancestral Myotropic Neuropeptide Involved in Feeding

    PubMed Central

    Alzugaray, María Eugenia; Adami, Mariana Laura; Diambra, Luis Anibal; Hernandez-Martinez, Salvador; Damborenea, Cristina; Noriega, Fernando Gabriel; Ronderos, Jorge Rafael

    2013-01-01

    Background Cell-cell interactions are a basic principle for the organization of tissues and organs allowing them to perform integrated functions and to organize themselves spatially and temporally. Peptidic molecules secreted by neurons and epithelial cells play fundamental roles in cell-cell interactions, acting as local neuromodulators, neurohormones, as well as endocrine and paracrine messengers. Allatotropin (AT) is a neuropeptide originally described as a regulator of Juvenile Hormone synthesis, which plays multiple neural, endocrine and myoactive roles in insects and other organisms. Methods A combination of immunohistochemistry using AT-antibodies and AT-Qdot nanocrystal conjugates was used to identify immunoreactive nerve cells containing the peptide and epithelial-muscular cells targeted by AT in Hydra plagiodesmica. Physiological assays using AT and AT- antibodies revealed that while AT stimulated the extrusion of the hypostome in a dose-response fashion in starved hydroids, the activity of hypostome in hydroids challenged with food was blocked by treatments with different doses of AT-antibodies. Conclusions AT antibodies immunolabeled nerve cells in the stalk, pedal disc, tentacles and hypostome. AT-Qdot conjugates recognized epithelial-muscular cell in the same tissues, suggesting the existence of anatomical and functional relationships between these two cell populations. Physiological assays indicated that the AT-like peptide is facilitating food ingestion. Significance Immunochemical, physiological and bioinformatics evidence advocates that AT is an ancestral neuropeptide involved in myoregulatory activities associated with meal ingestion and digestion. PMID:24143240

  1. Neuropeptides and peptide hormones in syncope and orthostatic intolerance.

    PubMed

    Krishnan, Balaji; Benditt, David G

    2014-01-01

    Syncope and orthostatic intolerance (OI) are common clinical syndromes often requiring medical attention. The former is defined as transient loss of consciousness and postural tone due to self-limited cerebral hypoperfusion, while the latter consists of inappropriate cardiovascular responses to upright posture such as occur with orthostatic hypotension (OH) or postural orthostatic tachycardia syndrome. The most frequent causes of syncope and OI are conditions that temporarily disrupt essential moment-to-moment interaction between the autonomic nervous system and cardiovascular system. In this regard, many neuropeptides (NPs) or peptide hormones (PH) exert cardioactive effects that might contribute to the pathophysiology of certain forms of syncope or OI. To date, the principal peptides that have been studied in this context are: atrial and B-type-neuropeptides, adrenomedullin, endothelin-1 (ET-1), galanin, and vasopressin. While definitive conclusions cannot yet be drawn, the intrinsic vasoconstrictor ET-1 appears to be elevated in OH, presumably to compensate for vasodilation and hypotension of other etiologies. As such elevated ET-1 may become a marker for OH. Further, elevated NT-proBNP may play a role in causing vasodilation and hypotension in some forms of OH of previously unknown cause, and may be a marker in other patients of a cardiovascular cause of syncope and OI. In the end, the study of the role of NPs and PHs in syncope and OI syndromes is at an early stage, and considerable further future effort is needed. PMID:25299506

  2. Polymorphic variation as a driver of differential neuropeptide gene expression.

    PubMed

    Quinn, John P; Warburton, Alix; Myers, Paul; Savage, Abigail L; Bubb, Vivien J

    2013-12-01

    The regulation of neuropeptide gene expression and their receptors in a tissue specific and stimulus inducible manner will determine in part behaviour and physiology. This can be a dynamic process resulting from short term changes in response to the environment or long term modulation imposed by epigenetically determined mechanisms established during life experiences. The latter underpins what is termed 'nature and nurture, or 'gene×environment interactions'. Dynamic gene expression of neuropeptides or their receptors is a key component of signalling in the CNS and their inappropriate regulation is therefore a predicted target underpinning psychiatric disorders and neuropathological processes. Finding the regulatory domains within our genome which have the potential to direct gene expression is a difficult challenge as 98% of our genome is non-coding and, with the exception of proximal promoter regions, such elements can be quite distant from the gene that they regulate. This review will deal with how we can find such domains by addressing both the most conserved non-exonic regions in the genome using comparative genomics and the most recent or constantly evolving DNA such as repetitive DNA or retrotransposons. We shall also explore how polymorphic changes in such domains can be associated with CNS disorders by altering the appropriate gene expression patterns which maintain normal physiology. PMID:24210140

  3. Neuropeptide Y is an angiogenic factor in cardiovascular regeneration.

    PubMed

    Saraf, Rabya; Mahmood, Feroze; Amir, Rabia; Matyal, Robina

    2016-04-01

    In diabetic cardiomyopathy, there is altered angiogenic signaling and increased oxidative stress. As a result, anti-angiogenic and pro-inflammatory pathways are activated. These disrupt cellular metabolism and cause fibrosis and apoptosis, leading to pathological remodeling. The autonomic nervous system and neurotransmitters play an important role in angiogenesis. Therapies that promote angiogenesis may be able to relieve the pathology in these disease states. Neuropeptide Y (NPY) is the most abundantly produced and expressed neuropeptide in the central and peripheral nervous systems in mammals and plays an important role in promoting angiogenesis and cardiomyocyte remodeling. It produces effects through G-protein-coupled Y receptors that are widely distributed and also present on the myocardium. Some of these receptors are also involved in diseased states of the heart. NPY has been implicated as a potent growth factor, causing cell proliferation in multiple systems while the NPY3-36 fragment is selective in stimulating angiogenesis and cardiomyocyte remodeling. Current research is focusing on developing a drug delivery mechanism for NPY to prolong therapy without having significant systemic consequences. This could be a promising innovation in the treatment of diabetic cardiomyopathy and ischemic heart disease. PMID:26875634

  4. Inflammation and Neuropeptides: The Connection in Diabetic Wound Healing

    PubMed Central

    Pradhan, Leena; Nabzdyk, Christoph; Andersen, Nicholas D; LoGerfo, Frank W; Veves, Aristidis

    2013-01-01

    This article provides a broad overview of the interaction between neuropeptides and inflammatory mediators as it pertains to diabetic wound healing. Abnormal wound healing is a major complication of both type I and type II diabetes and is the most frequent cause of non-traumatic lower limb amputation. Wound healing requires the orchestrated integration of complex biological and molecular events. Inflammation, proliferation and migration of cells followed by angiogenesis and re-epithelization are essential phases of wound healing. The link between wound healing and the nervous system is clinically apparent as peripheral neuropathy is reported in 30–50% of diabetic patients and is the most common and sensitive predictor of foot ulceration. The bidirectional connection between the nervous and the immune systems and the role it plays in wound healing has emerged as one of the focal features of the wound healing dogma. The mediators of this connection include neuropeptides and the cytokines released from different cells including immune and cutaneous cells. Therefore, to develop successful wound healing therapies, it is vital to understand in depth the signaling pathways in the neuro-immune axis and their implication in diabetic wound healing. PMID:19138453

  5. Neuropeptides Modulate Female Chemosensory Processing upon Mating in Drosophila

    PubMed Central

    Zhang, Mo; Loschek, Laura F.; Grunwald Kadow, Ilona C.

    2016-01-01

    A female’s reproductive state influences her perception of odors and tastes along with her changed behavioral state and physiological needs. The mechanism that modulates chemosensory processing, however, remains largely elusive. Using Drosophila, we have identified a behavioral, neuronal, and genetic mechanism that adapts the senses of smell and taste, the major modalities for food quality perception, to the physiological needs of a gravid female. Pungent smelling polyamines, such as putrescine and spermidine, are essential for cell proliferation, reproduction, and embryonic development in all animals. A polyamine-rich diet increases reproductive success in many species, including flies. Using a combination of behavioral analysis and in vivo physiology, we show that polyamine attraction is modulated in gravid females through a G-protein coupled receptor, the sex peptide receptor (SPR), and its neuropeptide ligands, MIPs (myoinhibitory peptides), which act directly in the polyamine-detecting olfactory and taste neurons. This modulation is triggered by an increase of SPR expression in chemosensory neurons, which is sufficient to convert virgin to mated female olfactory choice behavior. Together, our data show that neuropeptide-mediated modulation of peripheral chemosensory neurons increases a gravid female’s preference for important nutrients, thereby ensuring optimal conditions for her growing progeny. PMID:27145127

  6. Neuropeptides Modulate Female Chemosensory Processing upon Mating in Drosophila.

    PubMed

    Hussain, Ashiq; Üçpunar, Habibe K; Zhang, Mo; Loschek, Laura F; Grunwald Kadow, Ilona C

    2016-05-01

    A female's reproductive state influences her perception of odors and tastes along with her changed behavioral state and physiological needs. The mechanism that modulates chemosensory processing, however, remains largely elusive. Using Drosophila, we have identified a behavioral, neuronal, and genetic mechanism that adapts the senses of smell and taste, the major modalities for food quality perception, to the physiological needs of a gravid female. Pungent smelling polyamines, such as putrescine and spermidine, are essential for cell proliferation, reproduction, and embryonic development in all animals. A polyamine-rich diet increases reproductive success in many species, including flies. Using a combination of behavioral analysis and in vivo physiology, we show that polyamine attraction is modulated in gravid females through a G-protein coupled receptor, the sex peptide receptor (SPR), and its neuropeptide ligands, MIPs (myoinhibitory peptides), which act directly in the polyamine-detecting olfactory and taste neurons. This modulation is triggered by an increase of SPR expression in chemosensory neurons, which is sufficient to convert virgin to mated female olfactory choice behavior. Together, our data show that neuropeptide-mediated modulation of peripheral chemosensory neurons increases a gravid female's preference for important nutrients, thereby ensuring optimal conditions for her growing progeny. PMID:27145127

  7. Neuropeptide FF receptors as novel targets for limbic seizure attenuation.

    PubMed

    Portelli, Jeanelle; Meurs, Alfred; Bihel, Frederic; Hammoud, Hassan; Schmitt, Martine; De Kock, Joery; Utard, Valerie; Humbert, Jean-Paul; Bertin, Isabelle; Buffel, Ine; Coppens, Jessica; Tourwe, Dirk; Maes, Veronique; De Prins, An; Vanhaecke, Tamara; Massie, Ann; Balasubramaniam, Ambikaipakan; Boon, Paul; Bourguignon, Jean-Jacques; Simonin, Frederic; Smolders, Ilse

    2015-08-01

    Neuropeptide Y (NPY) is a well established anticonvulsant and first-in-class antiepileptic neuropeptide. In this study, the controversial role of NPY1 receptors in epilepsy was reassessed by testing two highly selective NPY1 receptor ligands and a mixed NPY1/NPFF receptor antagonist BIBP3226 in a rat model for limbic seizures. While BIBP3226 significantly attenuated the pilocarpine-induced seizures, neither of the highly selective NPY1 receptor ligands altered the seizure severity. Administration of the NPFF1/NPFF2 receptor antagonist RF9 also significantly attenuated limbic seizure activity. To further prove the involvement of NPFF receptors in these seizure-modulating effects, low and high affinity antagonists for the NPFF receptors were tested. We observed that the low affinity ligand failed to exhibit anticonvulsant properties while the two high affinity ligands significantly attenuated the seizures. Continuous NPFF1 receptor agonist administration also inhibited limbic seizures whereas bolus administration of the NPFF1 receptor agonist was without effect. This suggests that continuous agonist perfusion could result in NPFF1 receptor desensitization and mimic NPFF1 receptor antagonist administration. Our data unveil for the first time the involvement of the NPFF system in the management of limbic seizures. PMID:25963417

  8. Evidence for the involvement of neuropeptide Y in the antidepressant effect of imipramine in type 2 diabetes.

    PubMed

    Nakhate, Kartik T; Yedke, Sadanand U; Bharne, Ashish P; Subhedar, Nishikant K; Kokare, Dadasaheb M

    2016-09-01

    Depression is a major comorbidity factor of diabetes and the outcome of one disorder influences the other. Our aim is to scrutinize the link between the two, if any. Since neuropeptide Y (NPY) system plays an important role in regulating central glucose sensing mechanisms, and also depression-related behavior, we test the involvement of NPY in the modulation of depression in type 2 diabetic mice. The mice were fed on high-fat diet and administered with low dose of streptozotocin to induce type 2 diabetes. These animals showed augmented plasma glucose and increased immobility time in tail suspension test (TST) suggesting induction of diabetes and depression. Intracerebroventricular (icv) treatment with NPY or NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY and intraperitoneal treatment with imipramine decreased immobility time. However, opposite effect was produced by NPY Y1 receptor antagonist BIBP3226 (icv). Moreover, reduced immobility time by imipramine was potentiated by NPY and [Leu(31), Pro(34)]-NPY, but attenuated by BIBP3226. Immunohistochemical analysis of the different nuclei of the extended amygdala, the region primarily involved in affective disorders, was undertaken. A significant reduction in NPY immunoreactivity in the central nucleus of amygdala, nucleus accumbens shell and lateral division of bed nucleus of stria terminalis of the diabetic mice was noticed; the response was ameliorated in imipramine treated animals. The results suggest that decreased NPY expression in the extended amygdala might be causally linked with the depression induced following type 2 diabetes and that the antidepressant action of imipramine in diabetic mice might be mediated by NPY-NPY Y1 receptor system. PMID:27208493

  9. Neuropeptide Y inhibits the trigeminovascular pathway through NPY Y1 receptor: implications for migraine

    PubMed Central

    Oliveira, Margarida-Martins; Akerman, Simon; Tavares, Isaura; Goadsby, Peter J.

    2016-01-01

    Abstract Migraine is a painful neurologic disorder with premonitory symptomatology that can include disturbed appetite. Migraine pathophysiology involves abnormal activation of trigeminocervical complex (TCC) neurons. Neuropeptide Y (NPY) is synthesized in the brain and is involved in pain modulation. NPY receptors are present in trigeminal ganglia and trigeminal nucleus caudalis suggesting a role in migraine pathophysiology. The present study aimed to determine the effect of systemic administration of NPY on TCC neuronal activity in response to dural nociceptive trigeminovascular activation. We performed in vivo electrophysiology in anesthetized rats, administered NPY (10, 30, and 100 µg·kg−1), and investigated the receptors involved by studying NPY Y1 (30 µg·kg−1), Y2 (30 µg·kg−1), and Y5 receptor agonists (100·µg·kg−1), and NPY Y1 receptor antagonist (30 µg·kg−1). NPY (30 and 100 µg·kg−1) significantly reduced TCC neuronal firing in response to dural-evoked trigeminovascular activation, but only NPY (30 µg·kg−1) significantly reduced spontaneous trigeminal firing. NPY Y1 receptor agonist also significantly reduced dural-evoked and spontaneous TCC neuronal firing. NPY (10 µg·kg−1), NPY Y2, and Y5 receptor agonists, and the NPY Y1 receptor antagonist had no significant effects on nociceptive dural-evoked neuronal firing in the TCC or spontaneous trigeminal firing. This study demonstrates that NPY dose dependently inhibits dural-evoked trigeminal activity, through NPY Y1 receptor activation, indicating antinociceptive actions of NPY in a migraine animal model. Based on the role of NPY in appetite regulation, it is possible that disruption of the NPY system might explain changes of appetite in migraineurs. PMID:27023421

  10. Topography and time course of changes in spinal neuropeptide Y immunoreactivity after spared nerve injury.

    PubMed

    Intondi, A B; Zadina, J E; Zhang, X; Taylor, B K

    2010-02-01

    We used a new computer-assisted method to precisely localize and efficiently quantify increases in neuropeptide Y immunoreactivity (NPY-ir) along the mediolateral axis of the L4 dorsal horn (DH) following transection of either the tibial and common peroneal nerves (thus sparing the sural branch, spared nerve injury (SNI)), the tibial nerve, or the common peroneal and sural nerves. Two weeks after SNI, NPY-ir increased within the tibial and peroneal innervation territories; however, NPY-ir in the central-lateral region (innervated by the spared sural nerve) was indistinguishable from that of sham. Conversely, transection of the sural and common peroneal nerves induced an increase in NPY-ir in the central-lateral region, while leaving the medial region (innervated by the tibial nerve) unaffected. All nerve injuries increased NPY-ir in dorsal root ganglia (DRG) and nucleus gracilis (NG). By 24 weeks, both NPY-ir upregulation in the DH and hyper-responsivity to cold and noxious mechanical stimuli had resolved. Conversely, NPY-ir in DRG and NG, and hypersensitivity to non-noxious static mechanical stimuli, did not resolve within 24 weeks. Over this time course, the average cross-sectional area of NPY-immunoreactive DRG neurons increased by 151 mum(2). We conclude that the upregulation of NPY after SNI is restricted to medial zones of the DH, and therefore cannot act directly upon synapses within the more lateral (sural) zones to control sural nerve hypersensitivity. Instead, we suggest that NPY in the medial DH tonically inhibits hypersensitivity by interrupting mechanisms of central sensitization and integration of sensory signals at the spinal and supraspinal levels. PMID:19879928

  11. Exploring the role of neuropeptide S in the regulation of arousal: a functional anatomical study.

    PubMed

    Adori, Csaba; Barde, Swapnali; Vas, Szilvia; Ebner, Karl; Su, Jie; Svensson, Camilla; Mathé, Aleksander A; Singewald, Nicolas; Reinscheid, Rainer R; Uhlén, Mathias; Kultima, Kim; Bagdy, György; Hökfelt, Tomas

    2016-09-01

    Neuropeptide S (NPS) is a regulatory peptide expressed by limited number of neurons in the brainstem. The simultaneous anxiolytic and arousal-promoting effect of NPS suggests an involvement in mood control and vigilance, making the NPS-NPS receptor system an interesting potential drug target. Here we examined, in detail, the distribution of NPS-immunoreactive (IR) fiber arborizations in brain regions of rat known to be involved in the regulation of sleep and arousal. Such nerve terminals were frequently apposed to GABAergic/galaninergic neurons in the ventro-lateral preoptic area (VLPO) and to tyrosine hydroxylase-IR neurons in all hypothalamic/thalamic dopamine cell groups. Then we applied the single platform-on-water (mainly REM) sleep deprivation method to study the functional role of NPS in the regulation of arousal. Of the three pontine NPS cell clusters, the NPS transcript levels were increased only in the peri-coerulear group in sleep-deprived animals, but not in stress controls. The density of NPS-IR fibers was significantly decreased in the median preoptic nucleus-VLPO region after the sleep deprivation, while radioimmunoassay and mass spectrometry measurements showed a parallel increase of NPS in the anterior hypothalamus. The expression of the NPS receptor was, however, not altered in the VLPO-region. The present results suggest a selective activation of one of the three NPS-expressing neuron clusters as well as release of NPS in distinct forebrain regions after sleep deprivation. Taken together, our results emphasize a role of the peri-coerulear cluster in the modulation of arousal, and the importance of preoptic area for the action of NPS on arousal and sleep. PMID:26462664

  12. Phase shifts to light are altered by antagonists to neuropeptide receptors.

    PubMed

    Chan, Ryan K; Sterniczuk, Roxanne; Enkhbold, Yaruuna; Jeffers, Ryan T; Basu, Priyoneel; Duong, Bryan; Chow, Sue-Len; Smith, Victoria M; Antle, Michael C

    2016-07-01

    The mammalian circadian clock in the suprachiasmatic nucleus (SCN) is a heterogeneous structure. Two key populations of cells that receive retinal input and are believed to participate in circadian responses to light are cells that contain vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP). VIP acts primarily through the VPAC2 receptor, while GRP works primarily through the BB2 receptor. Both VIP and GRP phase shift the circadian clock in a manner similar to light when applied to the SCN, both in vivo and in vitro, indicating that they are sufficient to elicit photic-like phase shifts. However, it is not known if they are necessary signals for light to elicit phase shifts. Here we test the hypothesis that GRP and VIP are necessary signaling components for the photic phase shifting of the hamster circadian clock by examining two antagonists for each of these neuropeptides. The BB2 antagonist PD176252 had no effect on light-induced delays on its own, while the BB2 antagonist RC-3095 had the unexpected effect of significantly potentiating both phase delays and advances. Neither of the VIP antagonists ([d-p-Cl-Phe6, Leu17]-VIP, or PG99-465) altered phase shifting responses to light on their own. When the BB2 antagonist PD176252 and the VPAC2 antagonist PG99-465 were delivered together to the SCN, phase delays were significantly attenuated. These results indicate that photic phase shifting requires participation of either VIP or GRP; phase shifts to light are only impaired when signalling in both pathways are inhibited. Additionally, the unexpected potentiation of light-induced phase shifts by RC-3095 should be investigated further for potential chronobiotic applications. PMID:27090819

  13. Neuropeptide Y inhibits the trigeminovascular pathway through NPY Y1 receptor: implications for migraine.

    PubMed

    Oliveira, Margarida-Martins; Akerman, Simon; Tavares, Isaura; Goadsby, Peter J

    2016-08-01

    Migraine is a painful neurologic disorder with premonitory symptomatology that can include disturbed appetite. Migraine pathophysiology involves abnormal activation of trigeminocervical complex (TCC) neurons. Neuropeptide Y (NPY) is synthesized in the brain and is involved in pain modulation. NPY receptors are present in trigeminal ganglia and trigeminal nucleus caudalis suggesting a role in migraine pathophysiology. The present study aimed to determine the effect of systemic administration of NPY on TCC neuronal activity in response to dural nociceptive trigeminovascular activation. We performed in vivo electrophysiology in anesthetized rats, administered NPY (10, 30, and 100 µg·kg), and investigated the receptors involved by studying NPY Y1 (30 µg·kg), Y2 (30 µg·kg), and Y5 receptor agonists (100·µg·kg), and NPY Y1 receptor antagonist (30 µg·kg). NPY (30 and 100 µg·kg) significantly reduced TCC neuronal firing in response to dural-evoked trigeminovascular activation, but only NPY (30 µg·kg) significantly reduced spontaneous trigeminal firing. NPY Y1 receptor agonist also significantly reduced dural-evoked and spontaneous TCC neuronal firing. NPY (10 µg·kg), NPY Y2, and Y5 receptor agonists, and the NPY Y1 receptor antagonist had no significant effects on nociceptive dural-evoked neuronal firing in the TCC or spontaneous trigeminal firing. This study demonstrates that NPY dose dependently inhibits dural-evoked trigeminal activity, through NPY Y1 receptor activation, indicating antinociceptive actions of NPY in a migraine animal model. Based on the role of NPY in appetite regulation, it is possible that disruption of the NPY system might explain changes of appetite in migraineurs. PMID:27023421

  14. Neuropeptide Y input to the rat basolateral amygdala complex and modulation by conditioned fear.

    PubMed

    Leitermann, Randy J; Rostkowski, Amanda B; Urban, Janice H

    2016-08-15

    Within the basolateral amygdaloid complex (BLA), neuropeptide Y (NPY) buffers against protracted anxiety and fear. Although the importance of NPY's actions in the BLA is well documented, little is known about the source(s) of NPY fibers to this region. The current studies identified sources of NPY projections to the BLA by using a combination of anatomical and neurochemical approaches. NPY innervation of the BLA was assessed in rats by examining the degree of NPY coexpression within interneurons or catecholaminergic fibers with somatostatin and tyrosine hydroxylase (TH) or dopamine β-hydroxylase (DβH), respectively. Numerous NPY(+) /somatostatin(+) and NPY(+) /somatostatin(-) fibers were observed, suggesting at least two populations of NPY fibers within the BLA. No colocalization was noted between NPY and TH or DβH immunoreactivities. Additionally, Fluorogold (FG) retrograde tracing with immunohistochemistry was used to identify the precise origin of NPY projections to the BLA. FG(+) /NPY(+) cells were identified within the amygdalostriatal transition area (AStr) and stria terminalis and scattered throughout the bed nucleus of the stria terminalis. The subpopulation of NPY neurons in the AStr also coexpressed somatostatin. Subjecting animals to a conditioned fear paradigm increased NPY gene expression within the AStr, whereas no changes were observed within the BLA or stria terminalis. Overall, these studies identified limbic regions associated with stress circuits providing NPY input to the BLA and demonstrated that a unique NPY projection from the AStr may participate in the regulation of conditioned fear. J. Comp. Neurol. 524:2418-2439, 2016. © 2016 Wiley Periodicals, Inc. PMID:26779765

  15. Analytic optical potentials for nucleon-nucleus nucleus-nucleus collisions involving light and medium nuclei

    NASA Technical Reports Server (NTRS)

    Bidasaria, H. B.; Townsend, L. W.

    1982-01-01

    Utilizing an optical model potential approximation to the exact nucleus-nucleus multiple-scattering series, optical potentials for nucleon-nucleus and nucleus-nucleus collisions are analytically derived. These expressions are applicable to light and medium cosmic ray nuclei as their single-particle density distributions are analytically determined, without approximation, from their actual harmonic well charge density distributions. Pauli correlation effects are included through the use of a simple Gaussian function to replace the usual expression obtained in the infinite nuclear matter approximation.

  16. A case of pancreatic cancer with concomitant median arcuate ligament syndrome treated successfully using an allograft arterial transposition

    PubMed Central

    Celik, Sebahattin; Ringe, Kristina I.; Boru, Cristian E.; Constantinica, Victor; Bektas, Hüseyin

    2015-01-01

    An association of pancreatic cancer and median arcuate ligament syndrome (MALS) is a rare and challenging situation in terms of treatment. A 60-year-old man diagnosed with pancreatic cancer underwent laparotomy. A pancreaticoduodenectomy was planned, but during the resection part of the operation, a celiac artery stenosis was noticed. The patient was diagnosed with MALS causing almost total celiac artery occlusion, with no radiological solution. The patient was re-operated the next day, and an iliac artery allograft was used for aorta-proper hepatic artery reconstruction, concomitant with the total pancreaticoduodenectomy. Preoperative meticulous evaluation of vascular structures of the celiac trunk and its branches is important, especially in pancreatic surgery. A vascular allograft may be a lifesaving alternative when vascular reconstruction is necessary. PMID:26715412

  17. Nucleus from string theory

    NASA Astrophysics Data System (ADS)

    Hashimoto, Koji; Morita, Takeshi

    2011-08-01

    In generic holographic QCD, we find that baryons are bound to form a nucleus, and that its radius obeys the empirically-known mass-number (A) dependence r∝A1/3 for large A. Our result is robust, since we use only a generic property of D-brane actions in string theory. We also show that nucleons are bound completely in a finite volume. Furthermore, employing a concrete holographic model (derived by Hashimoto, Iizuka, and Yi, describing a multibaryon system in the Sakai-Sugimoto model), the nuclear radius is evaluated as O(1)×A1/3[fm], which is consistent with experiments.

  18. Neutrino-nucleus interactions

    SciTech Connect

    Gallagher, H.; Garvey, G.; Zeller, G.P.; /Fermilab

    2011-01-01

    The study of neutrino oscillations has necessitated a new generation of neutrino experiments that are exploring neutrino-nuclear scattering processes. We focus in particular on charged-current quasi-elastic scattering, a particularly important channel that has been extensively investigated both in the bubble-chamber era and by current experiments. Recent results have led to theoretical reexamination of this process. We review the standard picture of quasi-elastic scattering as developed in electron scattering, review and discuss experimental results, and discuss additional nuclear effects such as exchange currents and short-range correlations that may play a significant role in neutrino-nucleus scattering.

  19. Immunoreactive intensity of FXPRL amide neuropeptides in response to environmental conditions in the silkworm, Bombyx mori.

    PubMed

    Hagino, Ayako; Kitagawa, Norio; Imai, Kunio; Yamashita, Okitsugu; Shiomi, Kunihiro

    2010-12-01

    In the silkworm Bombyx mori, the diapause hormone-pheromone biosynthesis activating neuropeptide gene, DH-PBAN, is a neuropeptide gene that encodes a polypeptide precursor consisting in five Phe-X-Pro-Arg-Leu-NH(2) (FXPRL) amide (FXPRLa) neuropeptides; DH (diapause hormone), PBAN (pheromone-biosynthesis-activating neuropeptide) and α-, β- and γ-SGNPs (subesophageal ganglion neuropeptides). These neuropeptides are synthesized in DH-PBAN-producing neurosecretory cells contained within three neuromeres, four mandibular cells, six maxillary cells, two labial cells (SLb) and four lateral cells of the subesophageal ganglion. DH is solely responsible, among the FXPRLa peptide family, for embryonic diapause. Functional differentiation has been previously suggested to occur at each neuromere, with the SLb cells releasing DH through brain innervation in order to induce embryonic diapause. We have investigated the immunoreactive intensity of DH in the SLb when thermal (25°C or 15°C) and light (continuous illumination or darkness) conditions are altered and following brain surgery that induces diapause or non-diapause eggs in the progeny. We have also examined the immunoreactivity of the other FXPRLa peptides by using anti-β-SGNP and anti-PBAN antibodies. Pupal SLb somata immunoreactivities seem to be affected by both thermal and light conditions during embryogenesis. Thus, we have been able to identify a close correlation between the immunoreactive intensity of neuropeptides and environmental conditions relating to the determination of embryonic diapause in B. mori. PMID:21103995

  20. Evolutionary conservation of neuropeptide expression in the thymus of different species

    PubMed Central

    Silva, Alberto B; Aw, Danielle; Palmer, Donald B

    2006-01-01

    Evidence suggests that the immune and neuroendocrine systems cross talk by sharing ligands and receptors. Hormones and neuropeptides produced by the neuroendocrine system often modulate the function of lymphoid organs and immune cells. We have previously reported the intrathymic expression of somatostatin (SOM) in the mouse and that several neuropeptides, most notably calcitonin-gene-related peptide (CGRP), neuropeptide Y (NPY), SOM and substance P (SP), can modulate thymocyte development. However, little is known about the intrathymic expression of these neuropeptides either in the mouse or in other species. Moreover, a comparative analysis of the expression of these molecules would highlight the evolutionary importance of intrathymic neuroendocrine interactions in T-cell development. We have studied the expression of different neuropeptides in the thymus of zebrafish, Xenopus, avians, rodent, porcine, equine and human by immunohistochemistry and reverse transcription–polymerase chain reaction. We found that CGRP, NPY, SOM, SP and vasointestinal polypeptide (VIP) are expressed in the thymus of all species investigated. The thymic location of many of these neuropeptides was conserved and appears to be within the stromal compartments. Interestingly, in the avian thymus the expression of CGRP, SOM and SP appears to change depending on the age of the tissue. These findings suggest that neuropeptides may play an important role in T-cell development and provide further evidence of cross talk between the immune and neuroendocrine systems. PMID:16630030

  1. Decoding the superior parietal lobule connections of the superior longitudinal fasciculus/arcuate fasciculus in the human brain.

    PubMed

    Kamali, A; Sair, H I; Radmanesh, A; Hasan, K M

    2014-09-26

    The temporo-parietal (TP) white matter connections between the inferior parietal lobule and superior temporal gyrus as part of the superior longitudinal fasciculus/arcuate fasciculus (SLF/AF) or middle longitudinal fasciculus (MdLF) have been studied in prior diffusion tensor tractography (DTT) studies. However, few studies have been focusing on the higher TP connections of the superior parietal lobule with the temporal lobe. These higher TP connections have been shown to have a role in core processes such as attention, memory, emotions, and language. Our most recent study, for the first time, hinted to the possibility of a long white matter connection interconnecting the superior parietal lobule (SPL) with the posterior temporal lobe in human brain which we call the SLF/AF TP-SPL and for a shorter abbreviation, the TP-SPL. We decided to further investigate this white matter connection using fiber assignment by continuous tracking deterministic tractography and high spatial resolution diffusion tensor imaging on 3T. Five healthy right-handed men (age range 24-37 years) were studied. We delineated the SPL connections of the SLF/AF TP bilaterally in five normal adult human brains. Using a high resolution DTT technique, we demonstrate for the first time, the trajectory of a long fiber bundle connectivity between the SPL and posterior temporal lobe, called the SLF/AF TP-SPL (or the TP-SPL), bilaterally in five healthy adult human brains. We also demonstrate the trajectory of the vertically oriented posterior TP connections, interconnecting the inferior parietal lobule (IPL) with the posterior temporal lobe (TP-IPL) in relation to the TP-SPL, arcuate fasciculus and other major language pathways. In the current study, for the first time, we categorized the TP connections into the anterior and posterior connectivity groups and subcategorized each one into the SPL or IPL connections. PMID:25086308

  2. More than two decades of research on insect neuropeptide GPCRs: an overview

    PubMed Central

    Caers, Jelle; Verlinden, Heleen; Zels, Sven; Vandersmissen, Hans Peter; Vuerinckx, Kristel; Schoofs, Liliane

    2012-01-01

    This review focuses on the state of the art on neuropeptide receptors in insects. Most of these receptors are G protein-coupled receptors (GPCRs) and are involved in the regulation of virtually all physiological processes during an insect's life. More than 20 years ago a milestone in invertebrate endocrinology was achieved with the characterization of the first insect neuropeptide receptor, i.e., the Drosophila tachykinin-like receptor. However, it took until the release of the Drosophila genome in 2000 that research on neuropeptide receptors boosted. In the last decade a plethora of genomic information of other insect species also became available, leading to a better insight in the functions and evolution of the neuropeptide signaling systems and their intracellular pathways. It became clear that some of these systems are conserved among all insect species, indicating that they fulfill crucial roles in their physiological processes. Meanwhile, other signaling systems seem to be lost in several insect orders or species, suggesting that their actions were superfluous in those insects, or that other neuropeptides have taken over their functions. It is striking that the deorphanization of neuropeptide GPCRs gets much attention, but the subsequent unraveling of the intracellular pathways they elicit, or their physiological functions are often hardly examined. Especially in insects besides Drosophila this information is scarce if not absent. And although great progress made in characterizing neuropeptide signaling systems, even in Drosophila several predicted neuropeptide receptors remain orphan, awaiting for their endogenous ligand to be determined. The present review gives a précis of the insect neuropeptide receptor research of the last two decades. But it has to be emphasized that the work done so far is only the tip of the iceberg and our comprehensive understanding of these important signaling systems will still increase substantially in the coming years. PMID

  3. Neuropeptide Y bioavailability is suppressed in the hindlimb of female Sprague-Dawley rats

    PubMed Central

    Jackson, Dwayne N; Milne, Kevin J; Noble, Earl G; Shoemaker, J Kevin

    2005-01-01

    We recently reported that male, but not female, rats exhibit basal endogenous neuropeptide Y Y1-receptor modulation of hindlimb vasculature. The lack of baseline endo-genous Y1-receptor control in females was evident despite the expression of Y1-receptors and neuropeptide Y in hindlimb skeletal muscle tissue. The following study addressed the hypothesis that neuropeptide Y bioavailability is blunted in female rats under baseline conditions. It was further hypothesized that enhanced prejunctional autoinhibitory neuropeptide Y Y2-receptor expression and/or proteolytic processing of released neuropeptide Y may persist in female rats. Using western blot analysis, it was observed that females had greater overall neuropeptide Y Y2-receptor expression in skeletal muscle compared to males (P < 0.05). To address the prevalence/impact of baseline endogenous Y2-receptor activation on neuropeptide Y release in hindlimb vasculature, an arterial infusion of BIIE0246 (specific non-peptide Y2-receptor antagonist; 170 μg kg−1) was carried out on female and male rats. Y2-receptor blockade resulted in a decrease in hindlimb vascular conductance in females and males (P < 0.05). However, the BIIE0246-induced decrease in vascular conductance was Y1-receptor dependent in females, but not males (P < 0.05). In addition, compared to baseline, BIIE0246 infusion resulted in increased plasma neuropeptide Y concentration in females (P < 0.05), while there was no observable change in males. In a final experiment, systemic inhibition of proteolytic enzymes dipeptidylpeptidase IV (via 500 nm diprotin A) and aminopeptidase P (via 180 nm 2-mercaptoethanol) elicited a Y1-receptor-dependent decrease in hindlimb vascular conductance in females (P < 0.05). It was concluded that our previously reported lack of basal endogenous Y1-receptor activation in female hindlimb vasculature was (at least partially) due to prejunctional Y2-receptor autoinhibition and proteolytic processing of neuropeptide Y. PMID

  4. Higgs-Boson Production in Nucleus-Nucleus Collisions

    NASA Technical Reports Server (NTRS)

    Norbury, John W.

    1992-01-01

    Cross section calculations are presented for the production of intermediate-mass Higgs bosons produced in ultrarelativistic nucleus-nucleus collisions via two photon fusion. The calculations are performed in position space using Baur's method for folding together the Weizsacker-Williams virtual-photon spectra of the two colliding nuclei. It is found that two photon fusion in nucleus-nucleus collisions is a plausible way of finding intermediate-mass Higgs bosons at the Superconducting Super Collider or the CERN Large Hadron Collider.

  5. Higgs-boson production in nucleus-nucleus collisions

    NASA Technical Reports Server (NTRS)

    Norbury, J. W.; Townsend, L. W. (Principal Investigator)

    1990-01-01

    Cross-section calculations are presented for the production of intermediate-mass Higgs bosons produced in ultrarelativistic nucleus-nucleus collisions via two-photon fusion. The calculations are performed in position space using Baur's method for folding together the Weizsacker-Williams virtual-photon spectra of the two colliding nuclei. It is found that two-photon fusion in nucleus-nucleus collisions is a plausible way of finding intermediate-mass Higgs bosons at the Superconducting Super Collider or the CERN Large Hadron Collider.

  6. Estrogens and Neuropeptides in Postmenopausal Women: Un Update

    PubMed Central

    Guida, M.; Zullo, F.; Buonomo, B.; Marra, M.L.; Palatucci, V.; Pascale, R.; Visconti, F.; Guerra, G.; Spinelli, ML; Di Spiezio Sardo, A.

    2012-01-01

    Summary Menopause is characterized by depletion of ovarian follicles, a reduction of ovarian hormones to castrate levels and elevated levels of serum gonadotropins from the anterior pituitary gland. Although this process has significant repercussions throughout the body and affects a large proportion of our society, the neuroendocrine control mechanisms that accompany menopause are poorly understood. This review aims to examine rigorously the most accredited literature to provide an update about our current understanding of the role of the hypothalamic-pituitary axis in the onset of and transition into female reproductive senescence, focusing on the role of some specific neuropeptides in regulating the HPG axis and on their effects on several menopausal symptoms, especially referring to the cardiovascular risk, to open up new horizons for new therapeutic strategies. PMID:23905050

  7. Neuropeptide Y receptors in rat brain: autoradiographic localization

    SciTech Connect

    Martel, J.C.; St-Pierre, S.; Quirion, R.

    1986-01-01

    Neuropeptide Y (NPY) receptor binding sites have been characterized in rat brain using both membrane preparations and receptor autoradiography. Radiolabelled NPY binds with high affinity and specificity to an apparent single class of sites in rat brain membrane preparations. The ligand selectivity pattern reveals strong similarities between central and peripheral NPY receptors. NPY receptors are discretely distributed in rat brain with high densities found in the olfactory bulb, superficial layers of the cortex, ventral hippocampus, lateral septum, various thalamic nuclei and area postrema. The presence of high densities of NPY and NPY receptors in such areas suggests that NPY could serve important functions as a major neurotransmitter/neuromodulator in the central nervous system.

  8. The effect of obesogenic diets on brain Neuropeptide Y.

    PubMed

    Gumbs, Myrtille C R; van den Heuvel, José K; la Fleur, Susanne E

    2016-08-01

    Obesity is a major health problem characterized by accumulated fat mass. The availability of an energy-dense, highly palatable diet plays an important role in obesity development. Neuropeptide Y (NPY), an orexigenic peptide, is affected by dietary composition and NPY can affect dietary preference. The hypothalamic NPY system is well characterized and has been studied in several models of obesity. However, findings from models of diet-induced obesity are not straightforward. In addition, NPY plays a role in (food-)motivated behaviors and interacts with the mesolimbic dopamine system, both of which are altered in obesity. We here review the effect of obesogenic diets on NPY levels in the hypothalamus and reward-related regions. PMID:27132202

  9. Sociality, pathogen avoidance, and the neuropeptides oxytocin and arginine vasopressin.

    PubMed

    Kavaliers, Martin; Choleris, Elena

    2011-11-01

    Both humans and nonhumans have evolved a variety of mechanisms to recognize pathogen threat and a variety of adaptive behavioral responses to minimize exposure to it. Because social interactions facilitate the spread of infection among individuals, the ability to recognize and avoid infected and potentially infected individuals is crucial. The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) are involved in mediating various facets of social behavior, including social recognition and responses to salient social threats. Results of studies with rodents have revealed that OT and AVP are also associated with the olfactory-mediated recognition and avoidance of actually or potentially infected individuals. The evidence reviewed here suggests that OT and AVP likely play parallel roles in modulating the recognition and avoidance of socially relevant pathogen threat in both humans and rodents. PMID:21960250

  10. Salusin-β as a powerful endogenous antidipsogenic neuropeptide

    PubMed Central

    Suzuki-Kemuriyama, Noriko; Nakano-Tateno, Tae; Tani, Yuji; Hirata, Yukio; Shichiri, Masayoshi

    2016-01-01

    Salusin-β is an endogenous parasympathomimetic peptide, predominantly localized to the hypothalamus and posterior pituitary. Subcutaneously administered salusin-β (50 nmol/mouse) significantly increased water intake but did not affect locomotor activity or food intake. The salusin-β-induced increase in water intake was completely abrogated by pretreatment with muscarinic antagonist, atropine sulphate. In contrast, intracerebroventricular injection of salusin-β, at lower doses (10–100 fmol/mouse) caused a long-lasting decrease in water intake and locomotor activity throughout the entire dark phase of the diurnal cycle. Pre-injection of intracerebroventricular anti-salusin-β IgG completely abrogated the central salusin-β mediated suppression of water intake and locomotor activity. These results demonstrate contrasting actions of salusin-β in the control of water intake via the central and peripheral systems and highlight it as a potent endogenous antidipsogenic neuropeptide. PMID:26869388

  11. Networking the nucleus

    PubMed Central

    Rajapakse, Indika; Scalzo, David; Tapscott, Stephen J; Kosak, Steven T; Groudine, Mark

    2010-01-01

    The nuclei of differentiating cells exhibit several fundamental principles of self-organization. They are composed of many dynamical units connected physically and functionally to each other—a complex network—and the different parts of the system are mutually adapted and produce a characteristic end state. A unique cell-specific signature emerges over time from complex interactions among constituent elements that delineate coordinate gene expression and chromosome topology. Each element itself consists of many interacting components, all dynamical in nature. Self-organizing systems can be simplified while retaining complex information using approaches that examine the relationship between elements, such as spatial relationships and transcriptional information. These relationships can be represented using well-defined networks. We hypothesize that during the process of differentiation, networks within the cell nucleus rewire according to simple rules, from which a higher level of order emerges. Studying the interaction within and among networks provides a useful framework for investigating the complex organization and dynamic function of the nucleus. PMID:20664641

  12. Cloning, expression and processing of the CP2 neuropeptide precursor of Aplysia.

    PubMed

    Vilim, F S; Alexeeva, V; Moroz, L L; Li, L; Moroz, T P; Sweedler, J V; Weiss, K R

    2001-12-01

    The cDNA sequence encoding the CP2 neuropeptide precursor is identified and encodes a single copy of the neuropeptide that is flanked by appropriate processing sites. The distribution of the CP2 precursor mRNA is described and matches the CP2-like immunoreactivity described previously. Single cell RT-PCR independently confirms the presence of CP2 precursor mRNA in selected neurons. MALDI-TOF MS is used to identify additional peptides derived from the CP2 precursor in neuronal somata and nerves, suggesting that the CP2 precursor may give rise to additional bioactive neuropeptides. PMID:11786187

  13. Platelet neuropeptide Y is critical for ischemic revascularization in mice

    PubMed Central

    Tilan, Jason U.; Everhart, Lindsay M.; Abe, Ken; Kuo-Bonde, Lydia; Chalothorn, Dan; Kitlinska, Joanna; Burnett, Mary Susan; Epstein, Stephen E.; Faber, James E.; Zukowska, Zofia

    2013-01-01

    We previously reported that the sympathetic neurotransmitter neuropeptide Y (NPY) is potently angiogenic, primarily through its Y2 receptor, and that endogenous NPY is crucial for capillary angiogenesis in rodent hindlimb ischemia. Here we sought to identify the source of NPY responsible for revascularization and its mechanisms of action. At d 3, NPY−/− mice demonstrated delayed recovery of blood flow and limb function, consistent with impaired collateral conductance, while ischemic capillary angiogenesis was reduced (∼70%) at d 14. This biphasic temporal response was confirmed by 2 peaks of NPY activation in rats: a transient early increase in neuronally derived plasma NPY and increase in platelet NPY during late-phase recovery. Compared to NPY-null platelets, collagen-activated NPY-rich platelets were more mitogenic (∼2-fold vs. ∼1.6-fold increase) for human microvascular endothelial cells, and Y2/Y5 receptor antagonists ablated this difference in proliferation. In NPY+/+ mice, ischemic angiogenesis was prevented by platelet depletion and then restored by transfusion of platelets from NPY+/+ mice, but not NPY−/− mice. In thrombocytopenic NPY−/− mice, transfusion of wild-type platelets fully restored ischemia-induced angiogenesis. These findings suggest that neuronally derived NPY accelerates the early response to femoral artery ligation by promoting collateral conductance, while platelet-derived NPY is critical for sustained capillary angiogenesis.—Tilan, J. U., Everhart, L. M., Abe, K., Kuo-Bonde, L., Chalothorn, D., Kitlinska, J., Burnett, M. S., Epstein, S. E., Faber, J. E., Zukowska, Z. Platelet neuropeptide Y is critical for ischemic revascularization in mice. PMID:23457218

  14. Electric quadrupole excitations in relativistic nucleus-nucleus collisions

    NASA Technical Reports Server (NTRS)

    Norbury, John W.

    1989-01-01

    Calculations are presented for electric quadrupole excitations in relativistic nucleus-nucleus collisions. The theoretical results are compared to an extensive data set and it is found that electric quadrupole effects provide substantial corrections to cross sections, especially for heavier nuclei.

  15. Meson multiplicity versus energy in relativistic nucleus-nucleus collisions

    NASA Technical Reports Server (NTRS)

    Atwater, T. W.; Freier, P. S.

    1986-01-01

    A systematic study of meson multiplicity as a function of energy at energies up to 100 GeV/u in nucleus-nucleus collisions has been made, using cosmic-ray data in nuclear emulsion. The data are consistent with simple nucleon-nucleon superposition models. Multiplicity per interacting nucleon in AA collisions does not appear to differ significantly from pp collisions.

  16. Scaling phenomenon in relativistic nucleus-nucleus collisions

    SciTech Connect

    Wong, C. Y.; Blankenbecler, R.

    1980-01-01

    New scaling variables for proton and pion production in relativistic nucleus-nucleus collisions are introduced which are the generalizations of the Feynmann scaling variable. They allow a simple description of the cross sections at forward and backward angles. 2 figures.

  17. Momentum loss in proton-nucleus and nucleus-nucleus collisions

    NASA Technical Reports Server (NTRS)

    Khan, Ferdous; Townsend, Lawrence W.

    1993-01-01

    An optical model description, based on multiple scattering theory, of longitudinal momentum loss in proton-nucleus and nucleus-nucleus collisions is presented. The crucial role of the imaginary component of the nucleon-nucleon transition matrix in accounting for longitudinal momentum transfer is demonstrated. Results obtained with this model are compared with Intranuclear Cascade (INC) calculations, as well as with predictions from Vlasov-Uehling-Uhlenbeck (VUU) and quantum molecular dynamics (QMD) simulations. Comparisons are also made with experimental data where available. These indicate that the present model is adequate to account for longitudinal momentum transfer in both proton-nucleus and nucleus-nucleus collisions over a wide range of energies.

  18. The Galactic Nucleus

    NASA Astrophysics Data System (ADS)

    Melia, Fulvio

    Exciting new broadband observations of the galactic nucleus have placed the heart of the Milky Way under intense scrutiny in recent years. This has been due in part to the growing interest from theorists motivated to study the physics of black hole accretion, magnetized gas dynamics, and unusual star formation. The center of our Galaxy is now known to harbor the most compelling supermassive black hole candidate, weighing in at 3-4 million solar masses. Its nearby environment is comprised of a molecular dusty ring, clusters of evolved and young stars, diffuse hot gas, ionized gas streamers, and several supernova remnants. This chapter will focus on the physical makeup of this dynamic region and the feasibility of actually imaging the black hole's shadow in the coming decade with mm interferometry.

  19. Spatiotemporal profiles of arginine vasopressin transcription in cultured suprachiasmatic nucleus.

    PubMed

    Yoshikawa, Tomoko; Nakajima, Yoshihiro; Yamada, Yoshiko; Enoki, Ryosuke; Watanabe, Kazuto; Yamazaki, Maya; Sakimura, Kenji; Honma, Sato; Honma, Ken-ichi

    2015-11-01

    Arginine vasopressin (AVP), a major neuropeptide in the suprachiasmatic nucleus (SCN), is postulated to mediate the output of the circadian oscillation. Mice carrying a reporter gene of AVP transcription (AVP(ELuc)) were produced by knocking-in a cDNA of Emerald-luciferase (ELuc) in the translational initiation site. Homozygous mice did not survive beyond postnatal day 7. Using the heterozygous (AVP(ELuc/+)) mice, a bioluminescence reporter system was developed that enabled to monitor AVP transcription through AVP-ELuc measurement in real time for more than 10 cycles in the cultured brain slice. AVP(ELuc/+) mice showed circadian behaviour rhythms and light responsiveness indistinguishable from those of the wild-type. Robust circadian rhythms in AVP-ELuc were detected in the cultured SCN slice at a single cell as well as tissue levels. The circadian rhythm of the whole SCN slice was stable, with the peak at the mid-light phase of a light-dark cycle, while that of a single cell was more variable. By comparison, rhythmicity in the paraventricular nucleus and supraoptic nucleus in the hypothalamus was unstable and damped rapidly. Spatiotemporal profiles of AVP expression at the pixel level revealed significant circadian rhythms in the entire area of AVP-positive cells in the SCN, and at least two clusters that showed different circadian oscillations. Contour analysis of bioluminescence intensity in a cell-like region demonstrated the radiation area was almost identical to the cell size. This newly developed reporter system for AVP gene expression is a useful tool for the study of circadian rhythms. PMID:26342201

  20. Probing Neuropeptide Signaling at the Organ and Cellular Domains via Imaging Mass Spectrometry

    PubMed Central

    Ye, Hui; Greer, Tyler; Li, Lingjun

    2012-01-01

    Imaging mass spectrometry (IMS) has evolved to be a promising technology due to its ability to detect a broad mass range of molecular species and create density maps for selected compounds. It is currently one of the most useful techniques to determine the spatial distribution of neuropeptides in cells and tissues. Although IMS is conceptually simple, sample preparation steps, mass analyzers, and software suites are just a few of the factors that contribute to the successful design of a neuropeptide IMS experiment. This review provides a brief overview of IMS sampling protocols, instrumentation, data analysis tools, technological advancements and applications to neuropeptide localization in neurons and endocrine tissues. Future perspectives in this field are also provided, concluding that neuropeptide IMS could revolutionize neuronal network and biomarker discovery studies. PMID:22465716

  1. The Endoparasitoid, Cotesia vestalis, Regulates Host Physiology by Reprogramming the Neuropeptide Transcriptional Network

    PubMed Central

    Shi, Min; Dong, Shuai; Li, Ming-tian; Yang, Yan-yan; Stanley, David; Chen, Xue-xin

    2015-01-01

    Endoparasitoids develop inside another insect by regulating host immunity and development via maternal factors injected into hosts during oviposition. Prior results have provided insights into parasitism-induced immunosuppression, including the neuropeptide accumulation in parasitized insects. Nonetheless, our understanding of neuropeptide influence on host development and behavior is not yet complete. We posed the hypothesis that parasitization alters expression of genes encoding pro-neuropeptides and used larvae of Plutella xylostella and its endoparasitoid, Cotesia vestalis to test our hypothesis. We prepared transcriptomes from the larval P. xylostella brain-CC-CA complex and identified transcripts encoding 19 neuropeptides. All corresponding cDNAs were confirmed by RACE. Our results demonstrate that parasitism significantly down-regulated, or delayed, expression of genes encoding pro-neuropeptides within 48 h post-parasitization. Changing expression of these genes may account for the previously reported decreased feeding behavior, reduced growth rates and aborted development in the host larvae. In effect, parasitization may operate at the molecular level within the CNS to create global changes in larval host biology. The significance of our finding is that, in addition to the known effects on immunity, parasitoids influence host pro-neuropeptide gene transcription. This finding reveals a new mechanism operating in host-parasitoid relationships to the advantage of the parasitoid. PMID:25640113

  2. The role of Neuropeptide Y in fear conditioning and extinction.

    PubMed

    Tasan, R O; Verma, D; Wood, J; Lach, G; Hörmer, B; de Lima, T C M; Herzog, H; Sperk, G

    2016-02-01

    While anxiety disorders are the brain disorders with the highest prevalence and constitute a major burden for society, a considerable number of affected people are still treated insufficiently. Thus, in an attempt to identify potential new anxiolytic drug targets, neuropeptides have gained considerable attention in recent years. Compared to classical neurotransmitters they often have a regionally restricted distribution and may bind to several distinct receptor subtypes. Neuropeptide Y (NPY) is a highly conserved neuropeptide that is specifically concentrated in limbic brain areas and signals via at least 5 different G-protein-coupled receptors. It is involved in a variety of physiological processes including the modulation of emotional-affective behaviors. An anxiolytic and stress-reducing property of NPY is supported by many preclinical studies. Whether NPY may also interact with processing of learned fear and fear extinction is comparatively unknown. However, this has considerable relevance since pathological, inappropriate and generalized fear expression and impaired fear extinction are hallmarks of human post-traumatic stress disorder and a major reason for its treatment-resistance. Recent evidence from different laboratories emphasizes a fear-reducing role of NPY, predominantly mediated by exogenous NPY acting on Y1 receptors. Since a reduction of fear expression was also observed in Y1 receptor knockout mice, other Y receptors may be equally important. By acting on Y2 receptors, NPY promotes fear extinction and generates a long-term suppression of fear, two important preconditions that could support cognitive behavioral therapies in human patients. A similar effect has been demonstrated for the closely related pancreatic polypeptide (PP) when acting on Y4 receptors. Preliminary evidence suggests that NPY modulates fear in particular by activation of Y1 and Y2 receptors in the basolateral and central amygdala, respectively. In the basolateral amygdala, NPY

  3. Efferent and afferent connections of the ventromedial hypothalamic nucleus determined by neural tracer analysis: implications for lordosis regulation in female rats.

    PubMed

    Shimogawa, Yuji; Sakuma, Yasuo; Yamanouchi, Korehito

    2015-02-01

    Neural connections of the ventromedial hypothalamic nucleus (VMN) to and from forebrain and midbrain structures, which are involved in the neuroendocrine regulation of reproduction, were investigated. A retrograde (fluoro-gold [FG]) or an anterograde neural tracer (phaseolus vulgaris-leucoagglutinin [PHA-L]) was injected into the left side of the VMN in ovariectomized rats. Six days after injection with FG or 11 days after injection with PHA-L, brains were fixed and sectioned. After immunohistochemistry, digital images of FG-labeled neural cell bodies (FG-cells) or PHA-L-labeled fibers (PHA-L-fibers) were analyzed. Injection sites of FG and PHA-L were mainly in the ventrolateral VMN. Considerable numbers of FG-cells and PHA-L-fibers were present in the left side of the medial amygdala, ventral lateral septum, preoptic area, bed nucleus of stria terminalis, dorsomedial hypothalamic nucleus, arcuate nucleus, periventricular nucleus of thalamus, and midbrain central gray. The lateral dorsal raphe nuclei contained many PHA-L-fibers but few FG-cells. By contrast, both sides of the median raphe nucleus contained many FG-cells but few PHA-L-fibers. Reciprocal direct neural connection between the right and left side of the VMN were observed. The present results provide an anatomical basis for functional relationships between the VMN and these nuclei. PMID:25448544

  4. Influence of ETR-p1/f1 antisense peptide on endothelin-induced constriction in rat renal arcuate arteries

    PubMed Central

    Wu, Xiaochun; Richards, Nicholas T; Johns, Edward J; Kohsaka, Takeo; Nakamura, Akio; Okada, Hidechika

    1997-01-01

    This study set out to examine the endothelin receptor subtypes mediating vasoconstriction in the rat renal arcuate artery. This was done in isolated vessels 120–200 μm in diameter, incubated with a selective agonist and the novel ‘antisense' peptide to part of the human endothelinA receptor. Groups of vessels (n=6) were incubated with increasing concentrations of endothelin-1 (ET-1), from 1 to 100 nM, which caused a 65% maximal contraction at the highest dose with an pEC50 of 8.16±0.11 M. By contrast, in six other vessels sarafotoxin 6c over the same dose range gave a minimal contraction (around 5% of maximum). Preincubation of six vessels with the antisense peptide ETR p1/f1 at 1 μM had no effect on the ET-1 induced vasoconstriction, in terms of displacement of the concentration-response curve or the maximal tension achieved by the agonist. In the six vessels exposed to 4 μM ETR p1/f1, there was a significant shift of the concentration-response curve and a lower pEC50 at 7.78±0.09 M (P<0.05). At the highest concentrations of ETR p1/f1, there was a marked suppression of all responses to ET-1, which at the maximal concentrations tested, 0.1 μM, only reached some 10% of the maximal achievable contraction. Increasing ET-1 concentrations up to 2 μM in vessels incubated with 40 μM ETR-p1/f1 showed that the blockade could be overcome and that the relationship was shifted to the right (P<0.001) by approximately one log unit with a pEC50 of 7.13±0.11 M. A Schild plot of the data indicated the antagonist to be acting competitively at a single population of receptors. At the highest concentrations tested, 40 μM, ETR-p1/f1 had no effect on noradrenaline-induced contractions, indicating a lack of non-specific actions. Together, these data suggest that at the rat renal arcuate artery the endothelinA receptor is the predominant functional receptor mediating contraction. Furthermore, this study has shown the potential usefulness of this novel

  5. Antiproton-nucleus interaction

    NASA Astrophysics Data System (ADS)

    Cugnon, J.; Vandermeulen, J.

    The antiproton-nucleus physics is reviewed. On the experimental side, the recent results obtained at the LEAR, BNL and KEK facilities are analyzed. A brief summary of the main pp and pn experimental data is also given. The antiproton-nucleus interaction can lead to elasic, inelastic and charge exchange scattering and to annihilation. The latter is very dominant. The scattering cross-sections are usually analyzed in terms of complex potential models. The relationship between potentials, charge conjugation and Dirac phenomenology is discussed. Much emphasis is put on the dynamics of the antiproton annihilation on nuclei. The energy transfer, pion absorption and target response are analyzed within the intranuclear cascade model. Special interest is devoted to strangeness production, hypernucleus formation and possible annihilation on two nucleons. Signatures for this new process are searched in experimental data. Finally, the highly debated question of quark-gluon formation is analyzed. Cet article constitue une revue de la physique antiproton-noyau. Du point de vue expérimental, cette revue porte particulièrement sur les récents résultats obtenus à LEAR, BNL et KEK. On y a aussi inclus une mise à jour des faits expérimentaux principaux pour pp et pn. L'interaction antiproton-noyau conduit à la diffusion élastique, inélastique et d'xA9change de charge et à des processus d'annihilation. Habituellement, les expériences de diffusion sont analysées en termes de potentiels complexes. La relation entre ces potentiels, la conjugaison de charge et la phénoménologie de Dirac est discutée. On s'est particulièrement intéressé à la dynamique de l'annihilation d'antiprotons sur des noyaux. Le transfert d'énergie, l'absorption de pions et la réponse de la cible sont analysés dans le cadre du modèle de cascade intranucléaire. Certains autres points sont discutés plus en détail: la production d'étrangeté, la formation d'hypernoyaux et l'annihilation sur

  6. Neuropeptide S facilitates mice olfactory function through activation of cognate receptor-expressing neurons in the olfactory cortex.

    PubMed

    Shao, Yu-Feng; Zhao, Peng; Dong, Chao-Yu; Li, Jing; Kong, Xiang-Pan; Wang, Hai-Liang; Dai, Li-Rong; Hou, Yi-Ping

    2013-01-01

    Neuropeptide S (NPS) is a newly identified neuromodulator located in the brainstem and regulates various biological functions by selectively activating the NPS receptors (NPSR). High level expression of NPSR mRNA in the olfactory cortex suggests that NPS-NPSR system might be involved in the regulation of olfactory function. The present study was undertaken to investigate the effects of intracerebroventricular (i.c.v.) injection of NPS or co-injection of NPSR antagonist on the olfactory behaviors, food intake, and c-Fos expression in olfactory cortex in mice. In addition, dual-immunofluorescence was employed to identify NPS-induced Fos immunereactive (-ir) neurons that also bear NPSR. NPS (0.1-1 nmol) i.c.v. injection significantly reduced the latency to find the buried food, and increased olfactory differentiation of different odors and the total sniffing time spent in olfactory habituation/dishabituation tasks. NPS facilitated olfactory ability most at the dose of 0.5 nmol, which could be blocked by co-injection of 40 nmol NPSR antagonist [D-Val(5)]NPS. NPS administration dose-dependently inhibited food intake in fasted mice. Ex-vivo c-Fos and NPSR immunohistochemistry in the olfactory cortex revealed that, as compared with vehicle-treated mice, NPS markedly enhanced c-Fos expression in the anterior olfactory nucleus (AON), piriform cortex (Pir), ventral tenia tecta (VTT), the anterior cortical amygdaloid nucleus (ACo) and lateral entorhinal cortex (LEnt). The percentage of Fos-ir neurons that also express NPSR were 88.5% and 98.1% in the AON and Pir, respectively. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the olfactory cortex, facilitates olfactory function in mice. PMID:23614017

  7. Mechanics of the Nucleus

    PubMed Central

    Lammerding, Jan

    2015-01-01

    The nucleus is the distinguishing feature of eukaryotic cells. Until recently, it was often considered simply as a unique compartment containing the genetic information of the cell and associated machinery, without much attention to its structure and mechanical properties. This article provides compelling examples that illustrate how specific nuclear structures are associated with important cellular functions, and how defects in nuclear mechanics can cause a multitude of human diseases. During differentiation, embryonic stem cells modify their nuclear envelope composition and chromatin structure, resulting in stiffer nuclei that reflect decreased transcriptional plasticity. In contrast, neutrophils have evolved characteristic lobulated nuclei that increase their physical plasticity, enabling passage through narrow tissue spaces in their response to inflammation. Research on diverse cell types further demonstrates how induced nuclear deformations during cellular compression or stretch can modulate cellular function. Pathological examples of disturbed nuclear mechanics include the many diseases caused by mutations in the nuclear envelope proteins lamin A/C and associated proteins, as well as cancer cells that are often characterized by abnormal nuclear morphology. In this article, we will focus on determining the functional relationship between nuclear mechanics and cellular (dys-)function, describing the molecular changes associated with physiological and pathological examples, the resulting defects in nuclear mechanics, and the effects on cellular function. New insights into the close relationship between nuclear mechanics and cellular organization and function will yield a better understanding of normal biology and will offer new clues into therapeutic approaches to the various diseases associated with defective nuclear mechanics. PMID:23737203

  8. Evolution of neuropeptide Y and its related peptides.

    PubMed

    Larhammar, D; Blomqvist, A G; Söderberg, C

    1993-11-01

    1. The neuropeptide Y (NPY) family of peptides includes also the gut endocrine peptide YY (PYY), tetrapod pancreatic polypeptide (PP), and fish pancreatic peptide-tyrosine (PY). All peptides are 36 amino acids long. 2. Sequences from many types of vertebrates show that NPY has remained extremely well conserved throughout vertebrate evolution with 92% identity between mammals and cartilaginous fishes. 3. PYY has 97-100% identity between cartilaginous fishes and bony fishes, but is less conserved in amphibians and mammals (83% identity between amphibians and sharks and 75% identity between mammals and sharks). 4. NPY and PYY share 70-80% identity in most species. 5. Both NPY and PYY were present in the early vertebrate ancestor because both peptides have been found in lampreys. 6. The tissue distribution appears to have been largely conserved between phyla, except that PYY has more widespread neuronal expression in lower vertebrates. 7. Pancreatic polypeptide has diverged considerably among tetrapods leaving only 50% identity between mammals, birds/reptiles and frogs. 8. Several lines of evidence suggest that the PP gene arose by duplication of the PYY gene, probably in the early evolution of the tetrapods. 9. The pancreatic peptide PY found in anglerfish and daddy sculpin may have resulted from an independent duplication of the PYY gene. 10. The relationships of the recently described mollusc and worm peptides NPF and PYF with the NPY family still appear unclear. PMID:7905810

  9. Ant trail pheromone biosynthesis is triggered by a neuropeptide hormone.

    PubMed

    Choi, Man-Yeon; Vander Meer, Robert K

    2012-01-01

    Our understanding of insect chemical communication including pheromone identification, synthesis, and their role in behavior has advanced tremendously over the last half-century. However, endocrine regulation of pheromone biosynthesis has progressed slowly due to the complexity of direct and/or indirect hormonal activation of the biosynthetic cascades resulting in insect pheromones. Over 20 years ago, a neurohormone, pheromone biosynthesis activating neuropeptide (PBAN) was identified that stimulated sex pheromone biosynthesis in a lepidopteran moth. Since then, the physiological role, target site, and signal transduction of PBAN has become well understood for sex pheromone biosynthesis in moths. Despite that PBAN-like peptides (∼200) have been identified from various insect Orders, their role in pheromone regulation had not expanded to the other insect groups except for Lepidoptera. Here, we report that trail pheromone biosynthesis in the Dufour's gland (DG) of the fire ant, Solenopsis invicta, is regulated by PBAN. RNAi knock down of PBAN gene (in subesophageal ganglia) or PBAN receptor gene (in DG) expression inhibited trail pheromone biosynthesis. Reduced trail pheromone was documented analytically and through a behavioral bioassay. Extension of PBAN's role in pheromone biosynthesis to a new target insect, mode of action, and behavioral function will renew research efforts on the involvement of PBAN in pheromone biosynthesis in Insecta. PMID:23226278

  10. Ant Trail Pheromone Biosynthesis Is Triggered by a Neuropeptide Hormone

    PubMed Central

    Choi, Man-Yeon; Vander Meer, Robert K.

    2012-01-01

    Our understanding of insect chemical communication including pheromone identification, synthesis, and their role in behavior has advanced tremendously over the last half-century. However, endocrine regulation of pheromone biosynthesis has progressed slowly due to the complexity of direct and/or indirect hormonal activation of the biosynthetic cascades resulting in insect pheromones. Over 20 years ago, a neurohormone, pheromone biosynthesis activating neuropeptide (PBAN) was identified that stimulated sex pheromone biosynthesis in a lepidopteran moth. Since then, the physiological role, target site, and signal transduction of PBAN has become well understood for sex pheromone biosynthesis in moths. Despite that PBAN-like peptides (∼200) have been identified from various insect Orders, their role in pheromone regulation had not expanded to the other insect groups except for Lepidoptera. Here, we report that trail pheromone biosynthesis in the Dufour's gland (DG) of the fire ant, Solenopsis invicta, is regulated by PBAN. RNAi knock down of PBAN gene (in subesophageal ganglia) or PBAN receptor gene (in DG) expression inhibited trail pheromone biosynthesis. Reduced trail pheromone was documented analytically and through a behavioral bioassay. Extension of PBAN's role in pheromone biosynthesis to a new target insect, mode of action, and behavioral function will renew research efforts on the involvement of PBAN in pheromone biosynthesis in Insecta. PMID:23226278

  11. Environmental enrichment induces behavioural disturbances in neuropeptide Y knockout mice

    PubMed Central

    Reichmann, Florian; Wegerer, Vanessa; Jain, Piyush; Mayerhofer, Raphaela; Hassan, Ahmed M.; Fröhlich, Esther E.; Bock, Elisabeth; Pritz, Elisabeth; Herzog, Herbert; Holzer, Peter; Leitinger, Gerd

    2016-01-01

    Environmental enrichment (EE) refers to the provision of a complex and stimulating housing condition which improves well-being, behaviour and brain function of laboratory animals. The mechanisms behind these beneficial effects of EE are only partially understood. In the current report, we describe a link between EE and neuropeptide Y (NPY), based on findings from NPY knockout (KO) mice exposed to EE. Relative to EE-housed wildtype (WT) animals, NPY KO mice displayed altered behaviour as well as molecular and morphological changes in amygdala and hippocampus. Exposure of WT mice to EE reduced anxiety and decreased central glucocorticoid receptor expression, effects which were absent in NPY KO mice. In addition, NPY deletion altered the preference of EE items, and EE-housed NPY KO mice responded to stress with exaggerated hyperthermia, displayed impaired spatial memory, had higher hippocampal brain-derived neurotrophic factor mRNA levels and altered hippocampal synaptic plasticity, effects which were not seen in WT mice. Accordingly, these findings suggest that NPY contributes to the anxiolytic effect of EE and that NPY deletion reverses the beneficial effects of EE into a negative experience. The NPY system could thus be a target for “enviromimetics”, therapeutics which reproduce the beneficial effects of enhanced environmental stimulation. PMID:27305846

  12. The effect of tachykinin neuropeptides on amyloid {beta} aggregation

    SciTech Connect

    Flashner, Efrat; Raviv, Uri; Friedler, Assaf

    2011-04-01

    Research highlights: {yields} Mechanistic explanation of how tachykinin neuropeptides reduce A{beta}-induced neurotoxicity. {yields} Biophysical studies suggest that tachykinins do not modulate the distribution of A{beta} oligomeric states, but rather may incorporate into the fibrils. {yields} A possible strategy to inhibit toxicity of amyloid fibrils. -- Abstract: A hallmark of Alzheimer's disease is production of amyloid {beta} peptides resulting from aberrant cleavage of the amyloid precursor protein. Amyloid {beta} assembles into fibrils under physiological conditions, through formation of neurotoxic intermediate oligomers. Tachykinin peptides are known to affect amyloid {beta} neurotoxicity in cells. To understand the mechanism of this effect, we studied how tachykinins affect A{beta}(1-40) aggregation in vitro. Fibrils grown in the presence of tachykinins exhibited reduced thioflavin T (ThT) fluorescence, while their morphology, observed in transmission electron microscopy (TEM), did not alter. Cross linking studies revealed that the distribution of low molecular weight species was not affected by tachykinins. Our results suggest that there may be a specific interaction between tachykinins and A{beta}(1-40) that allows them to co-assemble. This effect may explain the reduction of A{beta}(1-40) neurotoxicity in cells treated with tachykinins.

  13. Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond.

    PubMed

    Ciccocioppo, Roberto; Gehlert, Donald R; Ryabinin, Andrey; Kaur, Simranjit; Cippitelli, Andrea; Thorsell, Annika; Lê, Anh D; Hipskind, Philip A; Hamdouchi, Chafiq; Lu, Jianliang; Hembre, Erik J; Cramer, Jeffrey; Song, Min; McKinzie, David; Morin, Michelle; Economidou, Daina; Stopponi, Serena; Cannella, Nazzareno; Braconi, Simone; Kallupi, Marsida; de Guglielmo, Giordano; Massi, Maurizio; George, David T; Gilman, Jody; Hersh, Jacqueline; Tauscher, Johannes T; Hunt, Stephen P; Hommer, Daniel; Heilig, Markus

    2009-11-01

    This article summarizes the proceedings of a symposium held at the conference on "Alcoholism and Stress: A Framework for Future Treatment Strategies" in Volterra, Italy, May 6-9, 2008. Chaired by Markus Heilig and Roberto Ciccocioppo, this symposium offered a forum for the presentation of recent data linking neuropetidergic neurotransmission to the regulation of different alcohol-related behaviors in animals and in humans. Dr. Donald Gehlert described the development of a new corticotrophin-releasing factor receptor 1 antagonist and showed its efficacy in reducing alcohol consumption and stress-induced relapse in different animal models of alcohol abuse. Dr. Andrey Ryabinin reviewed recent findings in his laboratory, indicating a role of the urocortin 1 receptor system in the regulation of alcohol intake. Dr. Annika Thorsell showed data supporting the significance of the neuropeptide Y receptor system in the modulation of behaviors associated with a history of ethanol intoxication. Dr. Roberto Ciccocioppo focused his presentation on the nociceptin/orphanin FQ (N/OFQ) receptors as treatment targets for alcoholism. Finally, Dr. Markus Heilig showed recent preclinical and clinical evidence suggesting that neurokinin 1 antagonism may represent a promising new treatment for alcoholism. Collectively, these investigators highlighted the significance of neuropeptidergic neurotransmission in the regulation of neurobiological mechanisms of alcohol addiction. Data also revealed the importance of these systems as treatment targets for the development of new medication for alcoholism. PMID:19913192

  14. Environmental enrichment induces behavioural disturbances in neuropeptide Y knockout mice.

    PubMed

    Reichmann, Florian; Wegerer, Vanessa; Jain, Piyush; Mayerhofer, Raphaela; Hassan, Ahmed M; Fröhlich, Esther E; Bock, Elisabeth; Pritz, Elisabeth; Herzog, Herbert; Holzer, Peter; Leitinger, Gerd

    2016-01-01

    Environmental enrichment (EE) refers to the provision of a complex and stimulating housing condition which improves well-being, behaviour and brain function of laboratory animals. The mechanisms behind these beneficial effects of EE are only partially understood. In the current report, we describe a link between EE and neuropeptide Y (NPY), based on findings from NPY knockout (KO) mice exposed to EE. Relative to EE-housed wildtype (WT) animals, NPY KO mice displayed altered behaviour as well as molecular and morphological changes in amygdala and hippocampus. Exposure of WT mice to EE reduced anxiety and decreased central glucocorticoid receptor expression, effects which were absent in NPY KO mice. In addition, NPY deletion altered the preference of EE items, and EE-housed NPY KO mice responded to stress with exaggerated hyperthermia, displayed impaired spatial memory, had higher hippocampal brain-derived neurotrophic factor mRNA levels and altered hippocampal synaptic plasticity, effects which were not seen in WT mice. Accordingly, these findings suggest that NPY contributes to the anxiolytic effect of EE and that NPY deletion reverses the beneficial effects of EE into a negative experience. The NPY system could thus be a target for "enviromimetics", therapeutics which reproduce the beneficial effects of enhanced environmental stimulation. PMID:27305846

  15. Lessons learned from a case of multivessel median arcuate ligament syndrome in the setting of an Arc of Buhler.

    PubMed

    O'Brien, Kevin; Ferral, Hector

    2016-09-01

    The median arcuate ligament (MAL) can rarely compress both the celiac axis and superior mesenteric artery. We present a case of a 70-year male who presented with isolated episodes of upper abdominal pain and diarrhea associated with sweats and nausea. Angiography images demonstrated complete occlusion of the celiac axis and compression of the superior mesenteric artery during the expiration phases. The celiac axis was reconstituted distal to its origin by a patent Arc of Buhler. Other reported cases of multivessel MALs have produced severe symptoms in young adults requiring surgical and/or endovascular intervention. In this case, our patient's Arc of Buhler was protective against more severe chronic mesenteric ischemia. We suggest that a patent Arc of Buhler is protective against symptoms in a single vessel MALs patient. A significant percentage of patients receiving surgical intervention for MALs do not have relief of symptoms. There should be a search for an Arc of Buhler before surgical management of patients suspected to have single vessel MALs. PMID:27594946

  16. Relative Importance of the Arcuate and Anteroventral Periventricular Kisspeptin Neurons in Control of Puberty and Reproductive Function in Female Rats

    PubMed Central

    Hu, M. H.; Li, X. F.; McCausland, B.; Li, S. Y.; Gresham, R.; Kinsey-Jones, J. S.; Gardiner, J. V.; Sam, A. H.; Bloom, S. R.; Poston, L.; Lightman, S. L.; Murphy, K. G.

    2015-01-01

    Kisspeptin plays a critical role in pubertal timing and reproductive function. In rodents, kisspeptin perikarya within the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei are thought to be involved in LH pulse and surge generation, respectively. Using bilateral microinjections of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC or AVPV of female rats at postnatal day 10, we investigated the relative importance of these two kisspeptin populations in the control of pubertal timing, estrous cyclicity, and LH surge and pulse generation. A 37% knockdown of kisspeptin in the AVPV resulted in a significant delay in vaginal opening and first vaginal estrous, abnormal estrous cyclicity, and reduction in the occurrence of spontaneous LH surges, although these retained normal amplitude. This AVPV knockdown had no effect on LH pulse frequency, measured after ovariectomy. A 32% reduction of kisspeptin in the ARC had no effect on the onset of puberty but resulted in abnormal estrous cyclicity and decreased LH pulse frequency. Additionally, the knockdown of kisspeptin in the ARC decreased the amplitude but not the incidence of LH surges. These results might suggest that the role of AVPV kisspeptin in the control of pubertal timing is particularly sensitive to perturbation. In accordance with our previous studies, ARC kisspeptin signaling was critical for normal pulsatile LH secretion in female rats. Despite the widely reported role of AVPV kisspeptin neurons in LH surge generation, this study suggests that both AVPV and ARC populations are essential for normal LH surges and estrous cyclicity. PMID:25875299

  17. Compartmentalization of the precheliceral neuroectoderm in the spider Cupiennius salei: development of the arcuate body, optic ganglia, and mushroom body.

    PubMed

    Doeffinger, Carola; Hartenstein, Volker; Stollewerk, Angelika

    2010-07-01

    Similarly to vertebrates, arthropod brains are compartmentalized into centers with specific neurological functions such as cognition, behavior, and memory. The centers can be further subdivided into smaller functional units. This raises the question of how these compartments are formed during development and how they are integrated into brain centers. We show here for the first time how the precheliceral neuroectoderm of the spider Cupiennius salei is compartmentalized to form the distinct brain centers of the visual system: the optic ganglia, the mushroom bodies, and the arcuate body. The areas of the visual brain centers are defined by the formation of grooves and vesicles and express the proneural gene CsASH1, followed by expression of the neural differentiation marker Prospero. Furthermore, the transcription factor dachshund, which is strongly enriched in the mushroom bodies and the outer optic ganglion of Drosophila, is expressed in the optic anlagen and the mushroom bodies of the spider. The developing brain centers are further subdivided into single neural precursor groups, which become incorporated into the grooves and vesicles but remain distinguishable throughout development, suggesting that they encode spatial information for neural subtype identity. Several molecular and morphological aspects of the development of the optic ganglia and the mushroom bodies are similar in the spider and in insects. Furthermore, we show that the primary engrailed head spot contributes neurons to the optic ganglia of the median eyes, whereas the secondary head spot, which has been associated with the optic ganglia in insects and crustaceans, is absent. PMID:20503430

  18. Two Neutron Removal in Relativistic Nucleus-Nucleus Reactions

    NASA Technical Reports Server (NTRS)

    Norbury, John W.

    1992-01-01

    Significant discrepancies between theory and experiment have previously been noted for double neutron removal via electromagnetic processes in relativistic nucleus-nucleus collisions. The present work examines the cause of these discrepancies and systematically investigates whether the problem might be due to electromagnetic theory, nuclear contributions, or an underestimate of experimental error. Using cross section systematics from other reactions it is found that the discrepancies can be resolved in a plausible manner.

  19. Comparison of synganglion neuropeptides, neuropeptide receptors and neurotransmitter receptors and their gene expression in response to feeding in Ixodes scapularis (Ixodidae) vs. Ornithodoros turicata (Argasidae).

    PubMed

    Egekwu, N; Sonenshine, D E; Garman, H; Barshis, D J; Cox, N; Bissinger, B W; Zhu, J; M Roe, R

    2016-02-01

    Illumina GAII high-throughput sequencing was used to compare expressed genes for female synganglion neuropeptides, neuropeptide receptors and neurotransmitter receptors of the soft tick Ornithodoros turicata with the hard tick Ixodes scapularis. Gene ontology molecular level three mapping revealed no significant differences amongst the same categories represented in O. turicata and I. scapularis. Transcripts predicting 22 neuropeptides or their receptors in the O. turicata synganglion were similar to annotations for 23 neuropeptides or receptors previously identified from I scapularis, with minor exceptions. A transcript predicting ecdysis triggering hormone receptor was identified in O. turicata; transcripts encoding for proprotein convertase and glycoprotein B were identified in both species. Transcripts predicting the same neurotransmitter receptors were found in the synganglion of both species. Gene expression of the transcripts showed numerous differences in response to feeding. Major differences were observed in expression of genes believed important in regulating slow vs. rapid feeding, blood water elimination, cuticle synthesis plasticity and in signalling reproductive activity. Although the glutamate receptor was strongly upregulated in both species, the gamma aminobutyric acid receptor, which inhibits glutamate, was upregulated significantly only in I. scapularis. These differences are consistent with the slow vs. rapid action of the pharyngeal pump in the two species. PMID:26783017

  20. Identification and expression profiles of neuropeptides and their G protein-coupled receptors in the rice stem borer Chilo suppressalis.

    PubMed

    Xu, Gang; Gu, Gui-Xiang; Teng, Zi-Wen; Wu, Shun-Fan; Huang, Jia; Song, Qi-Sheng; Ye, Gong-Yin; Fang, Qi

    2016-01-01

    In insects, neuropeptides play important roles in the regulation of multiple physiological processes by binding to their corresponding receptors, which are primarily G protein-coupled receptors (GPCRs). The genes encoding neuropeptides and their associated GPCRs in the rice stem borer Chilo suppressalis were identified by a transcriptomic analysis and were used to identify potential targets for the disruption of physiological processes and the protection of crops. Forty-three candidate genes were found to encode the neuropeptide precursors for all known insect neuropeptides except for arginine-vasopressin-like peptide (AVLP), CNMamide, neuropeptide-like precursors 2-4 (NPLP2-4), and proctolin. In addition, novel alternative splicing variants of three neuropeptide genes (allatostatin CC, CCHamide 1, and short neuropeptide F) are reported for the first time, and 51 putative neuropeptide GPCRs were identified. Phylogenetic analyses demonstrated that 44 of these GPCRs belong to the A-family (or rhodopsin-like), 5 belong to the B-family (or secretin-like), and 2 are leucine-rich repeat-containing GPCRs. These GPCRs and their likely ligands were also described. qRT-PCR analyses revealed the expression profiles of the neuropeptide precursors and GPCR genes in various tissues of C. suppressalis. Our study provides fundamental information that may further our understanding of neuropeptidergic signaling systems in Lepidoptera and aid in the design of peptidomimetics, pseudopeptides or small molecules capable of disrupting the physiological processes regulated by these signaling molecules and their receptors. PMID:27353701

  1. Identification and expression profiles of neuropeptides and their G protein-coupled receptors in the rice stem borer Chilo suppressalis

    PubMed Central

    Xu, Gang; Gu, Gui-Xiang; Teng, Zi-Wen; Wu, Shun-Fan; Huang, Jia; Song, Qi-Sheng; Ye, Gong-Yin; Fang, Qi

    2016-01-01

    In insects, neuropeptides play important roles in the regulation of multiple physiological processes by binding to their corresponding receptors, which are primarily G protein-coupled receptors (GPCRs). The genes encoding neuropeptides and their associated GPCRs in the rice stem borer Chilo suppressalis were identified by a transcriptomic analysis and were used to identify potential targets for the disruption of physiological processes and the protection of crops. Forty-three candidate genes were found to encode the neuropeptide precursors for all known insect neuropeptides except for arginine-vasopressin-like peptide (AVLP), CNMamide, neuropeptide-like precursors 2-4 (NPLP2-4), and proctolin. In addition, novel alternative splicing variants of three neuropeptide genes (allatostatin CC, CCHamide 1, and short neuropeptide F) are reported for the first time, and 51 putative neuropeptide GPCRs were identified. Phylogenetic analyses demonstrated that 44 of these GPCRs belong to the A-family (or rhodopsin-like), 5 belong to the B-family (or secretin-like), and 2 are leucine-rich repeat-containing GPCRs. These GPCRs and their likely ligands were also described. qRT-PCR analyses revealed the expression profiles of the neuropeptide precursors and GPCR genes in various tissues of C. suppressalis. Our study provides fundamental information that may further our understanding of neuropeptidergic signaling systems in Lepidoptera and aid in the design of peptidomimetics, pseudopeptides or small molecules capable of disrupting the physiological processes regulated by these signaling molecules and their receptors. PMID:27353701

  2. Mapping of neuropeptides in the crustacean stomatogastric nervous system by imaging mass spectrometry.

    PubMed

    Ye, Hui; Hui, Limei; Kellersberger, Katherine; Li, Lingjun

    2013-01-01

    Considerable effort has been devoted to characterizing the crustacean stomatogastric nervous system (STNS) with great emphasis on comprehensive analysis and mapping distribution of its diverse neuropeptide complement. Previously, immunohistochemistry (IHC) has been applied to this endeavor, yet with identification accuracy and throughput compromised. Therefore, molecular imaging methods are pursued to unequivocally determine the identity and location of the neuropeptides at a high spatial resolution. In this work, we developed a novel, multi-faceted mass spectrometric strategy combining profiling and imaging techniques to characterize and map neuropeptides from the blue crab Callinectes sapidus STNS at the network level. In total, 55 neuropeptides from 10 families were identified from the major ganglia in the C. sapidus STNS for the first time, including the stomatogastric ganglion (STG), the paired commissural ganglia (CoG), the esophageal ganglion (OG), and the connecting nerve stomatogastric nerve (stn) using matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) and the MS/MS capability of this technique. In addition, the locations of multiple neuropeptides were documented at a spatial resolution of 25 μm in the STG and upstream nerve using MALDI-TOF/TOF and high-mass-resolution and high-mass-accuracy MALDI-Fourier transform ion cyclotron resonance (FT-ICR) instrument. Furthermore, distributions of neuropeptides in the whole C. sapidus STNS were examined by imaging mass spectrometry (IMS). Different isoforms from the same family were simultaneously and unambiguously mapped, facilitating the functional exploration of neuropeptides present in the crustacean STNS and exemplifying the revolutionary role of this novel platform in neuronal network studies. PMID:23192703

  3. Mapping of Neuropeptides in the Crustacean Stomatogastric Nervous System by Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Ye, Hui; Hui, Limei; Kellersberger, Katherine; Li, Lingjun

    2013-01-01

    Considerable effort has been devoted to characterizing the crustacean stomatogastric nervous system (STNS) with great emphasis on comprehensive analysis and mapping distribution of its diverse neuropeptide complement. Previously, immunohistochemistry (IHC) has been applied to this endeavor, yet with identification accuracy and throughput compromised. Therefore, molecular imaging methods are pursued to unequivocally determine the identity and location of the neuropeptides at a high spatial resolution. In this work, we developed a novel, multi-faceted mass spectrometric strategy combining profiling and imaging techniques to characterize and map neuropeptides from the blue crab Callinectes sapidus STNS at the network level. In total, 55 neuropeptides from 10 families were identified from the major ganglia in the C. sapidus STNS for the first time, including the stomatogastric ganglion (STG), the paired commissural ganglia (CoG), the esophageal ganglion (OG), and the connecting nerve stomatogastric nerve ( stn) using matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) and the MS/MS capability of this technique. In addition, the locations of multiple neuropeptides were documented at a spatial resolution of 25 μm in the STG and upstream nerve using MALDI-TOF/TOF and high-mass-resolution and high-mass-accuracy MALDI-Fourier transform ion cyclotron resonance (FT-ICR) instrument. Furthermore, distributions of neuropeptides in the whole C. sapidus STNS were examined by imaging mass spectrometry (IMS). Different isoforms from the same family were simultaneously and unambiguously mapped, facilitating the functional exploration of neuropeptides present in the crustacean STNS and exemplifying the revolutionary role of this novel platform in neuronal network studies.

  4. Neuropeptide B (NPB) and neuropeptide W (NPW) system in cultured rat calvarial osteoblast-like (ROB) cells: NPW and NPB inhibit proliferative activity of ROB cells.

    PubMed

    Ziolkowska, Agnieszka; Rucinski, Marcin; Tyczewska, Marianna; Malendowicz, Ludwik K

    2009-12-01

    Neuropeptides B (NPB) and W (NPW) have been identified as endogenous ligands of two G-protein-coupled receptors, neuropeptides B/W receptor 1 (NPBWR1, formerly known as GPR7) and neuropeptides B/W receptor 2 (NPBWR2, formerly known as GPR8). In rodents where NPBWR2 is absent, its counterpart is named the similar to neuropeptides B/W receptor 2 (similar to NPBWR2, formerly GPR8-like). Both NPB and NPW play a role in the control of feeding, neuroendocrine axis functions, memory and learning processes as well as in pain regulation. The present study aimed to investigate the expression of NPB, NPW, NPBWR1 and the similar to NPBWR2 genes in cultured rat calvarial osteoblast-like (ROB) cells and the effects of both peptides on proliferative activity and osteocalcin secretion by ROB cells. Classic RT-PCR technique revealed the presence of ppNPB mRNA, ppNPW mRNA, and NPBWR1 mRNA, but not similar to NPBWR2 mRNA in ROB cells. QPCR revealed gradual (days 7, 14 and 21 of culture) increase of the ppNPB gene expression, while expression of ppNPW gene was the highest at day 14 and was comparable to that seen in freshly isolated cells. In ROB cells, expression of NPBWR1 gene was notable at day 7 of culture, lower at day 21, and negligible at day 14. Neither NPB nor NPW changed osteocalcin secretion by cultured osteoblast-like cells while both neuropeptides inhibited their proliferative activity. Results of the present study suggest that the systems of NPW, NPB and NPBWR1 directly regulate proliferative activity of cultured rat calvaria osteoblast-like cells. The physiological significance of this osteoblastic system remains unclear, and requires further investigation. PMID:19885618

  5. Unexpected doubly-magic nucleus.

    SciTech Connect

    Janssens, R. V. F.; Physics

    2009-01-01

    Nuclei with a 'magic' number of both protons and neutrons, dubbed doubly magic, are particularly stable. The oxygen isotope {sup 24}O has been found to be one such nucleus - yet it lies just at the limit of stability.

  6. Select Neuropeptides and their G-Protein Coupled Receptors in Caenorhabditis Elegans and Drosophila Melanogaster

    PubMed Central

    Bendena, William G.; Campbell, Jason; Zara, Lian; Tobe, Stephen S.; Chin-Sang, Ian D.

    2012-01-01

    The G-protein coupled receptor (GPCR) family is comprised of seven transmembrane domain proteins and play important roles in nerve transmission, locomotion, proliferation and development, sensory perception, metabolism, and neuromodulation. GPCR research has been targeted by drug developers as a consequence of the wide variety of critical physiological functions regulated by this protein family. Neuropeptide GPCRs are the least characterized of the GPCR family as genetic systems to characterize their functions have lagged behind GPCR gene discovery. Drosophila melanogaster and Caenorhabditis elegans are genetic model organisms that have proved useful in characterizing neuropeptide GPCRs. The strength of a genetic approach leads to an appreciation of the behavioral plasticity that can result from subtle alterations in GPCRs or regulatory proteins in the pathways that GPCRs control. Many of these invertebrate neuropeptides, GPCRs, and signaling pathway components serve as models for mammalian counterparts as they have conserved sequences and function. This review provides an overview of the methods to match neuropeptides to their cognate receptor and a state of the art account of neuropeptide GPCRs that have been characterized in D. melanogaster and C. elegans and the behaviors that have been uncovered through genetic manipulation. PMID:22908006

  7. Multiple amidated neuropeptides are required for normal circadian locomotor rhythms in Drosophila.

    PubMed

    Taghert, P H; Hewes, R S; Park, J H; O'Brien, M A; Han, M; Peck, M E

    2001-09-01

    In Drosophila, the amidated neuropeptide pigment dispersing factor (PDF) is expressed by the ventral subset of lateral pacemaker neurons and is required for circadian locomotor rhythms. Residual rhythmicity in pdf mutants likely reflects the activity of other neurotransmitters. We asked whether other neuropeptides contribute to such auxiliary mechanisms. We used the gal4/UAS system to create mosaics for the neuropeptide amidating enzyme PHM; amidation is a highly specific and widespread modification of secretory peptides in Drosophila. Three different gal4 drivers restricted PHM expression to different numbers of peptidergic neurons. These mosaics displayed aberrant locomotor rhythms to degrees that paralleled the apparent complexity of the spatial patterns. Certain PHM mosaics were less rhythmic than pdf mutants and as severe as per mutants. Additional gal4 elements were added to the weakly rhythmic PHM mosaics. Although adding pdf-gal4 provided only partial improvement, adding the widely expressed tim-gal4 largely restored rhythmicity. These results indicate that, in Drosophila, peptide amidation is required for neuropeptide regulation of behavior. They also support the hypothesis that multiple amidated neuropeptides, acting upstream, downstream, or in parallel to PDF, help organize daily locomotor rhythms. PMID:11517257

  8. Effects of loratadine and cetirizine on serum levels of neuropeptides in patients with chronic urticaria.

    PubMed

    Başak, Pinar Y; Vural, Huseyin; Kazanoglu, Oya O; Erturan, Ijlal; Buyukbayram, Halil I

    2014-12-01

    H1-receptor inhibiting drugs, namely loratadine and cetirizine, were frequently used in treatment of chronic urticaria. Urticarial weal and flare reactions, a neurogenic reflex due to neuropeptides, were reported to be more effectively inhibited by cetirizine than loratadine. The aim of this study was to determine and compare the effects of systemic loratadine and cetirizine treatments on serum levels of selected neuropeptides in chronic urticaria. Treatment groups of either systemic loratadine or cetirizine (10 mg/d), consisting of 16 and 22 patients, respectively, were included. Serum levels of stem cell factor (SCF), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), and substance P (SP) were detected before and after one week of treatment with antihistamines. Serum NPY and VIP levels were significantly decreased when compared before and after treatment with antihistamines (P < 0.001 and P < 0.01, respectively). SCF and NGF values were also decreased after antihistamine treatment (P < 0.05). Post-treatment levels of CGRP were significantly higher compared with pretreatment values, while no significant difference was detected between pre and post treatment levels of SP. Cetirizine was significantly more effective than loratadine on lowering serum levels of SCF among the other neuropeptides. Systemic loratadine and cetirizine treatments in patients with chronic urticaria precisely caused variations in serum levels of neuropeptides. The predominant effect of cetirizine compared to loratadine on reducing serum SCF levels might be explained with anti-inflammatory properties of cetirizine. PMID:25209952

  9. Neuropeptide Y antagonism reduces reflex cutaneous vasoconstriction in humans.

    PubMed

    Stephens, Dan P; Saad, Adham R; Bennett, Lee Ann T; Kosiba, Wojciech A; Johnson, John M

    2004-09-01

    Previous studies have provided evidence of a non-noradrenergic contributor to reflex cutaneous vasoconstriction in humans but did not identify the transmitter responsible. To test whether neuropeptide Y (NPY) has a role, in two series of experiments we slowly reduced whole body skin temperature (TSK) from 34.5 to 31.7 degrees C. In protocol 1, Ringer solution and the NPY receptor antagonist BIBP-3226 alone were delivered intradermally via microdialysis. In protocol 2, yohimbine plus propranolol (Yoh + Pro), Yoh + Pro in combination with BIBP-3226, and Ringer solution were delivered to antagonize locally the vasomotor effects of NPY and norepinephrine. Blood flow was measured by laser Doppler flowmetry (LDF). Mean arterial blood pressure (MAP) was monitored at the finger (Finapres). In protocol 1, cutaneous vascular conductance (CVC) fell by 45%, to 55.1 +/- 5.6% of baseline at control sites (P < 0.05). At BIBP-3226-treated sites, CVC fell by 34.1% to 65.9 +/- 5.0% (P < 0.05; P < 0.05 between sites). In protocol 2, during body cooling, CVC at control sites fell by 32.6%, to 67.4 +/- 4.3% of baseline; at sites treated with Yoh + Pro, CVC fell by 18.7%, to 81.3 +/- 4.4% of baseline (P < 0.05 vs. baseline; P < 0.05 vs. control) and did not fall significantly at sites treated with BIBP-3226 + Yoh + Pro (P > 0.05; P < 0.05 vs. other sites). After cooling, exogenous norepinephrine induced vasoconstriction at control sites (P < 0.05) but not at sites treated with Yoh + Pro + BIBP-3226 (P > 0.05). These results indicate that NPY participates in sympathetically mediated cutaneous vasoconstriction in humans during whole body cooling. PMID:15165988

  10. Neuropeptide Y inhibits cholangiocarcinoma cell growth and invasion

    PubMed Central

    DeMorrow, Sharon; Onori, Paolo; Venter, Julie; Invernizzi, Pietro; Frampton, Gabriel; White, Mellanie; Franchitto, Antonio; Kopriva, Shelley; Bernuzzi, Francesca; Francis, Heather; Coufal, Monique; Glaser, Shannon; Fava, Giammarco; Meng, Fanyin; Alvaro, Domenico; Carpino, Guido; Gaudio, Eugenio

    2011-01-01

    No information exists on the role of neuropeptide Y (NPY) in cholangiocarcinoma growth. Therefore, we evaluated the expression and secretion of NPY and its subsequent effects on cholangiocarcinoma growth and invasion. Cholangiocarcinoma cell lines and nonmalignant cholangiocytes were used to assess NPY mRNA expression and protein secretion. NPY expression was assessed by immunohistochemistry in human liver biopsies. Cell proliferation and migration were evaluated in vitro by MTS assays and matrigel invasion chambers, respectively, after treatment with NPY or a neutralizing NPY antibody. The effect of NPY or NPY depletion on tumor growth was assessed in vivo after treatment with NPY or the neutralizing NPY antibody in a xenograft model of cholangiocarcinoma. NPY secretion was upregulated in cholangiocarcinoma compared with normal cholangiocytes. Administration of exogenous NPY decreased proliferation and cell invasion in all cholangiocarcinoma cell lines studied and reduced tumor cell growth in vivo. In vitro, the effects of NPY on proliferation were blocked by specific inhibitors for NPY receptor Y2, but not Y1 or Y5, and were associated with an increase in intracellular d-myo-inositol 1,4,5-trisphosphate and PKCα activation. Blocking of NPY activity using a neutralizing antibody promoted cholangiocarcinoma growth in vitro and in vivo and increased the invasiveness of cholangiocarcinoma in vitro. Increased NPY immunoreactivity in human tumor tissue occurred predominantly in the center of the tumor, with less expression toward the invasion front of the tumor. We demonstrated that NPY expression is upregulated in cholangiocarcinoma, which exerts local control on tumor cell proliferation and invasion. Modulation of NPY secretion may be important for the management of cholangiocarcinoma. PMID:21270292

  11. Effects of a Skin Neuropeptide (Substance P) on Cutaneous Microflora

    PubMed Central

    Mijouin, Lily; Hillion, Mélanie; Ramdani, Yasmina; Jaouen, Thomas; Duclairoir-Poc, Cécile; Follet-Gueye, Marie-Laure; Lati, Elian; Yvergnaux, Florent; Driouich, Azzedine; Lefeuvre, Luc; Farmer, Christine; Misery, Laurent; Feuilloley, Marc G. J.

    2013-01-01

    Background Skin is the largest human neuroendocrine organ and hosts the second most numerous microbial population but the interaction of skin neuropeptides with the microflora has never been investigated. We studied the effect of Substance P (SP), a peptide released by nerve endings in the skin on bacterial virulence. Methodology/Principal Findings Bacillus cereus, a member of the skin transient microflora, was used as a model. Exposure to SP strongly stimulated the cytotoxicity of B. cereus (+553±3% with SP 10−6 M) and this effect was rapid (<5 min). Infection of keratinocytes with SP treated B. cereus led to a rise in caspase1 and morphological alterations of the actin cytoskeleton. Secretome analysis revealed that SP stimulated the release of collagenase and superoxide dismutase. Moreover, we also noted a shift in the surface polarity of the bacteria linked to a peel-off of the S-layer and the release of S-layer proteins. Meanwhile, the biofilm formation activity of B. cereus was increased. The Thermo unstable ribosomal Elongation factor (Ef-Tu) was identified as the SP binding site in B. cereus. Other Gram positive skin bacteria, namely Staphylococcus aureus and Staphylococcus epidermidis also reacted to SP by an increase of virulence. Thermal water from Uriage-les-Bains and an artificial polysaccharide (Teflose®) were capable to antagonize the effect of SP on bacterial virulence. Conclusions/Significance SP is released in sweat during stress and is known to be involved in the pathogenesis of numerous skin diseases through neurogenic inflammation. Our study suggests that a direct effect of SP on the skin microbiote should be another mechanism. PMID:24250813

  12. Aging and long-term caloric restriction regulate neuropeptide Y receptor subtype densities in the rat brain.

    PubMed

    Veyrat-Durebex, Christelle; Quirion, Rémi; Ferland, Guylaine; Dumont, Yvan; Gaudreau, Pierrette

    2013-06-01

    The effects of aging and long-term caloric restriction (LTCR), on the regulation of neuropeptide Y (NPY) Y1, Y2 and Y5 receptors subtypes, was studied in 20-month-old male rats fed ad libitum (AL) or submitted to a 40% caloric restriction for 12 months. [(125)I]GR231118, a Y1 antagonist was used as Y1 receptor radioligand. [(125)I][Leu(31), Pro(34)]PYY, a high affinity agonist of Y1 and Y5 subtypes was used in the absence or presence of 100 nM BIBO3304 (a highly selective Y1 receptor antagonist) to assess the apparent levels of [(125)I][Leu(31), Pro(34)]PYY/BIBO3304 insensitive sites (Y5-like) from [(125)I][Leu(31), Pro(34)]PYY/BIBO3304 sensitive sites (Y1). [(125)I]PYY(3-36) was used to label the Y2 receptor. In the brain of 3-month-old AL rats, the distribution and densities of Y1, Y2 and Y5 receptors were in agreement with previous reports. In the brain of 20AL rats, a decrease of NPY receptor subtype densities in regions having important physiological functions such as the cingulate cortex, hippocampus and dentate gyrus, thalamus and hypothalamus was observed. In contrast, LTCR had multiple effects. It induced specific decreases of Y1-receptor densities in the dentate gyrus, thalamic and hypothalamic nuclei and lateral hypothalamic area and Y2-receptor densities in the suprachiasmatic nucleus of hypothalamus. Moreover, it prevented the age-induced increase in Y1-receptor densities in the ventromedial hypothalamic nucleus and decrease in the mediodorsal thalamic nucleus, and increased Y2-receptor densities in the CA2 subfield of the hippocampus. These results indicate that LTCR not only counteracts some of the deleterious effects of aging on NPY receptor subtype densities but exerts specific effects of its own. The overall impact of the regulation of NPY receptor subtypes in the brain of old calorie-restricted rats may protect the neural circuits involved in pain, emotions, feeding and memory functions. PMID:23410741

  13. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger.

    PubMed

    Krashes, Michael J; Shah, Bhavik P; Madara, Joseph C; Olson, David P; Strochlic, David E; Garfield, Alastair S; Vong, Linh; Pei, Hongjuan; Watabe-Uchida, Mitsuko; Uchida, Naoshige; Liberles, Stephen D; Lowell, Bradford B

    2014-03-13

    Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake. Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding. Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques in mice, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP, also known as ADCYAP1). Chemogenetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric-deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated. PMID:24487620

  14. Sensitivity of cross sections for elastic nucleus-nucleus scattering to halo nucleus density distributions

    SciTech Connect

    Alkhazov, G. D.; Sarantsev, V. V.

    2012-12-15

    In order to clear up the sensitivity of the nucleus-nucleus scattering to the nuclear matter distributions in exotic halo nuclei, we have calculated differential cross sections for elastic scattering of the {sup 6}He and {sup 11}Li nuclei on several nuclear targets at the energy of 0.8 GeV/nucleon with different assumed nuclear density distributions in {sup 6}He and {sup 11}Li.

  15. Intrinsic properties and neuropharmacology of midline paraventricular thalamic nucleus neurons

    PubMed Central

    Kolaj, Miloslav; Zhang, Li; Hermes, Michael L. H. J.

    2014-01-01

    Neurons in the midline and intralaminar thalamic nuclei are components of an interconnected brainstem, limbic and prefrontal cortex neural network that is engaged during arousal, vigilance, motivated and addictive behaviors, and stress. To better understand the cellular mechanisms underlying these functions, here we review some of the recently characterized electrophysiological and neuropharmacological properties of neurons in the paraventricular thalamic nucleus (PVT), derived from whole cell patch clamp recordings in acute rat brain slice preparations. PVT neurons display firing patterns and ionic conductances (IT and IH) that exhibit significant diurnal change. Their resting membrane potential (RMP) is maintained by various ionic conductances that include inward rectifier (Kir), hyperpolarization-activated nonselective cation (HCN) and TWIK-related acid sensitive (TASK) K+ channels. Firing patterns are regulated by high voltage-activated (HVA) and low voltage-activated (LVA) Ca2+ conductances. Moreover, transient receptor potential (TRP)-like nonselective cation channels together with Ca2+- and Na+-activated K+ conductances (KCa; KNa) contribute to unique slow afterhyperpolarizing potentials (sAHPs) that are generally not detectable in lateral thalamic or reticular thalamic nucleus neurons. The excitability of PVT neurons is also modulated by activation of neurotransmitter receptors associated with afferent pathways to PVT and other thalamic midline nuclei. We report on receptor-mediated actions of GABA, glutamate, monoamines and several neuropeptides: arginine vasopressin, gastrin-releasing peptide, thyrotropin releasing hormone and the orexins (hypocretins). This review represents an initial survey of intrinsic and transmitter-sensitive ionic conductances that are deemed to be unique to this population of midline thalamic neurons, information that is fundamental to an appreciation of the role these thalamic neurons may play in normal central nervous system

  16. Spontaneous development of arcuate single-sided subduction in global 3-D mantle convection models with a free surface

    NASA Astrophysics Data System (ADS)

    Crameri, Fabio; Tackley, Paul

    2014-05-01

    The work presented aims at a better understanding of plate tectonics, a crucial dynamical feature within the global framework of mantle convection. Special focus is given to the interaction of subduction-related mantle flow and surface topography. Thereby, the application of a numerical model with two key functional requirements is essential: an evolution over a long time period to naturally model mantle flow and a physically correct topography calculation. The global mantle convection model presented in Crameri et al. (2012a) satisfies both of these requirements. First, it is efficiently calculated by the finite-volume code Stag-YY (e.g., Tackley 2008) using a multi-grid method on a fully staggered grid. Second, it applies the sticky-air method (Matsumoto and Tomoda 1983; Schmeling et al, 2008) and thus approximates a free surface when the sticky-air parameters are chosen carefully (Crameri et al., 2012b). This leads to dynamically self-consistent mantle convection with realistic, single-sided subduction. New insights are thus gained into the interplay of obliquely sinking plates, toroidal mantle flow and the arcuate shape of slabs and trenches. Numerous two-dimensional experiments provide optimal parameter setups that are applied to three-dimensional models in Cartesian and fully spherical geometries. Features observed and characterised in the latter experiments give important insight into the strongly variable behaviour of subduction zones along their strike. This includes (i) the spontaneous development of arcuate trench geometry, (ii) regional subduction polarity reversals and slab tearing, and the newly discovered features (iii) 'slab tunnelling' and (iv) 'back-slab spiral flow'. Overall, this study demonstrates the strong interaction between surface topography and mantle currents and highlights the variability of subduction zones and their individual segments. REFERENCES Crameri, F., P. J. Tackley, I. Meilick, T. V. Gerya, and B. J. P. Kaus (2012a), A free

  17. Complete Arcuate Foramen Precluding C1 Lateral Mass Screw Fixation in a Patient with Rheumatoid Arthritis: Case Report

    PubMed Central

    Huang, Michael J; Glaser, John A

    2003-01-01

    Case report of a complete arcuate foramen in a human atlas vertebra inhibiting the placement of lateral mass screw instrumentation at C1. Our objective is to report the presentation of the case, the operative considerations, and the management for this anatomic variation. The groove for the vertebral artery on the posterolateral surface of the atlas (C1) varies in size and depth from a slight impression to a clear sulcus. With anomalous ossification the sulcus can be bridged which results in a posterolateral tunnel within the posterior arch of the atlas. With increasing rates of screw fixation instrumentation that include the atlas, it is of paramount importance to know the location and course of the vertebral artery in relation to the planned route of instrumentation. The patient underwent a posterolateral fusion from C1 to C4 using autogenous iliac crest bone graft. Internal fixation from C2 to C4 was obtained using lateral mass screw instrumentation. After the vertebral artery was identified passing through the posterior arch of C1, sublaminar wires were utilized for fixation from C1 to C2. The patient responded well to surgical intervention without complications. Abnormal vertebral artery coursing through a posterolateral tunnel in the posterior arch of C1 has been described and its incidence has a range from 1.14% to 18%. When this variant is present, lateral mass screw fixation at C1 may be contraindicated. We recommend close scrutiny of preoperative radiographs to avoid the possibility of endangering the vertebral artery when this situation exists. PMID:14575258

  18. Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie lateralized language function in the human brain

    PubMed Central

    Takaya, Shigetoshi; Kuperberg, Gina R.; Liu, Hesheng; Greve, Douglas N.; Makris, Nikos; Stufflebeam, Steven M.

    2015-01-01

    The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting-state functional MRI (fMRI) and task-related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that the left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyrus to the mid part of the superior temporal sulcus and the middle temporal gyrus, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyrus. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. The unique feature of the left AF is discussed in the context of the human capacity for language. PMID:26441551

  19. Adeno-Associated Viral Vector-Induced Overexpression of Neuropeptide Y Y2 Receptors in the Hippocampus Suppresses Seizures

    ERIC Educational Resources Information Center

    Woldbye, David P. D.; Angehagen, Mikael; Gotzsche, Casper R.; Elbrond-Bek, Heidi; Sorensen, Andreas T.; Christiansen, Soren H.; Olesen, Mikkel V.; Nikitidou, Litsa; Hansen, Thomas v. O.; Kanter-Schlifke, Irene; Kokaia, Merab

    2010-01-01

    Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure suppression by neuropeptide Y in the hippocampus is…

  20. Agonists/Antagonists of the insect kinin and pyrokinin/PBAN neuropeptide classes as tools for rational pest control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The IK and PK/PBAN insect neuropeptide classes regulate critical aspects of water balance, digestion, reproduction, defense and development in insects. These neuropeptides are nonetheless subject to degradation by peptidases in the hemolymph and gut of insects and, for the most part, lack efficient ...

  1. Identification of Neuropeptide Receptors Expressed by Melanin-Concentrating Hormone Neurons

    PubMed Central

    Parks, Gregory S.; Wang, Lien; Wang, Zhiwei; Civelli, Olivier

    2014-01-01

    Melanin-concentrating Hormone (MCH) is a 19 amino acid cyclic neuropeptide that acts in rodents via the MCH receptor 1 (MCHR1) to regulate a wide variety of physiological functions. MCH is produced by a distinct population of neurons located in the lateral hypothalamus (LH) and zona incerta (ZI) but MCHR1 mRNA is widely expressed throughout the brain. The physiological responses and behaviors regulated by the MCH system have been investigated, but less is known about how MCH neurons are regulated. The effects of most classical neurotransmitters on MCH neurons have been studied, but those of neuropeptides are poorly understood. In order to gain insight into how neuropeptides regulate the MCH system, we investigated which neuropeptide receptors are expressed by MCH neurons using double in situ hybridization. In all, twenty receptors, selected based upon either a suspected interaction with the MCH system or demonstrated high expression levels in the LH and ZI, were tested to determine whether they are expressed by MCH neurons. Overall, eleven neuropeptide receptors were found to exhibit significant colocalization with MCH neurons: Nociceptin / Orphanin FQ Opioid receptor (NOP), MCHR1, both Orexin receptors (ORX), Somatostatin receptor 1 and 2 (SSTR1, SSTR2), the Kisspeptin receotor (KissR1), Neurotensin receptor 1 (NTSR1), Neuropeptide S receptor (NPSR), Cholecystokinin receptor A (CCKAR) and the κ-opioid receptor (KOR). Of these receptors, six have never before been linked to the MCH system. Surprisingly, several receptors thought to regulate MCH neurons displayed minimal colocalization with MCH, suggesting that they may not directly regulate the MCH system. PMID:24978951

  2. Expression Profiles of Neuropeptides, Neurotransmitters, and Their Receptors in Human Keratocytes In Vitro and In Situ

    PubMed Central

    Słoniecka, Marta; Le Roux, Sandrine; Boman, Peter; Byström, Berit; Zhou, Qingjun; Danielson, Patrik

    2015-01-01

    Keratocytes, the quiescent cells of the corneal stroma, play a crucial role in corneal wound healing. Neuropeptides and neurotransmitters are usually associated with neuronal signaling, but have recently been shown to be produced also by non-neuronal cells and to be involved in many cellular processes. The aim of this study was to assess the endogenous intracellular and secreted levels of the neuropeptides substance P (SP) and neurokinin A (NKA), and of the neurotransmitters acetylcholine (ACh), catecholamines (adrenaline, noradrenaline and dopamine), and glutamate, as well as the expression profiles of their receptors, in human primary keratocytes in vitro and in keratocytes of human corneal tissue sections in situ. Cultured keratocytes expressed genes encoding for SP and NKA, and for catecholamine and glutamate synthesizing enzymes, as well as genes for neuropeptide, adrenergic and ACh (muscarinic) receptors. Keratocytes in culture produced SP, NKA, catecholamines, ACh, and glutamate, and expressed neurokinin-1 and -2 receptors (NK-1R and NK-2R), dopamine receptor D2, muscarinic ACh receptors, and NDMAR1 glutamate receptor. Human corneal sections expressed SP, NKA, NK-1R, NK-2R, receptor D2, choline acetyl transferase (ChAT), M3, M4 and M5 muscarinic ACh receptors, glutamate, and NMDAR1, but not catecholamine synthesizing enzyme or the α1 and β2 adrenoreceptors, nor M1 receptor. In addition, expression profiles assumed significant differences between keratocytes from the peripheral cornea as compared to those from the central cornea, as well as differences between keratocytes cultured under various serum concentrations. In conclusion, human keratocytes express an array of neuropeptides and neurotransmitters. The cells furthermore express receptors for neuropeptides/neurotransmitters, which suggests that they are susceptible to stimulation by these substances in the cornea, whether of neuronal or non-neuronal origin. As it has been shown that neuropeptides

  3. Double Nucleus in M83

    NASA Astrophysics Data System (ADS)

    Mast, Damián; Díaz, Rubén J.; Agüero, M. Paz

    2006-03-01

    M83 is one of the nearest galaxies with enhanced nuclear star formation, and it presents one of the best opportunities to study the kinematics and physical properties of a circumnuclear starburst. Our three-dimensional spectroscopy data in the R band confirm the presence of a secondary nucleus or mass concentration (previously suggested by Thatte and coworkers). We determine the position of this hidden nucleus, which would be more massive than the visible one and was not detected in the optical Hubble Space Telescope images due, probably, to the strong dust extinction. Using a Keplerian approximation, we estimated for the optical nucleus a mass of (5.0+/-0.8)×106 Msolar/sini (r<1.5"), and for the hidden nucleus, located 4''+/-1'' to the northwest (position angle of 271deg+/-15deg) of the optical nucleus, a mass of (1.00+/-0.08)×107 Msolar/sini (r<1.5"). The emission-line ratio map also unveils the presence of a second circumnuclear ring structure, previously discovered by IR imaging (Elmegreen and coworkers). The data allow us to resolve the behavior of the interstellar medium inside the circumnuclear ring and around the binary mass concentration.

  4. Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in multiple sclerosis

    SciTech Connect

    Vecsei, L.; Csala, B.; Widerloev, E.E.; Ekman, R.; Czopf, J.; Palffy, G. )

    1990-09-01

    The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.

  5. THE NEUROPEPTIDE VIP: DIRECT EFFECTS ON IMMUNE CELLS AND INVOLVEMENT IN INFLAMMATORY AND AUTOIMMUNE DISEASES

    PubMed Central

    Ganea, Doina; Hooper, Kirsten M.; Kong, Weimin

    2015-01-01

    Neuropeptides represent an important category of endogenous contributors to the establishment and maintenance of immune deviation in immune privileged organs such as the CNS, and in the control of acute inflammation in the peripheral immune organs. Vasoactive intestinal peptide (VIP) is a major immunoregulatory neuropeptide widely distributed in the central and peripheral nervous system. In addition to neurons, VIP is synthesized by immune cells which also express VIP receptors. Here we review the current information on VIP production and VIP receptor mediated effects in the immune system, the role of endogenous and exogenous VIP in inflammatory and autoimmune disorders, and present and future VIP therapeutic approaches. PMID:25422088

  6. Vasopressin: Behavioral Roles of an “Original” Neuropeptide

    PubMed Central

    Caldwell, Heather K.; Lee, Heon-Jin; Macbeth, Abbe H.; Young, W. Scott

    2008-01-01

    Vasopressin (Avp) is mainly synthesized in the magnocellular cells of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) whose axons project to the posterior pituitary. Avp is then released into the blood stream upon appropriate stimulation (e.g., hemorrhage or dehydration) to act at the kidneys and blood vessels. The brain also contains several populations of smaller, parvocellular neurons whose projections remain within the brain. These populations are located within the PVN, bed nucleus of the stria terminalis (BNST), medial amygdala (MeA) and suprachiasmatic nucleus (SCN). Since the 1950's, research examining the roles of Avp in the brain and periphery has intensified. The development of specific agonists and antagonists for Avp receptors has allowed for a better elucidation of its contributions to physiology and behavior. Anatomical, pharmacological and transgenic, including “knockout,” animal studies, have implicated Avp in the regulation of various social behaviors across species. Avp plays a prominent role in the regulation of aggression, generally of facilitating or promoting it. Affiliation and certain aspects of pair-bonding are also influenced by Avp. Memory, one of the first brain functions of Avp that was investigated, has been implicated especially strongly in social recognition. The roles of Avp in stress, anxiety, and depressive states are areas of active exploration. In this review, we concentrate on the scientific progress that has been made on understanding the role of Avp in regulating of these and other behaviors across species, as well as discuss the implications for human behavior. PMID:18053631

  7. Unilateral optic nerve transection alters light response of suprachiasmatic nucleus and intergeniculate leaflet

    NASA Technical Reports Server (NTRS)

    Tang, I-Hsiung; Murakami, Dean M.; Fuller, Charles A.

    2002-01-01

    The suprachiasmatic nucleus (SCN), the circadian pacemaker, receives photic input directly from the retina to synchronize the pacemaker to the environment. Additionally, the intergeniculate leaflet (IGL), which innervates the SCN, is known to modulate the retinal photic input to the SCN. To further understand the role of the IGL in mediating the photic input to the SCN, this study examined the effects of unilateral optic nerve transection (UONx) on the photic response of the SCN and IGL in adult and neonatal hamsters. UONx led to an overall reduction in light-induced c-Fos expression in the SCN and IGL. The c-Fos expression was greater in the SCN ipsilateral to the remaining eye, despite a symmetrically bilateral retinohypothalamic tract projection as revealed by intraocular injection of horseradish peroxidase. In contrast, UONx led to a greater c-Fos expression in the contralateral IGL. The contralateral IGL of UONx animals also revealed more neuropeptide Y-immunoreactive neurons, while the ipsilateral SCN of these animals exhibited a denser neuropeptide Y terminal field. The neonates with UONx showed a similar pattern with a slight compensation of the photic-induced c-Fos in the SCN. This study suggests that the IGL may have an ipsilateral inhibitory effect in mediating retinal photic input to the SCN.

  8. Cultured human synovial fibroblasts rapidly metabolize kinins and neuropeptides.

    PubMed Central

    Bathon, J M; Proud, D; Mizutani, S; Ward, P E

    1992-01-01

    Kinins and substance P have been implicated in the pathogenesis of inflammatory arthritis by virtue of their abilities to induce vasodilation, edema, and pain. The relative biological potencies of these peptides in vivo would depend at least in part upon their rates of catabolism in the joint. We hypothesized that human synovial lining cells may regulate intraarticular levels of kinins and neuropeptides via degradation by cell surface-associated peptidases. We exposed intact human synovial fibroblasts to kinins and substance P, in the presence or absence of specific peptidase inhibitors, and measured the amount of intact substrate remaining and degradation product(s) generated over time. Aminopeptidase M (AmM; EC 3.4.11.2), neutral endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11), and dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) were identified on the cell surface of synovial cells. Bradykinin degradation was due entirely to NEP-24.11 (1.39 +/- 0.29 nmol/min per well). Lysylbradykinin was also degraded by NEP-24.11 (0.80 +/- 0.19 nmol/min per well); however, in the presence of phosphoramidon, AmM-mediated conversion to bradykinin (3.74 +/- 0.46 nmol/min per well) could be demonstrated. The combined actions of NEP-24.11 (0.93 +/- 0.15 nmol/min per well) and DAP IV (0.84 +/- 0.18 nmol/min per well) were responsible for the degradation of substance P. AmM (2.44 +/- 0.33 nmol/min per well) and NEP-24.11 (1.30 +/- 0.45 nmol/min per well) were responsible for the degradation of the opioid peptide, [Leu5]enkephalin. The identity of each of the three peptidases was confirmed via synthetic substrate hydrolysis, inhibition profile, and immunological identification. The profiles of peptidase enzymes identified in cells derived from rheumatoid and osteoarthritic joints were identical. These data demonstrate the human synovial fibroblast to be a rich source of three specific peptidases and suggest that it may play a prominent role in regulating peptide levels in the joint

  9. Nucleus management with irrigating vectis.

    PubMed

    Srinivasan, Aravind

    2009-01-01

    The main objective in modern cataract surgery is to achieve a better unaided visual acuity with rapid post-surgical recovery and minimal surgery-related complications. Early visual rehabilitation and better unaided vision can be achieved only by reducing the incision size. In manual small incision cataract surgery (MSICS), incision is between 5.5 to 7 mm. Once the nucleus is prolapsed into the anterior chamber, it can be extracted through the tunnel. Nucleus extraction with an irrigating vectis is a very simple technique, which combines mechanical and hydrostatic forces to express out the nucleus. This technique is time-tested with good results and more than 95% of nuclei in MSICS are extracted in this way offering all the merits of phacoemulsification with the added benefits of having wider applicability, better safety, shorter learning curve and lower cost. PMID:19075403

  10. Cometary nucleus and active regions

    NASA Technical Reports Server (NTRS)

    Whipple, F. L.

    1984-01-01

    On the basis of the icy conglomerate model of cometary nuclei, various observations demonstrate the spotted nature of many or most nuclei, i.e., regions of unusual activity, either high or low. Rotation periods, spin axes and even precession of the axes are determined. The observational evidence for variations in activity over the surfaces of cometary nuclei are listed and discussed. On June 11 the comet IRAS-ARAKI-ALCOCK approached the Earth to a distance of 0.031 AU, the nearest since C/Lexell, 1770 I, providing a unique opportunity for near-nucleus observations. Preliminary analysis of these images establishes the spin axis of the nucleus, with an oblioquity to the orbit plane of approximately 50 deg, and a lag angle of sublimation approximately 35 deg from the solar meridian on the nucleus. Asymmetries of the inner coma suggests a crazy-quilt distribution of ices with differing volatility over the surface of the nucleus. The observations of Comet P/Homes 1892 III, exhibiting two 8-10 magnitude bursts, are carefully analyzed. The grazing encounter produced, besides the first great burst, an active area on the nucleus, which was rotating retrograde with a period of 16.3hr and inclination nearly 180 deg. After the first burst the total magnitude fell less than two magnitudes from November 7 to November 30 (barely naked eye) while the nuclear region remained diffuse or complex, rarely if ever showing a stellar appearance. The fading was much more rapid after the second burst. The grazing encounter distributed a volume of large chunks in the neighborhood of the nucleus, maintaining activity for weeks.

  11. Formin' actin in the nucleus.

    PubMed

    Baarlink, Christian; Grosse, Robert

    2014-01-01

    Many if not most proteins can, under certain conditions, change cellular compartments, such as, for example, shuttling from the cytoplasm to the nucleus. Thus, many proteins may exert functions in various and very different subcellular locations, depending on the signaling context. A large amount of actin regulatory proteins has been detected in the mammalian cell nucleus, although their potential roles are much debated and are just beginning to emerge. Recently, members of the formin family of actin nucleators were also reported to dynamically localize to the nuclear environment. Here we discuss our findings that specific diaphanous-related formins can promote nuclear actin assembly in a signal-dependent manner. PMID:24637338

  12. Acridine: a versatile heterocyclic nucleus.

    PubMed

    Kumar, Ramesh; Kaur, Mandeep; Kumari, Meena

    2012-01-01

    Acridine is a heterocyclic nucleus. It plays an important role in various medicines. A number of therapeutic agents are based on acridine nucleus such as quinacrine (antimalarial), acriflavine and proflavine (antiseptics), ethacridine (abortifacient), amsacrine and nitracine (anticancer), and tacrine. Acridine is obtained from high boiling fraction of coal tar. It is also obtained in nature from plant and marine sources. Acridine undergoes a number of reactions such as nucleophilic addition, electrophilic substitution, oxidation, reduction, reductive alkylation and photoalkylation. The present review article summarizes the synthesis, reaction, literature review and pharmaceutical importance of acridine. PMID:22574501

  13. Cocaine- and amphetamine-regulated transcript peptide (CART) in the brain of zebra finch, Taeniopygia guttata: Organization, interaction with neuropeptide Y, and response to changes in energy status.

    PubMed

    Singh, Omprakash; Kumar, Santosh; Singh, Uday; Kumar, Vinod; Lechan, Ronald M; Singru, Praful S

    2016-10-15

    Cocaine- and amphetamine-regulated transcript (CART) has emerged as a potent anorectic agent. CART is widely distributed in the brain of mammals, amphibians, and teleosts, but the relevant information in avian brain is not available. In birds, CART inhibits food intake, whereas neuropeptide Y (NPY), a well-known orexigenic peptide, stimulates it. How these neuropeptides interact in the brain to regulate energy balance is not known. We studied the distribution of CART-immunoreactivity in the brain of zebra finch, Taeniopygia guttata, its interaction with NPY, and their response to dynamic energy states. CART-immunoreactive fibers were found in the subpallium, hypothalamus, midbrain, and brainstem. Conspicuous CART-immunoreactive cells were observed in the bed nucleus of the stria terminalis, hypothalamic paraventricular, supraoptic, dorsomedial, infundibular (IN), lateral hypothalamic, Edinger-Westphal, and parabrachial nuclei. Hypothalamic sections of fed, fasted, and refed animals were immunostained with cFos, NPY, and CART antisera. Fasting dramatically increased cFos- and NPY-immunoreactivity in the IN, followed by rapid reduction by 2 hours and restoration to normal fed levels 6-10 hours after refeeding. CART-immunoreactive fibers in IN showed a significant reduction during fasting and upregulation with refeeding. Within the IN, double immunofluorescence revealed that 94 ± 2.1% of NPY-immunoreactive neurons were contacted by CART-immunoreactive fibers and 96 ± 2.8% NPY-immunoreactive neurons expressed cFos during fasting. Compared to controls, superfused hypothalamic slices of fasted birds treated with CART-peptide showed a significant reduction (P < 0.001) in NPY-immunoreactivity in the IN. As in other vertebrates, CART in the brain of T. guttata may perform several functions, and has a particularly important role in the hypothalamic regulation of energy homeostasis. J. Comp. Neurol. 524:3014-3041, 2016. © 2016 Wiley Periodicals, Inc. PMID:27018984

  14. Functionalized active-nucleus complex sensor

    DOEpatents

    Pines, Alexander; Wemmer, David E.; Spence, Megan; Rubin, Seth

    2003-11-25

    A functionalized active-nucleus complex sensor that selectively associates with one or more target species, and a method for assaying and screening for one or a plurality of target species utilizing one or a plurality of functionalized active-nucleus complexes with at least two of the functionalized active-nucleus complexes having an attraction affinity to different corresponding target species. The functionalized active-nucleus complex has an active-nucleus and a targeting carrier. The method involves functionalizing an active-nucleus, for each functionalized active-nucleus complex, by incorporating the active-nucleus into a macromolucular or molecular complex that is capable of binding one of the target species and then bringing the macromolecular or molecular complexes into contact with the target species and detecting the occurrence of or change in a nuclear magnetic resonance signal from each of the active-nuclei in each of the functionalized active-nucleus complexes.

  15. Petrology, geochronology and emplacement model of the giant 1.37 Ga arcuate Lake Victoria Dyke Swarm on the margin of a large igneous province in eastern Africa

    NASA Astrophysics Data System (ADS)

    Mäkitie, Hannu; Data, Gabriel; Isabirye, Edward; Mänttäri, Irmeli; Huhma, Hannu; Klausen, Martin B.; Pakkanen, Lassi; Virransalo, Petri

    2014-09-01

    A comprehensive description of the petrography, geochemical composition, Sm-Nd data and intrinsic field relationships of a giant arcuate Mesoproterozoic mafic dyke swarm in SW Uganda is presented for the first time. The swarm is ∼100 km wide and mainly hosted in the Palaeoproterozoic Rwenzori Belt between the Mesoproterozoic Karagwe-Ankole Belt and the Archaean Uganda Block. The dykes trend NW-SE across Uganda, but can be correlated across Lake Victoria to another set of arcuate aeromagnetic anomalies that continue southwards into Tanzania, resulting in a remarkably large semi-circular swarm with an outer diameter of ∼500 km. We propose that this unique giant dyke structure be named the Lake Victoria Dyke Swarm (LVDS). The dykes are tholeiites with Mg numbers between 0.69 and 0.44, and with inherited marked negative Nb and P anomalies in spider diagrams. Two dykes provide Sm-Nd mineral ages of 1368 ± 41 Ma and 1374 ± 42 Ma, with initial εNd values of -2.3 and -3.2, and 87Sr/86Sr ratios of ∼0.706-0.709. Geotectonic discrimination diagrams for the swarm exhibit more arc type than within-plate tectonic signatures, but this is in accordance with systematic enrichments in LREE, U and Th in the dolerites, more likely due to the involvement of the continental lithosphere during their petrogenesis. The LVDS is coeval with a regional ∼1375 Ma bimodal magmatic event across nearby Burundi, Rwanda and NW Tanzania, which can collectively be viewed as a large igneous province (LIP). It also indicates that the nearby Karagwe-Ankole Belt sequences - bracketed between 1.78 and 1.37 Ga and assumed by some to have been deposited within intracratonic basins - were capped by flood basalts that have subsequently been removed by erosion. Different geochemical signatures (e.g. LaN/SmN) suggest that most of the arcuate swarm was derived from an enriched SCLM, whereas related intrusions in the centre of this semi-circular segment have more or less enriched asthenospheric mantle

  16. Stress increases GABAergic neurotransmission in CRF neurons of the central amygdala and bed nucleus stria terminalis.

    PubMed

    Partridge, John G; Forcelli, Patrick A; Luo, Ruixi; Cashdan, Jonah M; Schulkin, Jay; Valentino, Rita J; Vicini, Stefano

    2016-08-01

    Corticotrophin Releasing Factor (CRF) is a critical stress-related neuropeptide in major output pathways of the amygdala, including the central nucleus (CeA), and in a key projection target of the CeA, the bed nucleus of the stria terminalis (BnST). While progress has been made in understanding the contributions and characteristics of CRF as a neuropeptide in rodent behavior, little attention has been committed to determine the properties and synaptic physiology of specific populations of CRF-expressing (CRF(+)) and non-expressing (CRF(-)) neurons in the CeA and BnST. Here, we fill this gap by electrophysiologically characterizing distinct neuronal subtypes in CeA and BnST. Crossing tdTomato or channelrhodopsin-2 (ChR2-YFP) reporter mice to those expressing Cre-recombinase under the CRF promoter allowed us to identify and manipulate CRF(+) and CRF(-) neurons in CeA and BnST, the two largest areas with fluorescently labeled neurons in these mice. We optogenetically activated CRF(+) neurons to elicit action potentials or synaptic responses in CRF(+) and CRF(-) neurons. We found that GABA is the predominant co-transmitter in CRF(+) neurons within the CeA and BnST. CRF(+) neurons are highly interconnected with CRF(-) neurons and to a lesser extent with CRF(+) neurons. CRF(+) and CRF(-) neurons differentially express tonic GABA currents. Chronic, unpredictable stress increase the amplitude of evoked IPSCs and connectivity between CRF(+) neurons, but not between CRF(+) and CRF(-) neurons in both regions. We propose that reciprocal inhibition of interconnected neurons controls CRF(+) output in these nuclei. PMID:27016019

  17. Neuropeptide-like precursor 4 is uniquely expressed during pupal diapause in the flesh fly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Suppression subtractive hybridization comparing brains from diapausing and nondiapausing pupae of the flesh fly, Sarcophaga crassipalpis, suggested that the gene encoding neuropeptide-like precursor 4 (Nplp4) was uniquely expressed during diapause. We have sequenced the full-length cDNA encoding Npl...

  18. Prevertebrate Local Gene Duplication Facilitated Expansion of the Neuropeptide GPCR Superfamily.

    PubMed

    Yun, Seongsik; Furlong, Michael; Sim, Mikang; Cho, Minah; Park, Sumi; Cho, Eun Bee; Reyes-Alcaraz, Arfaxad; Hwang, Jong-Ik; Kim, Jaebum; Seong, Jae Young

    2015-11-01

    In humans, numerous genes encode neuropeptides that comprise a superfamily of more than 70 genes in approximately 30 families and act mainly through rhodopsin-like G protein-coupled receptors (GPCRs). Two rounds of whole-genome duplication (2R WGD) during early vertebrate evolution greatly contributed to proliferation within gene families; however, the mechanisms underlying the initial emergence and diversification of these gene families before 2R WGD are largely unknown. In this study, we analyzed 25 vertebrate rhodopsin-like neuropeptide GPCR families and their cognate peptides using phylogeny, synteny, and localization of these genes on reconstructed vertebrate ancestral chromosomes (VACs). Based on phylogeny, these GPCR families can be divided into five distinct clades, and members of each clade tend to be located on the same VACs. Similarly, their neuropeptide gene families also tend to reside on distinct VACs. Comparison of these GPCR genes with those of invertebrates including Drosophila melanogaster, Caenorhabditis elegans, Branchiostoma floridae, and Ciona intestinalis indicates that these GPCR families emerged through tandem local duplication during metazoan evolution prior to 2R WGD. Our study describes a presumptive evolutionary mechanism and development pathway of the vertebrate rhodopsin-like GPCR and cognate neuropeptide families from the urbilaterian ancestor to modern vertebrates. PMID:26337547

  19. Feed intake of gilts following intracerebroventicular injection of the novel hypothalamic RFamide (RFa) neuropeptide, 26RFa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    RFamide (RFa) peptides have been implicated in a broad spectrum of biological processes including energy expenditure and feed intake. 26RFa is a recently discovered hypothalamic neuropeptide that altered the release of pituitary hormones and stimulated feed intake via a NPY-specific mechanism in rat...

  20. Transgenic n-3 PUFAs enrichment leads to weight loss via modulating neuropeptides in hypothalamus.

    PubMed

    Ma, Shuangshuang; Ge, Yinlin; Gai, Xiaoying; Xue, Meilan; Li, Ning; Kang, Jingxuan; Wan, Jianbo; Zhang, Jinyu

    2016-01-12

    Body weight is related to fat mass, which is associated with obesity. Our study explored the effect of fat-1 gene on body weight in fat-1 transgenic mice. In present study, we observed that the weight/length ratio of fat-1 transgenic mice was lower than that of wild-type mice. The serum levels of triglycerides (TG), cholesterol (CT), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and blood glucose (BG) in fat-1 transgenic mice were all decreased. The weights of peri-bowels fat, perirenal fat and peri-testicular fat in fat-1 transgenic mice were reduced. We hypothesized that increase of n-3 PUFAs might alter the expression of hypothalamic neuropeptide genes and lead to loss of body weight in fat-1 transgenic mice. Therefore, we measured mRNA levels of appetite neuropeptides, Neuropeptide Y (NPY), Agouti-related peptides (AgRP), Proopiomelanocortin (POMC), Cocaine and amphetamine regulated transcript (CART), ghrelin and nesfatin-1 in hypothalamus by real-time PCR. Compared with wild-type mice, the mRNA levels of CART, POMC and ghrelin were higher, while the mRNA levels of NPY, AgRP and nesfatin-1 were lower in fat-1 transgenic mice. The results indicate that fat-1 gene or n-3 PUFAs participates in regulation of body weight, and the mechanism of this phenomenon involves the expression of appetite neuropeptides and lipoproteins in fat-1 transgenic mice. PMID:26610903

  1. Towards the development of novel pest management agents based upon insect kinin neuropeptide analogs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insect kinin neuropeptides share a common C-terminal pentapeptide sequence Phe1-Xaa123-Xaa23-Trp4-Gly5-NH2 (Xaa12=His, Asn, Phe, Ser or Try; Xaa23=Pro, Ser, or Ala) and have been isolated from a number of insects. They have been associated with the regulation of such diverse processes as hindgut co...

  2. Mode of action of an insect neuropeptide Leucopyrokinin (LPK) on pupariation in fleshfly (Sarcophaga bullata) larvae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An insect neuropeptide leucopyrokinin (LPK) (pQTSFTPRLamide) accelerates pupariation in wandering larvae of the fleshfly Sarcophaga bullata. The period of sensitivity to the action of LPK begins approximately 4 h before pupariation. Within this period the degree of acceleration of contraction into t...

  3. Peripheral site of action of levodropropizine in experimentally-induced cough: role of sensory neuropeptides.

    PubMed

    Lavezzo, A; Melillo, G; Clavenna, G; Omini, C

    1992-06-01

    The mechanism of action of levodropropizine has been investigated in different models of experimentally-induced cough in guinea-pigs. In particular it has been demonstrated that the antitussive drug has a peripheral site of action by injecting the drug intracerebroventricularly (i.c.v.). In these experiments levodropropizine (40 micrograms/50 microliters i.c.v.) did not prevent electrically-induced cough. On the other hand, codeine (5 micrograms/50 microliters i.c.v.) markedly prevented coughing. A difference in the potency ratio of levodropropizine and codeine has been demonstrated in capsaicin-induced cough; after oral administration, codeine was about two to three times more potent than levodropropizine. However, after aerosol administration the two compounds were equipotent. These data might suggest a peripheral site of action for levodropropizine which is related to sensory neuropeptides. Further support for the role of sensory neuropeptides in the mechanism of action of levodropropizine comes from the results obtained in capsaicin-desensitized animals. In this experimental model levodropropizine failed to prevent the vagally elicited cough in neuropeptide-depleted animals, whereas codeine did not differentiate between control and capsaicin-treated animals. In conclusion, our results support the suggestion that levodropropizine has a peripheral site of action. In addition, the interference with the sensory neuropeptide system may explain, at least in part, its activity in experimentally-induced cough. PMID:1611233

  4. Genomic and peptidomic analyses of the neuropeptides from the emerging pest, Drosophila suzukii.

    PubMed

    Audsley, Neil; Down, Rachel E; Isaac, R Elwyn

    2015-06-01

    Drosophila suzukii is a highly polyphagous invasive pest which has been recently introduced into Europe and North America, where it is causing severe economic losses through larval infestations of stone and berry fruits. The peptidome of the selected nervous tissues of adult D. suzukii was investigated as a first step in identifying potential targets for the development of novel insecticides. Through in silico analyses of the D. suzukii genome databases 28 neuropeptide families, comprising more than 70 predicted peptides were identified. Using a combination of liquid chromatography and mass spectrometry of tissue extracts, 33 predicted peptides, representing 15 different peptide families were identified by their molecular masses and a total of 17 peptide sequences were confirmed by ion fragmentation. A comparison between the peptides and precursors of D. suzukii and D. melanogaster shows they are highly conserved, with differences only identified in the amino acid sequences of the peptides encoded in the FMRFamide, hugin and ecydysis triggering hormone precursors. All other peptides predicted and identified from D. suzukii appear to be identical to those previously characterized from D. melanogaster. Adipokinetic hormone was only identified in the corpus cardiacum, other peptides present included short neuropeptide F, a pyrokinin and myosuppressin, the latter of which was the only peptide identified from the crop nerve bundle. Peptides present in extracts of the brain and/or thoracico-abdominal ganglion included allatostatins, cardioacceleratory peptide 2b, corazonin, extended FMRFamides, pyrokinins, myoinihibitory peptides, neuropeptide-like precursor 1, SIFamide, short neuropeptide F, kinin, sulfakinins and tachykinin related peptides. PMID:25158078

  5. Microglia-Induced Maladaptive Plasticity Can Be Modulated by Neuropeptides In Vivo

    PubMed Central

    Morara, Stefano; Colangelo, Anna Maria; Provini, Luciano

    2015-01-01

    Microglia-induced maladaptive plasticity is being recognized as a major cause of deleterious self-sustaining pathological processes that occur in neurodegenerative and neuroinflammatory diseases. Microglia, the primary homeostatic guardian of the central nervous system, exert critical functions both during development, in neural circuit reshaping, and during adult life, in the brain physiological and pathological surveillance. This delicate critical role can be disrupted by neural, but also peripheral, noxious stimuli that can prime microglia to become overreactive to a second noxious stimulus or worsen underlying pathological processes. Among regulators of microglia, neuropeptides can play a major role. Their receptors are widely expressed in microglial cells and neuropeptide challenge can potently influence microglial activity in vitro. More relevantly, this regulator activity has been assessed also in vivo, in experimental models of brain diseases. Neuropeptide action in the central nervous system has been associated with beneficial effects in neurodegenerative and neuroinflammatory pathological experimental models. This review describes some of the mechanisms of the microglia maladaptive plasticity in vivo and how neuropeptide activity can represent a useful therapeutical target in a variety of human brain pathologies. PMID:26273481

  6. Higgs and Particle Production in Nucleus-Nucleus Collisions

    NASA Astrophysics Data System (ADS)

    Liu, Zhe

    We apply a diagrammatic approach to study Higgs boson, a color-neutral heavy particle, pro- duction in nucleus-nucleus collisions in the saturation framework without quantum evolution. We assume the strong coupling constant much smaller than one. Due to the heavy mass and colorless nature of Higgs particle, final state interactions are absent in our calculation. In order to treat the two nuclei dynamically symmetric, we use the Coulomb gauge which gives the appropriate light cone gauge for each nucleus. To further eliminate initial state interactions we choose specific prescriptions in the light cone propagators. We start the calculation from only two nucleons in each nucleus and then demonstrate how to generalize the calculation to higher orders diagrammatically. We simplify the diagrams by the Slavnov-Taylor-Ward identities. The resulting cross section is factorized into a product of two Weizsacker-Williams gluon distributions of the two nuclei when the transverse momentum of the produced scalar particle is around the saturation momentum. To our knowledge this is the first process where an exact analytic formula has been formed for a physical process, involving momenta on the order of the saturation momentum, in nucleus-nucleus collisions in the quasi-classical approximation. Since we have performed the calculation in an unconventional gauge choice, we further confirm our results in Feynman gauge where the Weizsacker-Williams gluon distribution is interpreted as a transverse momentum broadening of a hard gluons traversing a nuclear medium. The transverse momentum factorization manifests itself in light cone gauge but not so clearly in Feynman gauge. In saturation physics there are two different unintegrated gluon distributions usually encountered in the literature: the Weizsacker-Williams gluon distribution and the dipole gluon distribution. The first gluon distribution is constructed by solving classical Yang-Mills equation of motion in the Mc

  7. Identification of a novel starfish neuropeptide that acts as a muscle relaxant.

    PubMed

    Kim, Chan-Hee; Kim, Eun Jung; Go, Hye-Jin; Oh, Hye Young; Lin, Ming; Elphick, Maurice R; Park, Nam Gyu

    2016-04-01

    Neuropeptides that act as muscle relaxants have been identified in chordates and protostomian invertebrates but little is known about the molecular identity of neuropeptides that act as muscle relaxants in deuterostomian invertebrates (e.g. echinoderms) that are 'evolutionary intermediates' of chordates and protostomes. Here, we have used the apical muscle of the starfish Patiria pectinifera to assay for myorelaxants in extracts of this species. A hexadecapeptide with the amino acid sequence Phe-Gly-Lys-Gly-Gly-Ala-Tyr-Asp-Pro-Leu-Ser-Ala-Gly-Phe-Thr-Asp was identified and designated starfish myorelaxant peptide (SMP). Cloning and sequencing of a cDNA encoding the SMP precursor protein revealed that it comprises 12 copies of SMP as well as 3 peptides (7 copies in total) that are structurally related to SMP. Analysis of the expression of SMP precursor transcripts in P. pectinifera using qPCR revealed the highest expression in the radial nerve cords and lower expression levels in a range of neuromuscular tissues, including the apical muscle, tube feet and cardiac stomach. Consistent with these findings, SMP also caused relaxation of tube foot and cardiac stomach preparations. Furthermore, SMP caused relaxation of apical muscle preparations from another starfish species - Asterias amurensis. Collectively, these data indicate that SMP has a general physiological role as a muscle relaxant in starfish. Interestingly, comparison of the sequence of the SMP precursor with known neuropeptide precursors revealed that SMP belongs to a bilaterian family of neuropeptides that include molluscan pedal peptides (PP) and arthropodan orcokinins (OK). This is the first study to determine the function of a PP/OK-type peptide in a deuterostome. Pedal peptide/orcokinin (PP/OK)-type peptides are a family of structurally related neuropeptides that were first identified and functionally characterised in protostomian invertebrates. Here, we report the discovery of starfish myorelaxant

  8. Neuropeptide Y stimulates feeding but inhibits sexual behavior in rats.

    PubMed

    Clark, J T; Kalra, P S; Kalra, S P

    1985-12-01

    The effects of neuropeptide Y (NPY), a tyrosine-rich peptide found in the rat brain, on feeding and sexual behavior were studied in male and female rats. Intraventricular (ivt) injections of NPY during the final hours of the light period induced feeding in a dose-related manner. While the lowest dose tested (0.02 nM) was without effect, higher doses (0.12, 0.47, 2.3 nM) uniformly elicited feeding with a latency of about 15 min in male rats. With the most effective dose, 0.47 nM, the increased food intake was due to an increased local eating rate. In contrast, the pattern of feeding behavior after a related peptide, rat pancreatic polypeptide (rPP), was quite different and less impressive. During the first hour, only one ivt dose of rPP (0.45 nM) evoked an increase in food intake, due to an increased time spent eating. Further, the effects of NPY on food intake were greater during the nocturnal period. Interestingly, increased food intake in nocturnal tests (4 h) was due solely to augmented intake during the first 60 min after ivt administration. In mating tests, initiated 2 h after the onset of darkness and 10 min after ivt administration of peptide, all but the lowest dose of NPY (0.01 nM) drastically suppressed ejaculatory behavior. Most rats treated with higher doses of NPY (0.02, 0.12, or 0.47 nM) mounted and intromitted only a few times before the cessation of sexual activity, and elongated latencies to the initial mount and intromission were observed. In contrast to the dramatic NPY-induced suppression of ejaculatory behavior, rPP (0.11 and 0.45 nM) was without effect on copulatory behavior. To substantiate further that the impairment of sexual behavior seen in NPY-treated rats was not due to an attenuated sexual ability, an additional experiment was performed. Penile reflexes, including erection, were monitored 10 min after ivt injection of NPY (0.12 nM), rPP (0.11 nM), or saline. No effect of NPY or rPP was observed on the proportion of rats showing

  9. Conservation of the function counts: homologous neurons express sequence-related neuropeptides that originate from different genes.

    PubMed

    Neupert, Susanne; Huetteroth, Wolf; Schachtner, Joachim; Predel, Reinhard

    2009-11-01

    By means of single-cell matrix assisted laser desorption/ionization time-of-flight mass spectrometry, we analysed neuropeptide expression in all FXPRLamide/pheromone biosynthesis activating neuropeptide synthesizing neurons of the adult tobacco hawk moth, Manduca sexta. Mass spectra clearly suggest a completely identical processing of the pheromone biosynthesis activating neuropeptide-precursor in the mandibular, maxillary and labial neuromeres of the subesophageal ganglion. Only in the pban-neurons of the labial neuromere, products of two neuropeptide genes, namely the pban-gene and the capa-gene, were detected. Both of these genes expressed, amongst others, sequence-related neuropeptides (extended WFGPRLamides). We speculate that the expression of the two neuropeptide genes is a plesiomorph character typical of moths. A detailed examination of the neuroanatomy and the peptidome of the (two) pban-neurons in the labial neuromere of moths with homologous neurons of different insects indicates a strong conservation of the function of this neuroendocrine system. In other insects, however, the labial neurons either express products of the fxprl-gene or products of the capa-gene. The processing of the respective genes is reduced to extended WFGPRLamides in each case and yields a unique peptidome in the labial cells. Thus, sequence-related messenger molecules are always produced in these cells and it seems that the respective neurons recruited different neuropeptide genes for this motif. PMID:19712058

  10. The effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women

    PubMed Central

    Khoshdel, Abolfazl; Kheiri, Soleiman; Nasiri, Jafar; Tehran, Hoda Ahmari; Heidarian, Esfandiar

    2014-01-01

    Background: Many pregnant Muslim women choose to fast during Ramadan every year worldwide. This study aimed to examine the effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women and find whether fasting during pregnancy could have a negative effect on the health of mothers and fetuses. Methods: This cross-sectional study was conducted on 39 healthy volunteer fasting pregnant women. Serum leptin, neuropeptide Y, insulin levels, body mass index and weight were measured five times on 0, 7th, 14th and 28th days of Ramadan and on the 14th day post-Ramadan. The data were analyzed by SPSS software (version 11.5) using repeated measures ANOVA to find whether any changes occurred in the variables of interest during the study, and Pearson correlation coefficient was used to examine the relations among the variables. Results: A significant change in fasting blood sugar, neuropeptide Y and leptin was observed during the study (p< 0.05). Fasting blood sugar decreased significantly during Ramadan and increased after Ramadan, with the lowest value at the end of Ramadan. Neuropeptide Y increased both during Ramadan and two weeks after Ramadan. Also, leptin decreased significantly two weeks after Ramadan compared to the end of Ramadan. No significant change was observed in insulin level during the study (p>0.05). Conclusion: The result of this study revealed the important role of leptin and neuropeptide Y in the long term regulation of energy balance in pregnant women with chronic diurnal fasting, and it further revealed that Ramadan fasting did not significantly change the serum insulin level. PMID:25664293

  11. Dynamical nucleus-nucleus potential at short distances

    SciTech Connect

    Jiang Yongying; Wang Ning; Li Zhuxia; Scheid, Werner

    2010-04-15

    The dynamical nucleus-nucleus potentials for fusion reactions {sup 40}Ca+{sup 40}Ca, {sup 48}Ca+{sup 208}Pb, and {sup 126}Sn+{sup 130}Te are studied with the improved quantum molecular dynamics model together with the extended Thomas-Fermi approximation for the kinetic energies of nuclei. The obtained fusion barrier for {sup 40}Ca+{sup 40}Ca is in good agreement with the extracted fusion barrier from the measured fusion excitation function, and the depths of the fusion pockets are close to the results of time-dependent Hartree-Fock calculations. The energy dependence of the fusion barrier is also investigated. The fusion pocket becomes shallow for a heavy fusion system and almost disappears for heavy nearly symmetric systems, and the obtained potential at short distances is higher than the adiabatic potential.

  12. Azimuthal correlation and collective behavior in nucleus-nucleus collisions

    SciTech Connect

    Mali, P.; Mukhopadhyay, A. Sarkar, S.; Singh, G.

    2015-03-15

    Various flow effects of nuclear and hadronic origin are investigated in nucleus-nucleus collisions. Nuclear emulsion data collected from {sup 84}Kr + Ag/Br interaction at an incident energy of 1.52 GeV per nucleon and from {sup 28}Si + Ag/Br interaction at an incident energy of 14.5 GeV per nucleon are used in the investigation. The transverse momentum distribution and the flow angle analysis show that collective behavior, like a bounce-off effect of the projectile spectators and a sidesplash effect of the target spectators, are present in our event samples. From an azimuthal angle analysis of the data we also see a direct flow of the projectile fragments and of the produced charged particles. On the other hand, for both data samples the target fragments exhibit a reverse flow, while the projectile fragments exhibit an elliptic flow. Relevant flow parameters are measured.

  13. Analysis of relativistic nucleus-nucleus interactions in emulsion chambers

    NASA Technical Reports Server (NTRS)

    Mcguire, Stephen C.

    1987-01-01

    The development of a computer-assisted method is reported for the determination of the angular distribution data for secondary particles produced in relativistic nucleus-nucleus collisions in emulsions. The method is applied to emulsion detectors that were placed in a constant, uniform magnetic field and exposed to beams of 60 and 200 GeV/nucleon O-16 ions at the Super Proton Synchrotron (SPS) of the European Center for Nuclear Research (CERN). Linear regression analysis is used to determine the azimuthal and polar emission angles from measured track coordinate data. The software, written in BASIC, is designed to be machine independent, and adaptable to an automated system for acquiring the track coordinates. The fitting algorithm is deterministic, and takes into account the experimental uncertainty in the measured points. Further, a procedure for using the track data to estimate the linear momenta of the charged particles observed in the detectors is included.

  14. Single nucleon emission in relativistic nucleus-nucleus reactions

    NASA Technical Reports Server (NTRS)

    Norbury, John W.; Townsend, Lawrence W.

    1992-01-01

    Significant discrepancies between theory and experiment have previously been noted for nucleon emission via electromagnetic processes in relativistic nucleus-nucleus collisions. The present work investigates the hypothesis that these discrepancies have arisen due to uncertainties about how to deduce the experimental electromagnetic cross section from the total measured cross section. An optical-model calculation of single neutron removal is added to electromagnetic cross sections and compared to the total experimental cross sections. Good agreement is found thereby resolving some of the earlier noted discrepancies. A detailed comparison to the recent work of Benesh, Cook, and Vary is made for both the impact parameter and the nuclear cross section. Good agreement is obtained giving an independent confirmation of the parameterized formulas developed by those authors.

  15. Hummingbird Comet Nucleus Analysis Mission

    NASA Technical Reports Server (NTRS)

    Kojiro, Daniel; Carle, Glenn C.; Lasher, Larry E.

    2000-01-01

    Hummingbird is a highly focused scientific mission, proposed to NASA s Discovery Program, designed to address the highest priority questions in cometary science-that of the chemical composition of the cometary nucleus. After rendezvous with the comet, Hummingbird would first methodically image and map the comet, then collect and analyze dust, ice and gases from the cometary atmosphere to enrich characterization of the comet and support landing site selection. Then, like its namesake, Hummingbird would carefully descend to a pre-selected surface site obtaining a high-resolution image, gather a surface material sample, acquire surface temperature and then immediately return to orbit for detailed chemical and elemental analyses followed by a high resolution post-sampling image of the site. Hummingbird s analytical laboratory contains instrumentation for a comprehensive molecular and elemental analysis of the cometary nucleus as well as an innovative surface sample acquisition device.

  16. Transient expression of somatostatin messenger RNA and peptide in the hypoglossal nucleus of the neonatal rat.

    PubMed

    Seroogy, K B; Bayliss, D A; Szymeczek, C L; Hökfelt, T; Millhorn, D E

    1991-06-21

    The postnatal developmental expression of somatostatin mRNA and peptide in the rat hypoglossal nucleus was analyzed using immunocytochemical and in situ hybridization techniques. Both the neuropeptide and its cognate mRNA were found to be transiently present within a subpopulation of hypoglossal motoneurons during the neonatal period. At the day of birth, a large population of perikarya situated in caudal, ventral regions of the hypoglossal nucleus expressed somatostatin. By postnatal day 7, the number of hypoglossal somata which expressed somatostatin had diminished considerably, and by 2 weeks postnatal, only few such cell bodies were found. By 3-4 weeks postnatal, somatostatin peptide- and mRNA-containing hypoglossal motoneurons were rarely observed, and in the adult, they were never detected, despite the use of colchicine. A double-labeling co-localization technique was used to demonstrate that somatostatin, when present perinatally, always coexisted with calcitonin gene-related peptide in hypoglossal motoneurons. The latter peptide, in contrast to somatostatin, was expressed in large numbers of somata throughout the entire hypoglossal nucleus and persisted within the motoneurons throughout development into adulthood. These results demonstrate that somatostatin is transiently expressed in motoneurons of the caudal, ventral tier of the hypoglossal nucleus in the neonatal rat. The developmental disappearance of somatostatin is most likely not due to cell death; hypoglossal somata continue to express calcitonin gene-related peptide, with which somatostatin coexisted perinatally, a high levels throughout development. Thus, it appears that the regulation of somatostatin expression in hypoglossal neurons occurs at the level of gene transcription or mRNA stability/degradation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1680035

  17. Neuropeptides: metabolism to bioactive fragments and the pharmacology of their receptors.

    PubMed

    Hallberg, Mathias

    2015-05-01

    The proteolytic processing of neuropeptides has an important regulatory function and the peptide fragments resulting from the enzymatic degradation often exert essential physiological roles. The proteolytic processing generates, not only biologically inactive fragments, but also bioactive fragments that modulate or even counteract the response of their parent peptides. Frequently, these peptide fragments interact with receptors that are not recognized by the parent peptides. This review discusses tachykinins, opioid peptides, angiotensins, bradykinins, and neuropeptide Y that are present in the central nervous system and their processing to bioactive degradation products. These well-known neuropeptide systems have been selected since they provide illustrative examples that proteolytic degradation of parent peptides can lead to bioactive metabolites with different biological activities as compared to their parent peptides. For example, substance P, dynorphin A, angiotensin I and II, bradykinin, and neuropeptide Y are all degraded to bioactive fragments with pharmacological profiles that differ considerably from those of the parent peptides. The review discusses a selection of the large number of drug-like molecules that act as agonists or antagonists at receptors of neuropeptides. It focuses in particular on the efforts to identify selective drug-like agonists and antagonists mimicking the effects of the endogenous peptide fragments formed. As exemplified in this review, many common neuropeptides are degraded to a variety of smaller fragments but many of the fragments generated have not yet been examined in detail with regard to their potential biological activities. Since these bioactive fragments contain a small number of amino acid residues, they provide an ideal starting point for the development of drug-like substances with ability to mimic the effects of the degradation products. Thus, these substances could provide a rich source of new pharmaceuticals

  18. Neuropeptides in Heteroptera: Identification of allatotropin-related peptide and tachykinin-related peptides using MALDI-TOF mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, the peptidomic analysis of neuropeptides from the retrocerebral complex and abdominal perisympathetic organs of polyphagous stinkbugs (Pentatomidae) revealed the group-specific sequences of pyrokinins, CAPA peptides (CAPA-periviscerokinins/PVKs and CAPA-pyrokinin), myosuppressin, corazonin...

  19. Neuropeptide imaging on an LTQ with vMALDI source: The complete `all-in-one' peptidome analysis

    NASA Astrophysics Data System (ADS)

    Verhaert, Peter D.; Conaway, Maria C. Prieto; Pekar, Tonya M.; Miller, Ken

    2007-02-01

    Direct tissue imaging was performed on dissected insect tissue using a MALDI ion trap to visualize endogenous neuropeptides. Coupling tissue imaging to tandem MSn allows for the identification of previously known species and the ability to identify new ones by de novo sequencing, as searchable databases for insects are sparse. Direct tissue imaging is an attractive technique for the study of neuropeptides as minimal sample preparation is required prior to mass spectrometry. We successfully identified neuropeptides present in the corpora cardiaca and allata of Acheta domesticus (the house cricket). Diagnostic fragments at low m/z were used to distinguish between lipids and neuropeptides. The distribution of peptides appears to be more differentially localized than that of phospholipids, which seem to be more evenly distributed within the tissue.

  20. Expression of Exocytosis Proteins in Rat Supraoptic Nucleus Neurones

    PubMed Central

    Tobin, V.; Schwab, Y.; Lelos, N.; Onaka, T.; Pittman, Q. J.; Ludwig, M.

    2012-01-01

    In magnocellular neurones of the supraoptic nucleus (SON), the neuropeptides vasopressin and oxytocin are synthesised and packaged into large dense-cored vesicles (LDCVs). These vesicles undergo regulated exocytosis from nerve terminals in the posterior pituitary gland and from somata/dendrites in the SON. Regulated exocytosis of LDCVs is considered to involve the soluble N-ethylmaleimide sensitive fusion protein attachment protein receptor (SNARE) complex [comprising vesicle associated membrane protein 2 (VAMP-2), syntaxin-1 and soluble N-ethylmaleimide attachment protein-25 (SNAP-25)] and regulatory proteins [such as synaptotagmin-1, munc-18 and Ca2+-dependent activator protein for secretion (CAPS-1)]. Using fluorescent immunocytochemistry and confocal microscopy, in both oxytocin and vasopressin neurones, we observed VAMP-2, SNAP-25 and syntaxin-1-immunoreactivity in axon terminals. The somata and dendrites contained syntaxin-1 and other regulatory exocytosis proteins, including munc-18 and CAPS-1. However, the distribution of VAMP-2 and synaptotagmin-1 in the SON was limited to putative pre-synaptic contacts because they co-localised with synaptophysin (synaptic vesicle marker) and had no co-localisation with either oxytocin or vasopressin. SNAP-25 immunoreactivity in the SON was limited to glial cell processes and was not detected in oxytocin or vasopressin somata/dendrites. The present results indicate differences in the expression and localisation of exocytosis proteins between the axon terminals and somata/dendritic compartment. The absence of VAMP-2 and SNAP-25 immunoreactivity from the somata/dendrites suggests that there might be different SNARE protein isoforms expressed in these compartments. Alternatively, exocytosis of LDCVs from somata/dendrites may use a different mechanism from that described by the SNARE complex theory. PMID:21988098

  1. Transcriptome and Peptidome Characterisation of the Main Neuropeptides and Peptidic Hormones of a Euphausiid: The Ice Krill, Euphausia crystallorophias

    PubMed Central

    Toullec, Jean-Yves; Corre, Erwan; Bernay, Benoît; Thorne, Michael A. S.; Cascella, Kévin; Ollivaux, Céline; Henry, Joël; Clark, Melody S.

    2013-01-01

    Background The Ice krill, Euphausia crystallorophias is one of the species at the base of the Southern Ocean food chain. Given their significant contribution to the biomass of the Southern Ocean, it is vitally important to gain a better understanding of their physiology and, in particular, anticipate their responses to climate change effects in the warming seas around Antarctica. Methodology/Principal Findings Illumina sequencing was used to produce a transcriptome of the ice krill. Analysis of the assembled contigs via two different methods, produced 36 new pre-pro-peptides, coding for 61 neuropeptides or peptide hormones belonging to the following families: Allatostatins (A, B et C), Bursicon (α and β), Crustacean Hyperglycemic Hormones (CHH and MIH/VIHs), Crustacean Cardioactive Peptide (CCAP), Corazonin, Diuretic Hormones (DH), the Eclosion Hormone (EH), Neuroparsin, Neuropeptide F (NPF), small Neuropeptide F (sNPF), Pigment Dispersing Hormone (PDH), Red Pigment Concentrating Hormone (RPCH) and finally Tachykinin. LC/MS/MS proteomics was also carried out on eyestalk extracts, which are the major site of neuropeptide synthesis in decapod crustaceans. Results confirmed the presence of six neuropeptides and six precursor-related peptides previously identified in the transcriptome analyses. Conclusions This study represents the first comprehensive analysis of neuropeptide hormones in a Eucarida non-decapod Malacostraca, several of which are described for the first time in a non-decapod crustacean. Additionally, there is a potential expansion of PDH and Neuropeptide F family members, which may reflect certain life history traits such as circadian rhythms associated with diurnal migrations and also the confirmation via mass spectrometry of several novel pre-pro-peptides, of unknown function. Knowledge of these essential hormones provides a vital framework for understanding the physiological response of this key Southern Ocean species to climate change and provides

  2. Transcriptomic Analysis of Neuropeptides and Peptide Hormones in the Barnacle Balanus amphitrite: Evidence of Roles in Larval Settlement

    PubMed Central

    Yan, Xing-Cheng; Chen, Zhang-Fan; Sun, Jin; Matsumura, Kiyotaka; Wu, Rudolf S. S.; Qian, Pei-Yuan

    2012-01-01

    The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in this study shall

  3. Photoproduction of lepton pairs in proton-nucleus and nucleus-nucleus collisions at RHIC and LHC energies

    SciTech Connect

    Moreira, B. D.; Goncalves, V. P.; De Santana Amaral, J. T.

    2013-03-25

    In this contribution we study coherent interactions as a probe of the nonlinear effects in the Quantum Electrodynamics (QED). In particular, we study the multiphoton effects in the production of leptons pairs for proton-nucleus and nucleus-nucleus collisions for heavy nuclei. In the proton-nucleus we assume the ultrarelativistic proton as a source of photons and estimate the photoproduction of lepton pairs on nuclei at RHIC and LHC energies considering the multiphoton effects associated to multiple rescattering of the projectile photon on the proton of the nucleus. In nucleus - nucleus colllisions we consider the two nuclei as a source of photons. As each scattering contributes with a factor {alpha}Z to the cross section, this contribution must be taken into account for heavy nuclei. We consider the Coulomb corrections to calculate themultiple scatterings and estimate the total cross section for muon and tau pair production in proton-nucleus and nucleus-nucleus collisions at RHIC and LHC energies.

  4. Deficiency of prohormone convertase dPC2 (AMONTILLADO) results in impaired production of bioactive neuropeptide hormones in Drosophila.

    PubMed

    Wegener, Christian; Herbert, Henrik; Kahnt, Jörg; Bender, Michael; Rhea, Jeanne M

    2011-08-01

    Peptide hormones synthesized by secretory neurons in the CNS are important regulators of physiology, behavior, and development. Like other neuropeptides, they are synthesized from larger precursor molecules by a specific set of enzymes. Using a combination of neurogenetics, immunostainings, and direct mass spectrometric profiling, we show that the presence of Drosophila prohormone convertase 2 encoded by the gene amontillado (amon) is a prerequisite for the proper processing of neuropeptide hormones from the major neurohemal organs of the CNS. A loss of amon correlates with a loss of neuropeptide hormone signals from the larval ring gland and perisympathetic organs. Neuropeptide hormone signals were still detectable in the adult corpora cardiaca of older amon-deficient flies which were amon heat-shock-rescued until eclosion. A semiquantification by direct peptide profiling using stable isotopic standards showed, however, that their neuropeptide hormone levels are strongly reduced. Targeted expression of GFP under the control of amon regulatory regions revealed a co-localization with the investigated peptide hormones in secretory neurons of the brain and ventral nerve cord. The lack of AMON activity resulted in a deficiency of L3 larva to enter the wandering phase. In conclusion, our findings provide the first direct evidence that AMON is a key enzyme in the production of neuropeptides in the fruitfly. PMID:21138435

  5. Neuropeptidome of the Cephalopod Sepia officinalis: Identification, Tissue Mapping, and Expression Pattern of Neuropeptides and Neurohormones during Egg Laying.

    PubMed

    Zatylny-Gaudin, Céline; Cornet, Valérie; Leduc, Alexandre; Zanuttini, Bruno; Corre, Erwan; Le Corguillé, Gildas; Bernay, Benoît; Garderes, Johan; Kraut, Alexandra; Couté, Yohan; Henry, Joël

    2016-01-01

    Cephalopods exhibit a wide variety of behaviors such as prey capture, communication, camouflage, and reproduction thanks to a complex central nervous system (CNS) divided into several functional lobes that express a wide range of neuropeptides involved in the modulation of behaviors and physiological mechanisms associated with the main stages of their life cycle. This work focuses on the neuropeptidome expressed during egg-laying through de novo construction of the CNS transcriptome using an RNAseq approach (Illumina sequencing). Then, we completed the in silico analysis of the transcriptome by characterizing and tissue-mapping neuropeptides by mass spectrometry. To identify neuropeptides involved in the egg-laying process, we determined (1) the neuropeptide contents of the neurohemal area, hemolymph (blood), and nerve endings in mature females and (2) the expression levels of these peptides. Among the 38 neuropeptide families identified from 55 transcripts, 30 were described for the first time in Sepia officinalis, 5 were described for the first time in the animal kingdom, and 14 were strongly overexpressed in egg-laying females as compared with mature males. Mass spectrometry screening of hemolymph and nerve ending contents allowed us to clarify the status of many neuropeptides, that is, to determine whether they were neuromodulators or neurohormones. PMID:26632866

  6. Neuropeptides in the cerebral ganglia of the mud crab, Scylla paramamosain: transcriptomic analysis and expression profiles during vitellogenesis

    PubMed Central

    Bao, Chenchang; Yang, Yanan; Huang, Huiyang; Ye, Haihui

    2015-01-01

    Neuropeptides play a critical role in regulating animal reproduction. In vertebrates, GnRH, GnIH and kisspeptin are the key neuropeptide hormones of the reproductive axis, however, the reproductive axis for invertebrates is vague. Knowledge on ovarian development of the mud crab, Scylla paramamosain, is critical for aquaculture and resources management of the commercially important species. This study employed Illumina sequencing, reverse transcription-polymerase chain reaction and quantitative real-time PCR techniques to identify neuropeptides that may be involved in ovarian development of S. paramamosain. A total of 32 neuropeptide transcripts from two dozen neuropeptide families, 100 distinct mature peptides were predicted from the transcriptome data of female S. paramamosain cerebral ganglia. Among them, two families, i.e. GSEFLamide and WXXXRamide, were first identified from the cerebral ganglia of crustaceans. Of these neuropeptides, 21 transcripts of interest were selected for further confirmation and all of them were detected in the cerebral ganglia, as well as in other nervous tissues and the ovary. Most of them also had differential expression in the cerebral ganglia during various vitellogenic stages, suggesting their likely involvement in regulating vitellogenesis and ovarian maturation. Overall, these findings provide an important basis for subsequent studies on peptide function in reproduction of S. paramamosain. PMID:26592767

  7. Expression and distribution of neuropeptides in the nervous system of the crab Carcinus maenas and their roles in environmental stress.

    PubMed

    Zhang, Yuzhuo; Buchberger, Amanda; Muthuvel, Gajanthan; Li, Lingjun

    2015-12-01

    Environmental fluctuations, such as salinity, impose serious challenges to marine animal survival. Neuropeptides, signaling molecules involved in the regulation process, and the dynamic changes of their full complement in the stress response have yet to be investigated. Here, a MALDI-MS-based stable isotope labeling quantitation strategy was used to investigate the relationship between neuropeptide expression and adaptability of Carcinus maenas to various salinity levels, including high (60 parts per thousand [p.p.t.]) and low (0 p.p.t.) salinity, in both the crustacean pericardial organ (PO) and brain. Moreover, a high salinity stress time course study was conducted. MS imaging (MSI) of neuropeptide localization in C. maenas PO was also performed. As a result of salinity stress, multiple neuropeptide families exhibited changes in their relative abundances, including RFamides (e.g. APQGNFLRFamide), RYamides (e.g. SSFRVGGSRYamide), B-type allatostatins (AST-B; e.g. VPNDWAHFRGSWamide), and orcokinins (e.g. NFDEIDRSSFGFV). The MSI data revealed distribution differences in several neuropeptides (e.g. SGFYANRYamide) between color morphs, but salinity stress appeared to not have a major effect on the localization of the neuropeptides. PMID:26475201

  8. In silico cloning of genes encoding neuropeptides, neurohormones and their putative G-protein coupled receptors in a spider mite.

    PubMed

    Veenstra, Jan A; Rombauts, Stephane; Grbić, Miodrag

    2012-04-01

    The genome of the spider mite was prospected for the presence of genes coding neuropeptides, neurohormones and their putative G-protein coupled receptors. Fifty one candidate genes were found to encode neuropeptides or neurohormones. These include all known insect neuropeptides and neurohormones, with the exception of sulfakinin, corazonin, neuroparsin and PTTH. True orthologs of adipokinetic hormone (AKH) were neither found, but there are three genes encoding peptides similar in structure to both AKH and the AKH-corazonin-related peptide. We were also unable to identify the precursors for pigment dispersing factor (PDF) or the recently discovered trissin. However, the spider mite probably does have such genes, as we found their putative receptors. A novel arthropod neuropeptide gene was identified that shows similarity to previously described molluscan neuropeptide genes and was called EFLamide. A total of 65 putative neuropeptide GPCR genes were also identified, of these 58 belong to the A-family and 7 to the B-family. Phylogenetic analysis showed that 50 of them are closely related to insect GPCRs, which allowed the identification of their putative ligand in 39 cases with varying degrees of certainty. Other spider mite GPCRs however have no identifiable orthologs in the genomes of the four holometabolous insect species best analyzed. Whereas some of the latter have orthologs in hemimetabolous insect species, crustaceans or ticks, for others such arthropod homologs are currently unknown. PMID:22214827

  9. Unilateral lesion increases oestrogen receptor α expression in the intact side of the ventromedial hypothalamic nucleus in ovariectomised rats.

    PubMed

    Shimogawa, Y; Maekawa, F; Yamanouchi, K

    2014-04-01

    To determine the relationship between the right and left sides of the ventrolateral ventromedial hypothalamic nucleus (vlVMN) in regulating the expression of oestrogen receptor (ER)α, the unilateral vlVMN was lesioned and the number of ERα-immunoreactive cells and the ERα mRNA level in the intact side of the vlVMN and arcuate nucleus (ARC) were measured in ovariectomised rats. Twenty-four hours after lesioning, brain samples were collected for analysis of ERα expression by immunohistochemistry and the real-time reverse transcriptase-polymerase chain reaction. The number of ERα-immunoreactive cells in the intact side of the vlVMN but not the ARC in the unilateral lesioned group was significantly higher than that in the control or sham-lesioned group. Expression levels of ERα mRNA in the intact side of the vlVMN but not the ARC in unilateral lesioned rats were significantly higher than those in the sham-lesioned group. Of transcript variants with alternative 5'-untranslated regions (0S, 0N, 0, 0T and E1), the ERα 0 transcript level was significantly increased. These results indicate that unilateral damage of vlVMN induces an increase in ERα in the intact side by increasing ERα transcription in a promoter-specific manner. The findings also suggest the existence of new neuroendocrine control system between the right and left sides for the expression of ERα in the vlVMN. PMID:24629021

  10. Hormones, hormonal agents, and neuropeptides involved in the neuroendocrine regulation of sleep in humans.

    PubMed

    Kotronoulas, Grigorios; Stamatakis, Antonios; Stylianopoulou, Fotini

    2009-01-01

    Sleep is an essential ubiquitous biological process, a periodical state of quiescence in which there is minimal processing of sensory information and no interaction with conspecifics or the environment. Despite relevant research on sleep structure and testing of numerous endogenous sleep-affecting chemicals, questions as to the precise mechanisms and functions of sleep remain without satisfactory responses. The purpose of this review is to report on current evidence as regards the effect of several endogenous and exogenous hormones, hormonal agents, and neuropeptides on sleep onset or wake process, when administered in humans in specific doses and via different routes. The actions of several peptides are presented in detail. Some of them (growth hormone releasing hormone, ghrelin, galanin, neuropeptide Y) seem to promote sleep, whereas others (corticotropin, somatostatin) impair its continuity. PMID:20045796

  11. CD and 31P NMR studies of tachykinin and MSH neuropeptides in SDS and DPC micelles

    NASA Astrophysics Data System (ADS)

    Schneider, Sydney C.; Brown, Taylor C.; Gonzalez, Javier D.; Levonyak, Nicholas S.; Rush, Lydia A.; Cremeens, Matthew E.

    2016-02-01

    Secondary structural characteristics of substance P (SP), neurokinin A (NKA), neurokinin B (NKB), α-melanocyte stimulating hormone peptide (α-MSH), γ1-MSH, γ2-MSH, and melittin were evaluated with circular dichroism in phosphite buffer, DPC micelles, and SDS micelles. CD spectral properties of γ1-MSH and γ2-MSH as well as 31P NMR of DPC micelles with all the peptides are reported for the first time. Although, a trend in the neuropeptide/micelle CD data appears to show increased α-helix content for the tachykinin peptides (SP, NKA, NKB) and increased β-sheet content for the MSH peptides (α-MSH, γ1-MSH, γ2-MSH) with increasing peptide charge, the lack of perturbed 31P NMR signals for all neuropeptides could suggest that the reported antimicrobial activity of SP and α-MSH might not be related to a membrane disruption mode of action.

  12. Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release

    PubMed Central

    Chatzigeorgiou, Marios; Hu, Zhitao; Schafer, William R.; Kaplan, Joshua M.

    2015-01-01

    C. elegans undergoes periods of behavioral quiescence during larval molts (termed lethargus) and as adults. Little is known about the circuit mechanisms that establish these quiescent states. Lethargus and adult locomotion quiescence is dramatically reduced in mutants lacking the neuropeptide receptor NPR-1. Here, we show that the aroused locomotion of npr-1 mutants results from the exaggerated activity in multiple classes of sensory neurons, including nociceptive (ASH), touch sensitive (ALM and PLM), and stretch sensing (DVA) neurons. These sensory neurons accelerate locomotion via both neuropeptide and glutamate release. The relative contribution of these sensory neurons to arousal differs between larval molts and adults. Our results suggest that a broad network of sensory neurons dictates transitions between aroused and quiescent behavioral states. PMID:26154367

  13. New roles of a neuropeptide cortistatin in the immune system and cancer.

    PubMed

    Li, Min; Yan, Shaoyu; Fisher, William E; Chen, Changyi; Yao, Qizhi

    2005-03-01

    Cortistatin (CST) is a neuropeptide that strongly resembles somatostatin (SS) structurally and functionally. CST binds to all five SS receptors (SSTR1-SSTR5) with high affinity and exerts its function mainly through SSTRs. Despite many similar functions between these two neuropeptides, they are products of different genes. Recently, some distinct functions and receptor usage of CST have been reported. Some of the interesting functions of CST were not found with SS. Therefore CST could have potential new roles in an ex-neuronal system that regulates immune responses as well as other cellular functions in the body. In this review, we discuss the new functions of CST in the immune system, cancer pathogenesis, and possible CST-specific receptors. PMID:15696397

  14. Identification of new members of the (short) neuropeptide F family in locusts and Caenorhabditis elegans.

    PubMed

    Clynen, Elke; Husson, Steven J; Schoofs, Liliane

    2009-04-01

    Both the long and short neuropeptides F (NPF) represent important families of invertebrate neuropeptides that have been implicated in the regulation of reproduction and feeding behavior. In the present study, two short NPFs (SNRSPS(L/I)R(L/I)RFamide and SPS(L/I)R(L/I)RFamide) were de novo sequenced by mass spectrometry in two major pest insects, the desert locust Schistocerca gregaria and the African migratory locust Locusta migratoria. They are two of the most widespread peptides in the locust neuroendocrine system. A peptide that was previously reported to accelerate egg development in S. gregaria is shown to represent a truncated form of long NPF. This peptide is most likely derived by a novel processing mechanism involving cleavage at RY. In addition, an NPF peptide from the nematode Caenorhabditis elegans was isolated and sequenced by tandem mass spectrometry. PMID:19456328

  15. Identification of the first neuropeptides from the enigmatic hexapod order Protura.

    PubMed

    Christie, Andrew E; Chi, Megan

    2015-12-01

    The Hexapoda consists of two classes, the Entognatha and the Insecta, with the former group considered basal to the latter. The Protura is a basal order within the Entognatha, the members of which are minute soil dwellers first identified in the early 20th century. Recently, a transcriptome shotgun assembly (TSA) was generated for the proturan Acerentomon sp., providing the first significant molecular resource for this enigmatic hexapod order. As part of an ongoing effort to predict peptidomes for little studied members of the Arthropoda, we have mined this TSA dataset for transcripts encoding putative neuropeptide precursors and predicted the structures of mature peptides from the deduced proteins. Forty-seven peptide-encoding transcripts were mined from the Acerentomon TSA dataset, with 202 distinct peptides predicted from them. The peptides identified included isoforms of adipokinetic hormone, adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin B, allatostatin C, allatotropin, bursicon α, bursicon β, CCHamide, corazonin, crustacean cardioactive peptide, crustacean hyperglycemic hormone/ion transport peptide, diuretic hormone 31, diuretic hormone 44, ecdysis-triggering hormone, eclosion hormone, FMRFamide-like peptide, GSEFLamide, insulin-like peptide, intocin, leucokinin, myosuppressin, neuropeptide F, orcokinin, proctolin, pyrokinin, RYamide, short neuropeptide F, SIFamide, sulfakinin and tachykinin-related peptide; these are the first neuropeptides described from any proturan. Comparison of the Acerentomon precursors and mature peptides with those from other arthropods revealed features characteristic of both the insects and the crustaceans, which is consistent with the hypothesized phylogenetic position of the Protura within the Pancrustacea, i.e. at or near the point of divergence of the hexapods from the crustaceans. PMID:26055220

  16. Control of sleep-to-wake transitions via fast aminoacid and slow neuropeptide transmission

    PubMed Central

    Mosqueiro, Thiago; de Lecea, Luis; Huerta, Ramon

    2014-01-01

    The Locus Coeruleus (LC) modulates cortical, subcortical, cerebellar, brainstem and spinal cord circuits and it expresses receptors for neuromodulators that operate in a time scale of several seconds. Evidences from anatomical, electrophysiological and optogenetic experiments have shown that LC neurons receive input from a group of neurons called Hypocretins (HCRTs) that release a neuropeptide called hypocretin. It is less known how these two groups of neurons can be coregulated using GABAergic neurons. Since the time scales of GABAA inhibition is several orders of magnitude faster than the hypocretin neuropeptide effect, we investigate the limits of circuit activity regulation using a realistic model of neurons. Our investigation shows that GABAA inhibition is insufficient to control the activity levels of the LCs. Despite slower forms of GABAA can in principle work, there is not much plausibility due to the low probability of the presence of slow GABAA and lack of robust stability at the maximum firing frequencies. The best possible control mechanism predicted by our modeling analysis is the presence of inhibitory neuropeptides that exert effects in a similar time scale as the hypocretin/orexin. Although the nature of these inhibitory neuropeptides has not been identified yet, it provides the most efficient mechanism in the modeling analysis. Finally, we present a reduced mean-field model that perfectly captures the dynamics and the phenomena generated by this circuit. This investigation shows that brain communication involving multiple time scales can be better controlled by employing orthogonal mechanisms of neural transmission to decrease interference between cognitive processes and hypothalamic functions. PMID:25598695

  17. Molecular characterization of a short neuropeptide F signaling system in the tsetse fly, Glossina morsitans morsitans.

    PubMed

    Caers, Jelle; Peymen, Katleen; Van Hiel, Matthias B; Van Rompay, Liesbeth; Van Den Abbeele, Jan; Schoofs, Liliane; Beets, Isabel

    2016-09-01

    Neuropeptides of the short neuropeptide F (sNPF) family are widespread among arthropods and found in every sequenced insect genome so far. Functional studies have mainly focused on the regulatory role of sNPF in feeding behavior, although this neuropeptide family has pleiotropic effects including in the control of locomotion, osmotic homeostasis, sleep, learning and memory. Here, we set out to characterize and determine possible roles of sNPF signaling in the haematophagous tsetse fly Glossina morsitans morsitans, a vector of African Trypanosoma parasites causing human and animal African trypanosomiasis. We cloned the G. m. morsitans cDNA sequences of an sNPF-like receptor (Glomo-sNPFR) and precursor protein encoding four Glomo-sNPF neuropeptides. All four Glomo-sNPF peptides concentration-dependently activated Glomo-sNPFR in a cell-based calcium mobilization assay, with EC50 values in the nanomolar range. Gene expression profiles in adult female tsetse flies indicate that the Glomo-sNPF system is mainly restricted to the nervous system. Glomo-snpfr transcripts were also detected in the hindgut of adult females. In contrast to the Drosophila sNPF system, tsetse larvae lack expression of Glomo-snpf and Glomo-snpfr genes. While Glomo-snpf transcript levels are upregulated in pupae, the onset of Glomo-snpfr expression is delayed to adulthood. Expression profiles in adult tissues are similar to those in other insects suggesting that the tsetse sNPF system may have similar functions such as a regulatory role in feeding behavior, together with a possible involvement of sNPFR signaling in osmotic homeostasis. Our molecular data will enable further investigations into the functions of sNPF signaling in tsetse flies. PMID:27288635

  18. Interaction of mimetic analogs of insect kinin neuropeptides with arthropod receptors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insect kinin neuropeptides share a common C-terminal pentapeptide sequence Phe1-Xaa1-2-Xaa2-3-Trp4-Gly5-NH2 (Xaa1-2 = His, Asn, Phe, Ser or Tyr; Xaa2-3 = Pro, Ser or Ala) and have been isolated from a number of insects, including species of Dictyoptera, Lepidoptera, and Orthoptera. They have been a...

  19. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

    PubMed Central

    da Silva, M.P.; Cedraz-Mercez, P.L.; Varanda, W.A.

    2014-01-01

    Physiological evidence indicates that the supraoptic nucleus (SON) is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs) responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1) the intrinsic membrane properties of the MNCs themselves and 2) synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO) may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON. PMID:24519124

  20. Gender and pregnancy affect neuropeptide responses of the rabbit Achilles tendon.

    PubMed

    Hart, D A; Kydd, A; Reno, C

    1999-08-01

    Tendons such as the Achilles tendon are complex structures that are hypocellular, hypovascular, and hyponeural. The development of pathophysiologic function in this tendon because of overuse is relatively common; however, the mechanisms responsible for the development of paratenonitis and tendinosis remain primarily undefined. To understand better a possible regulatory role for neuropeptides (substance P and calcitonin gene related peptide) known to be present in this tissue, the influence of substance P and calcitonin gene related peptide on messenger ribonucleic acid levels for numerous inflammatory molecules, growth factors, and proteinases and inhibitors have been assessed using a semiquantitative reverse transcription-polymerase chain reaction method and explants of paratenon and Achilles tendon midsubstance tissue from adolescent male and female rabbits and tissue from primigravida females. Most of the significant (p < 0.01) changes observed were at the level of the growth factor transcripts and transcripts for proteinases and inhibitors. Twenty-one significant differences in the responsiveness between tissues from male and female rabbits were observed, and 12 significant differences in responsiveness between virgin females and primigravida rabbits were seen. Differences between paratenon and midsubstance responsiveness to the neuropeptides also were observed within each group of animals. The midsubstance tissue from pregnant animals was hyporesponsive to both neuropeptides. These results indicate that neurotransmitter responsiveness of Achilles tendon tissue differs in a gender specific manner and is influenced by pregnancy associated factors. PMID:10627708

  1. Radiosynthesis and in Vivo Evaluation of Neuropeptide Y5 Receptor (NPY5R) PET Tracers.

    PubMed

    Kumar, J S Dileep; Walker, Mary; Packiarajan, Mathivanan; Jubian, Vrej; Prabhakaran, Jaya; Chandrasena, Gamini; Pratap, Mali; Parsey, Ramin V; Mann, J John

    2016-05-18

    Neuropeptide Y receptor type 5 (NPY5R) is a G-protein coupled receptor (GPCR) that belongs to the subfamily of neuropeptide receptors (NPYR) that mediate the action of endogenous neuropeptide Y (NPY). Animal models and preclinical studies indicate a role for NPY5R in the pathophysiology of depression, anxiety, and obesity and as a target of potential therapeutic drugs. To better understand the pathophysiological involvement of NPY5R, and to measure target occupancy by potential therapeutic drugs, it would be advantageous to measure NPY5R binding in vivo by positron emission tomography (PET). Four potent and selective NPY5R antagonists were radiolabeled via nucleophilic aromatic substitution reactions with [(18)F]fluoride. Of the four radioligands investigated, PET studies in anesthetized baboons showed that [(18)F]LuAE00654 ([(18)F]N-[trans-4-({[4-(2-fluoropyridin-3-yl)thiazol-2-yl]amino}methyl)cyclohexyl]propane-2-sulfonamide) penetrates blood brain barrier (BBB) and a small amount is retained in the brain. Slow metabolism of [(18)F]LuAE00654 was observed in baboon plasma. Blocking studies with a specific NPY5R antagonist demonstrated up to 60% displacement of radioactivity in striatum, the brain region with highest NPY5R binding. Our studies suggest that [(18)F]LuAE00654 can be a potential PET radiotracer for the quantification and occupancy studies of NPY5R drug candidates. PMID:26886507

  2. Oxygen Sensing Neurons and Neuropeptides Regulate Survival after Anoxia in Developing C. elegans

    PubMed Central

    Flibotte, John J.; Jablonski, Angela M.; Kalb, Robert G.

    2014-01-01

    Hypoxic brain injury remains a major source of neurodevelopmental impairment for both term and preterm infants. The perinatal period is a time of rapid transition in oxygen environments and developmental resetting of oxygen sensing. The relationship between neural oxygen sensing ability and hypoxic injury has not been studied. The oxygen sensing circuitry in the model organism C. elegans is well understood. We leveraged this information to investigate the effects of impairments in oxygen sensing on survival after anoxia. There was a significant survival advantage in developing worms specifically unable to sense oxygen shifts below their preferred physiologic range via genetic ablation of BAG neurons, which appear important for conferring sensitivity to anoxia. Oxygen sensing that is mediated through guanylate cyclases (gcy-31, 33, 35) is unlikely to be involved in conferring this sensitivity. Additionally, animals unable to process or elaborate neuropeptides displayed a survival advantage after anoxia. Based on these data, we hypothesized that elaboration of neuropeptides by BAG neurons sensitized animals to anoxia, but further experiments indicate that this is unlikely to be true. Instead, it seems that neuropeptides and signaling from oxygen sensing neurons operate through independent mechanisms, each conferring sensitivity to anoxia in wild type animals. PMID:24967811

  3. Transcriptional regulation of neuropeptide and peptide hormone expression by the Drosophila dimmed and cryptocephal genes.

    PubMed

    Gauthier, Sebastien A; Hewes, Randall S

    2006-05-01

    The regulation of neuropeptide and peptide hormone gene expression is essential for the development and function of neuroendocrine cells in integrated physiological networks. In insects, a decline in circulating ecdysteroids triggers the activation of a neuroendocrine system to stimulate ecdysis, the behaviors used to shed the old cuticle at the culmination of each molt. Here we show that two evolutionarily conserved transcription factor genes, the basic helix-loop-helix (bHLH) gene dimmed (dimm) and the basic-leucine zipper (bZIP) gene cryptocephal (crc), control expression of diverse neuropeptides and peptide hormones in Drosophila. Central nervous system expression of three neuropeptide genes, Dromyosuppressin, FMRFamide-related and Leucokinin, is activated by dimm. Expression of Ecdysis triggering hormone (ETH) in the endocrine Inka cells requires crc; homozygous crc mutant larvae display markedly reduced ETH levels and corresponding defects in ecdysis. crc activates ETH expression though a 382 bp enhancer, which completely recapitulates the ETH expression pattern. The enhancer contains two evolutionarily conserved regions, and both are imperfect matches to recognition elements for activating transcription factor-4 (ATF-4), the vertebrate ortholog of the CRC protein and an important intermediate in cellular responses to endoplasmic reticulum stress. These regions also contain a putative ecdysteroid response element and a predicted binding site for the products of the E74 ecdysone response gene. These results suggest that convergence between ATF-related signaling and an important intracellular steroid response pathway may contribute to the neuroendocrine regulation of insect molting. PMID:16651547

  4. Seminalplasmin: recent evolution of another member of the neuropeptide Y gene family.

    PubMed Central

    Herzog, H; Hort, Y; Schneider, R; Shine, J

    1995-01-01

    Seminalplasmin, the major basic protein of bull semen, an important regulator of calcium transport in bovine sperm and a positive modulator of the zona pellucida-induced acrosome reaction, is shown to be a recently created member of the neuropeptide Y gene family. Sequence analysis of the bovine peptide YY-pancreatic polypeptide gene cluster reveals an unexpected and extensive homology between seminalplasmin and the neuropeptide Y gene family, at the level of both gene structure and primary amino acid and nucleotide sequences. The extremely high degree of homology to the peptide YY gene, in both coding and especially noncoding regions, suggests that the seminalplasmin gene has arisen by a very recent gene duplication of the bovine peptide YY gene. Despite the more than 95% nucleotide sequence identity, a few specific mutations in the seminalplasmin gene have resulted in both the loss of the amino- and carboxyl-terminal cleavage sites characteristic of all other members of the neuropeptide Y family and the acquisition of a function apparently unrelated to the neurotransmitter/endocrine role of peptide YY. PMID:7831336

  5. Amyloid-β / Neuropeptide Interactions Assessed by Ion Mobility-Mass Spectrometry

    PubMed Central

    Soper, Molly T.; DeToma, Alaina S.; Hyung, Suk-Joon; Lim, Mi Hee; Ruotolo, Brandon T.

    2013-01-01

    Recently, small peptides have been shown to modulate aggregation and toxicity of the amyloid-β protein (Aβ). As such, these new scaffolds may help discover a new class of biotherapeutics useful in the treatment of Alzheimer's disease. Many of these inhibitory peptide sequences have been derived from natural sources or from Aβ itself (e.g., C-terminal Aβ fragments). In addition, much earlier work indicates that tachykinins, a broad class of neuropeptides, display neurotrophic properties, presumably through direct interactions with either Aβ or its receptors. Based on this work, we undertook a limited screen of neuropeptides using ion mobility-mass spectrometry to search for similar such peptides with direct Aβ binding properties. Our results reveal that the neuropeptides leucine enkephalin (LE) and galanin interact with both the monomeric and small oligomeric forms of Aβ1-40 to create a range of complexes having diverse stoichiometries, while some tachyknins (i.e., substance P) do not. LE interacts with Aβ more strongly than galanin, and we utilized ion mobility-mass spectrometry, molecular dynamics simulations, gel electrophoresis/Western blot, and transmission electron microscopy to study the influence of this peptide on the structure of Aβ monomer, small Aβ oligomers, as well as the eventual formation of Aβ fibrils. We find that LE binds selectively within a region of Aβ between its N-terminal tail and hydrophobic core. Furthermore, our data indicate that LE modulates fibril generation, producing shorter fibrillar aggregates when added in stoichiometric excess relative to Aβ. PMID:23612608

  6. Urbilaterian origin of paralogous GnRH and corazonin neuropeptide signalling pathways.

    PubMed

    Tian, Shi; Zandawala, Meet; Beets, Isabel; Baytemur, Esra; Slade, Susan E; Scrivens, James H; Elphick, Maurice R

    2016-01-01

    Gonadotropin-releasing hormone (GnRH) is a key regulator of reproductive maturation in humans and other vertebrates. Homologs of GnRH and its cognate receptor have been identified in invertebrates-for example, the adipokinetic hormone (AKH) and corazonin (CRZ) neuropeptide pathways in arthropods. However, the precise evolutionary relationships and origins of these signalling systems remain unknown. Here we have addressed this issue with the first identification of both GnRH-type and CRZ-type signalling systems in a deuterostome-the echinoderm (starfish) Asterias rubens. We have identified a GnRH-like neuropeptide (pQIHYKNPGWGPG-NH2) that specifically activates an A. rubens GnRH-type receptor and a novel neuropeptide (HNTFTMGGQNRWKAG-NH2) that specifically activates an A. rubens CRZ-type receptor. With the discovery of these ligand-receptor pairs, we demonstrate that the vertebrate/deuterostomian GnRH-type and the protostomian AKH systems are orthologous and the origin of a paralogous CRZ-type signalling system can be traced to the common ancestor of the Bilateria (Urbilateria). PMID:27350121

  7. Les neuropeptides gastro-intestinaux cibles des effets des rayonnements ionisants : altérations fonctionnelles

    NASA Astrophysics Data System (ADS)

    Linard, C.; Esposito, V.; Wysocki, J.; Griffiths, N. M.

    1998-04-01

    The symptoms associated with exposure to ionizing radiation are nausea, vomiting, diarrhoea. The response of the gut is complex involving modifications of motility and fluid and electrolyte transport. Gastrointestinal regulatory peptides have an important role in these functions. This study showed that radiation-induced tissue variations of neuropeptides have some repercussions on intestinal biological activity of these peptides soon after irradiation. In addition such modifications are also seen a few years after irradiation. Les symptômes associés à l'exposition aux rayonnements ionisants sont des nausées, vomissements et diarrhées. La réponse du système digestif est complexe, impliquant des modifications de la motilité et du transport d'eau et d'électrolytes. les neuropeptides gastro-intestinaux ont un rôle important dans ces fonctions. Cette étude montre que les variations tissulaires de ces neuropeptides induites par l'irradiation ont des répercussions sur l'activité biologique intestinale pour des temps précoces mais que ces perturbations sont encore visibles quelques années après l'irradiation.

  8. Calcium-dependent growth regulation of small cell lung cancer cells by neuropeptides.

    PubMed

    Gudermann, Thomas; Roelle, Susanne

    2006-12-01

    Approximately 15-25% of all primary cancers of the lung are classified histologically as small cell lung carcinoma (SCLC), a subtype characterized by rapid growth and a poor prognosis. Neuropeptide hormones like bombesin/gastrin-releasing peptide, bradykinin or galanin are the principal mitogenic stimuli of this tumour entity. The mitogenic signal is transmitted into the cell via heptahelical neuropeptide hormone receptors, which couple to the heterotrimeric G proteins of the Gq/11 familiy. Subsequent activation of phospholipase Cbeta (PLCbeta) entails the activation of protein kinase C and the elevation of the intracellular calcium concentration. There is mounting evidence to support the notion that calcium mobilization is the key event that initiates different mitogen-activated protein kinase cascades. Neuropeptide-dependent proliferation of SCLC cells relies on parallel activation of the Gq/11/PLCbeta/Ras/extracellular signal-regulated kinase and the c-jun N-terminal kinase pathways, while selective engagement of either signalling cascade alone results in growth arrest and differentiation or apoptotic cell death. Basic experimental research has the potential to identify and validate novel therapeutic targets located at critical points of convergence of different mitogenic signal transduction pathways. In the case of SCLC, targeting the distinct components of the Ca2+ influx pathway as well as critical Ca2+-dependent cellular effectors may be rewarding in this regard. PMID:17158754

  9. Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits

    PubMed Central

    Baribeau, Danielle A.; Anagnostou, Evdokia

    2015-01-01

    Oxytocin and vasopressin are pituitary neuropeptides that have been shown to affect social processes in mammals. There is growing interest in these molecules and their receptors as potential precipitants of, and/or treatments for, social deficits in neurodevelopmental disorders, including autism spectrum disorder. Numerous behavioral-genetic studies suggest that there is an association between these peptides and individual social abilities; however, an explanatory model that links hormonal activity at the receptor level to complex human behavior remains elusive. The following review summarizes the known associations between the oxytocin and vasopressin neuropeptide systems and social neurocircuits in the brain. Following a micro- to macro- level trajectory, current literature on the synthesis and secretion of these peptides, and the structure, function and distribution of their respective receptors is first surveyed. Next, current models regarding the mechanism of action of these peptides on microcircuitry and other neurotransmitter systems are discussed. Functional neuroimaging evidence on the acute effects of exogenous administration of these peptides on brain activity is then reviewed. Overall, a model in which the local neuromodulatory effects of pituitary neuropeptides on brainstem and basal forebrain regions strengthen signaling within social neurocircuits proves appealing. However, these findings are derived from animal models; more research is needed to clarify the relevance of these mechanisms to human behavior and treatment of social deficits in neuropsychiatric disorders. PMID:26441508

  10. Urbilaterian origin of paralogous GnRH and corazonin neuropeptide signalling pathways

    PubMed Central

    Tian, Shi; Zandawala, Meet; Beets, Isabel; Baytemur, Esra; Slade, Susan E.; Scrivens, James H.; Elphick, Maurice R.

    2016-01-01

    Gonadotropin-releasing hormone (GnRH) is a key regulator of reproductive maturation in humans and other vertebrates. Homologs of GnRH and its cognate receptor have been identified in invertebrates–for example, the adipokinetic hormone (AKH) and corazonin (CRZ) neuropeptide pathways in arthropods. However, the precise evolutionary relationships and origins of these signalling systems remain unknown. Here we have addressed this issue with the first identification of both GnRH-type and CRZ-type signalling systems in a deuterostome–the echinoderm (starfish) Asterias rubens. We have identified a GnRH-like neuropeptide (pQIHYKNPGWGPG-NH2) that specifically activates an A. rubens GnRH-type receptor and a novel neuropeptide (HNTFTMGGQNRWKAG-NH2) that specifically activates an A. rubens CRZ-type receptor. With the discovery of these ligand-receptor pairs, we demonstrate that the vertebrate/deuterostomian GnRH-type and the protostomian AKH systems are orthologous and the origin of a paralogous CRZ-type signalling system can be traced to the common ancestor of the Bilateria (Urbilateria). PMID:27350121

  11. The reverse role of the hypothalamic paraventricular (PVN) and arcuate (ARC) nuclei in the central serotonergic regulation of the liver cytochrome P450 isoform CYP2C11.

    PubMed

    Rysz, Marta; Bromek, Ewa; Haduch, Anna; Liskova, Barbora; Wójcikowski, Jacek; Daniel, Władysława A

    2016-07-15

    Our recent work showed that the brain serotonergic system negatively regulated liver cytochrome P450. The aim of our present research was to study the effect of damage to the serotonergic innervation of the paraventricular (PVN) or arcuate nuclei (ARC) of the hypothalamus on the neuroendocrine regulation of cytochrome P450 (CYP). Male rats received bilateral injections of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the PVN or ARC. One week after the injection brain neurotransmitters, serum hormones (growth hormone, testosterone, corticosterone, thyroid hormones), pituitary somatostatin and liver cytochrome P450 expression and activity were measured. Lesion of the serotonergic innervation of the PVN decreased serotonin level in the hypothalamic area containing the PVN, causing an increase in growth hormone and testosterone concentrations in the blood and, subsequently, an increase in the expression (mRNA and protein level) and activity of isoform CYP2C11 in the liver. In contrast, damage to the serotonergic innervation of the ARC, which caused a decrease in serotonin level in the hypothalamic area containing the ARC, reduced the concentration of growth hormone and the expression and activity of CYP2C11. In conclusion, the obtained results show a reverse effect of the serotonergic innervation of the hypothalamic paraventricular (a negative effect) and arcuate nuclei (a positive effect) on growth hormone secretion and growth hormone-dependent CYP2C11 expression. They also suggest that CYP2C11 expression may be changed by drugs acting via the serotonergic system, their effect depending on their mechanism of action, route of administration (intracerebral, peripheral) and distribution pattern within the hypothalamus. PMID:27137992

  12. Comet nucleus sample return mission

    NASA Technical Reports Server (NTRS)

    1983-01-01

    A comet nucleus sample return mission in terms of its relevant science objectives, candidate mission concepts, key design/technology requirements, and programmatic issues is discussed. The primary objective was to collect a sample of undisturbed comet material from beneath the surface of an active comet and to preserve its chemical and, if possible, its physical integrity and return it to Earth in a minimally altered state. The secondary objectives are to: (1) characterize the comet to a level consistent with a rendezvous mission; (2) monitor the comet dynamics through perihelion and aphelion with a long lived lander; and (3) determine the subsurface properties of the nucleus in an area local to the sampled core. A set of candidate comets is discussed. The hazards which the spacecraft would encounter in the vicinity of the comet are also discussed. The encounter strategy, the sampling hardware, the thermal control of the pristine comet material during the return to Earth, and the flight performance of various spacecraft systems and the cost estimates of such a mission are presented.

  13. Theoretical antideuteron-nucleus absorptive cross sections

    NASA Technical Reports Server (NTRS)

    Buck, W. W.; Norbury, J. W.; Townsend, L. W.; Wilson, J. W.

    1993-01-01

    Antideuteron-nucleus absorptive cross sections for intermediate to high energies are calculated using an ion-ion optical model. Good agreement with experiment (within 15 percent) is obtained in this same model for (bar p)-nucleus cross sections at laboratory energies up to 15 GeV. We describe a technique for estimating antinucleus-nucleus cross sections from NN data and suggest that further cosmic ray studies to search for antideuterons and other antinuclei be undertaken.

  14. Three different prohormones yield a variety of Hydra-RFamide (Arg-Phe-NH2) neuropeptides in Hydra magnipapillata.

    PubMed Central

    Darmer, D; Hauser, F; Nothacker, H P; Bosch, T C; Williamson, M; Grimmelikhuijzen, C J

    1998-01-01

    The freshwater polyp Hydra is the most frequently used model for the study of development in cnidarians. Recently we isolated four novel Arg-Phe-NH2 (RFamide) neuropeptides, the Hydra-RFamides I-IV, from Hydra magnipapillata. Here we describe the molecular cloning of three different preprohormones from H. magnipapillata, each of which gives rise to a variety of RFamide neuropeptides. Preprohormone A contains one copy of unprocessed Hydra-RFamide I (QWLGGRFG), II (QWFNGRFG), III/IV [(KP)HLRGRFG] and two putative neuropeptide sequences (QLMSGRFG and QLMRGRFG). Preprohormone B has the same general organization as preprohormone A, but instead of unprocessed Hydra-RFamide III/IV it contains a slightly different neuropeptide sequence [(KP)HYRGRFG]. Preprohormone C contains one copy of unprocessed Hydra-RFamide I and seven additional putative neuropeptide sequences (with the common N-terminal sequence QWF/LSGRFGL). The two Hydra-RFamide II copies (in preprohormones A and B) are preceded by Thr residues, and the single Hydra-RFamide III/IV copy (in preprohormone A) is preceded by an Asn residue, confirming that cnidarians use unconventional processing signals to generate neuropeptides from their precursor proteins. Southern blot analyses suggest that preprohormones A and B are each coded for by a single gene, whereas one or possibly two closely related genes code for preprohormone C. Northern blot analyses and in situ hybridizations show that the gene coding for preprohormone A is expressed in neurons of both the head and foot regions of Hydra, whereas the genes coding for preprohormones B and C are specifically expressed in neurons of different regions of the head. All of this shows that neuropeptide biosynthesis in the primitive metazoan Hydra is already rather complex. PMID:9601069

  15. Effects of Starvation on Brain Short Neuropeptide F-1, -2, and -3 Levels and Short Neuropeptide F Receptor Expression Levels of the Silkworm, Bombyx mori

    PubMed Central

    Nagata, Shinji; Matsumoto, Sumihiro; Nakane, Tomohiro; Ohara, Ayako; Morooka, Nobukatsu; Konuma, Takahiro; Nagai, Chiaki; Nagasawa, Hiromichi

    2012-01-01

    In our previous report, we demonstrated the possibility that various regulatory neuropeptides influence feeding behavior in the silkworm, Bombyx mori. Among these feeding-related neuropeptides, short neuropeptide F (sNPF) exhibited feeding-accelerating activity when injected into B. mori larvae. Like other insect sNPFs, the deduced amino acid sequence of the cDNA encoding the sNPF precursor appears to produce multiple sNPF and sNPF-related peptides in B. mori. The presence of three sNPFs, sNPF-1, sNPF-2, and sNPF-3, in the brain of B. mori larvae was confirmed by direct MALDI-TOF mass spectrometric profiling. In addition, all three sNPFs are present in other larval ganglia. The presence of sNPF mRNA in the central nervous system (CNS) was also confirmed by Reverse transcription-polymerase chain reaction. Semi-quantitative analyses of sNPFs in the larval brain using matrix-assisted laser desorption ionization time-of-flight mass spectrometry further revealed that brain sNPF levels decrease in response to starvation, and that they recover with the resumption of feeding. These data suggest that sNPFs were depleted by the starvation process. Furthermore, food deprivation decreased the transcriptional levels of the sNPF receptor (BNGR-A10) in the brain and CNS, suggesting that the sNPF system is dependent on the feeding state of the insect and that the sNPF system may be linked to locomotor activity associated with foraging behavior. Since the injection of sNPFs accelerated the onset of feeding in B. mori larvae, we concluded that sNPFs are strongly related to feeding behavior. In addition, semi-quantitative MS analyses revealed that allatostatin, which is present in the larval brain, is also reduced in response to starvation, whereas the peptide level of Bommyosuppressin was not affected by different feeding states. PMID:22649403

  16. Isolation and identification of the cDNA encoding the pheromone biosynthesis activating neuropeptide and additional neuropeptides in the oriental tobacco budworm, Helicoverpa assulta (Lepidoptera: Noctuidae).

    PubMed

    Choi, M Y; Tanaka, M; Kataoka, H; Boo, K S; Tatsuki, S

    1998-10-01

    The present study is concerned with cloning and characterizing Has-PBAN cDNA which is 756 nucleotides long, isolated from the brain and suboesophageal ganglion complex (Br-Sg) of Helicoverpa assulta adults. The 194-amino acid sequence deduced from this cDNA possessed the proteolytic endocleavage sites to generate multiple peptides. From the processing of the prepro-hormone, it can be predicted that the cDNA has a PBAN domain with 33 amino acids and four additional peptide domains: 24 amino acid-, 7 amino acid-, 18 amino acid- and 8 amino acid-long sequences, with FXPR (or K) L (X = G, T or S) amidated at their C-termini. The amino acid sequence of all five predicted peptides, including the PBAN, are identical to that of Helicoverpa zea (Raina, A.K., Jaffe, H., Kempe, T.G., Keim, P., Blacher, R.W., Fales, H.M., Riley, C.T., Klun, J.A., Ridgway, R.L., Hayes, D.K., 1989. Identification of a neuropeptide hormone that regulates sex pheromone production in female moths. Science 244, 796-798 and Ma, P.W.K., Knipple, D.C., Roelofs, W.L., 1994. Structural organization of the Helicoverpa zea gene encoding the precursor protein for pheromone biosynthesis-activating neuropeptide and other neuropeptides. Proc. Natl. Acad. Sci., U.S.A. 91, 506-510). A single mRNA species corresponding to the size of Has-PBAN cDNA was detected from the Br-Sg of 1-3-day old female and male adults, and their expression was also at a similar level. Pheromone production was induced upon injection of female or male Br-Sg extracts or synthetic PBAN into the haemocoel of decapitated 1-3-day old female adults during the photophase when they are not supposed to produce pheromone. From these results, H. assulta adult females seem to use their own PBAN for regulating sex pheromone biosynthesis. Functions of the four other peptides ending with FXPR (or K) L in the Has-PBAN cDNA and of the male PBAN remain to be elucidated. PMID:9807222

  17. Profiles of secreted neuropeptides and catecholamines illustrate similarities and differences in response to stimulation by distinct secretagogues.

    PubMed

    Podvin, Sonia; Bundey, Richard; Toneff, Thomas; Ziegler, Michael; Hook, Vivian

    2015-09-01

    The goal of this study was to define profiles of secreted neuropeptide and catecholamine neurotransmitters that undergo co-release from sympathoadrenal chromaffin cells upon stimulation by distinct secretagogues. Chromaffin cells of the adrenal medulla participate in the dynamic responses to stress, especially that of 'fight and flight', and, thus, analyses of the co-release of multiple neurotransmitters is necessary to gain knowledge of how the stress response regulates cell-cell communication among physiological systems. Results of this study demonstrated that six different secretagogues stimulated the co-release of the neuropeptides Met-enkephalin, galanin, NPY, and VIP with the catecholamines dopamine, norepinephrine, and epinephrine. Importantly, the quantitative profiles of the secreted neurotransmitters showed similarities and differences upon stimulation by the different secretagogues evaluated, composed of KCl depolarization, nicotine, carbachol, PACAP, bradykinin, and histamine. The rank-orders of the secreted profiles of the neurotransmitters were generally similar among these secretagogues, but differences in the secreted amounts of each neurotransmitter occurred with different secretagogues. Epinephrine among the catecholamines showed the highest level of secretion. (Met)enkephalin showed the largest levels of secretion compared to the other neuropeptides examined. Levels of secreted catecholamines were greater than that of the neuropeptides. These data support the hypothesis that profiles of secreted neuropeptide and catecholamine neurotransmitters show similarities and differences upon stimulation by distinct secretagogues. These results illustrate the co-release of concerted neurotransmitter profiles that participate in the stress response of the sympathoadrenal nervous system. PMID:26092702

  18. Actomyosin contractility rotates the cell nucleus

    PubMed Central

    Kumar, Abhishek; Maitra, Ananyo; Sumit, Madhuresh; Ramaswamy, Sriram; Shivashankar, G. V.

    2014-01-01

    The cell nucleus functions amidst active cytoskeletal filaments, but its response to their contractile stresses is largely unexplored. We study the dynamics of the nuclei of single fibroblasts, with cell migration suppressed by plating onto micro-fabricated patterns. We find the nucleus undergoes noisy but coherent rotational motion. We account for this observation through a hydrodynamic approach, treating the nucleus as a highly viscous inclusion residing in a less viscous fluid of orientable filaments endowed with active stresses. Lowering actin contractility selectively by introducing blebbistatin at low concentrations drastically reduced the speed and coherence of the angular motion of the nucleus. Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the nucleus, with profile and magnitude consistent with the results of our theoretical approach. Coherent intracellular flows and consequent nuclear rotation thus appear to be an intrinsic property of cells. PMID:24445418

  19. Neuropeptide-Driven Cross-Modal Plasticity following Sensory Loss in Caenorhabditis elegans

    PubMed Central

    Rabinowitch, Ithai; Laurent, Patrick; Zhao, Buyun; Walker, Denise; Beets, Isabel; Schoofs, Liliane; Bai, Jihong; Schafer, William R.; Treinin, Millet

    2016-01-01

    Sensory loss induces cross-modal plasticity, often resulting in altered performance in remaining sensory modalities. Whereas much is known about the macroscopic mechanisms underlying cross-modal plasticity, only scant information exists about its cellular and molecular underpinnings. We found that Caenorhabditis elegans nematodes deprived of a sense of body touch exhibit various changes in behavior, associated with other unimpaired senses. We focused on one such behavioral alteration, enhanced odor sensation, and sought to reveal the neuronal and molecular mechanisms that translate mechanosensory loss into improved olfactory acuity. To this end, we analyzed in mechanosensory mutants food-dependent locomotion patterns that are associated with olfactory responses and found changes that are consistent with enhanced olfaction. The altered locomotion could be reversed in adults by optogenetic stimulation of the touch receptor (mechanosensory) neurons. Furthermore, we revealed that the enhanced odor response is related to a strengthening of inhibitory AWC→AIY synaptic transmission in the olfactory circuit. Consistently, inserting in this circuit an engineered electrical synapse that diminishes AWC inhibition of AIY counteracted the locomotion changes in touch-deficient mutants. We found that this cross-modal signaling between the mechanosensory and olfactory circuits is mediated by neuropeptides, one of which we identified as FLP-20. Our results indicate that under normal function, ongoing touch receptor neuron activation evokes FLP-20 release, suppressing synaptic communication and thus dampening odor sensation. In contrast, in the absence of mechanosensory input, FLP-20 signaling is reduced, synaptic suppression is released, and this enables enhanced olfactory acuity; these changes are long lasting and do not represent ongoing modulation, as revealed by optogenetic experiments. Our work adds to a growing literature on the roles of neuropeptides in cross

  20. Regulation of Sleep by Neuropeptide Y-Like System in Drosophila melanogaster

    PubMed Central

    He, Chunxia; Yang, Yunyan; Zhang, Mingming; Price, Jeffrey L.; Zhao, Zhangwu

    2013-01-01

    Sleep is important for maintenance of normal physiology in animals. In mammals, neuropeptide Y (NPY), a homolog of Drosophila neuropeptide F (NPF), is involved in sleep regulation, with different effects in human and rat. However, the function of NPF on sleep in Drosophila melanogaster has not yet been described. In this study, we investigated the effects of NPF and its receptor-neuropeptide F receptor (NPFR1) on Drosophila sleep. Male flies over-expressing NPF or NPFR1 exhibited increased sleep during the nighttime. Further analysis demonstrated that sleep episode duration during nighttime was greatly increased and sleep latency was significantly reduced, indicating that NPF and NPFR1 promote sleep quality, and their action on sleep is not because of an impact of the NPF signal system on development. Moreover, the homeostatic regulation of flies after sleep deprivation was disrupted by altered NPF signaling, since sleep deprivation decreased transcription of NPF in control flies, and there were less sleep loss during sleep deprivation and less sleep gain after sleep deprivation in flies overexpressing NPF and NPFR1 than in control flies, suggesting that NPF system auto-regulation plays an important role in sleep homeostasis. However, these effects did not occur in females, suggesting a sex-dependent regulatory function in sleep for NPF and NPFR1. NPF in D1 brain neurons showed male-specific expression, providing the cellular locus for male-specific regulation of sleep by NPF and NPFR1. This study brings a new understanding into sleep studies of a sexually dimorphic regulatory mode in female and male flies. PMID:24040211

  1. Acrolein depletes the neuropeptides CGRP and substance P in sensory nerves in rat respiratory tract.

    PubMed Central

    Springall, D R; Edginton, J A; Price, P N; Swanston, D W; Noel, C; Bloom, S R; Polak, J M

    1990-01-01

    The mammalian respiratory tract is densely innervated by autonomic and sensory nerves around airways and blood vessels. Subsets of these nerves contain a number of putative neurotransmitter peptides, such as substance P and calcitonin gene-related peptide (CGRP) in sensory nerves and vasoactive intestinal polypeptide (VIP), possibly serving autonomic functions. CGRP is also found in endocrine cells in rat airway epithelium. These peptides are all pharmacologically potent effectors of bronchial and vascular smooth muscle and bronchial secretion. Their functions in vivo are less well established. We have therefore examined the effects of inhaled acrolein, a sensory irritant, on three pulmonary neuropeptides: CGRP, substance P, and VIP. Groups of rats (n = 3 each) were exposed for 10 min to acrolein in air (Ct = 510, 1858, and 5693 mg.min/m3) or to air alone. Fifteen minutes later they were killed (pentabarbitone IP) and their respiratory tracts were dissected and fixed in 0.4% p-benzoquinone solution. Cryostat sections were stained by indirect immunofluorescence for a general nerve marker (PGP 9.5) and neuropeptides. The acrolein-treated animals had a dose-related decrease in tracheal substance P- and CGRP-immunoreactive nerve fibers compared with controls. No change was seen in total nerve fiber distribution and number (PGP 9.5) or VIP immunoreactivity, nor in CGRP-immunoreactive epithelial endocrine cells. It is concluded that the rat tracheal peptidergic nerves are a sensitive indicator of inhaled irritant substances. Their reduced immunoreactivity may be because of a release of sensory neuropeptides that could play a role in the physiological response to irritant or toxic compounds. Images FIGURE 4. a FIGURE 4. b FIGURE 5. a FIGURE 5. b FIGURE 6. a FIGURE 6. b FIGURE 7. a FIGURE 7. b FIGURE 7. c FIGURE 8. a FIGURE 8. b PMID:1696540

  2. Smoking Habits and Neuropeptides: Adiponectin, Brain-derived Neurotrophic Factor, and Leptin Levels.

    PubMed

    Kim, Ki-Woong; Won, Yong Lim; Ko, Kyung Sun; Roh, Ji Won

    2014-06-01

    This study aimed to identify changes in the level of neuropeptides among current smokers, former smokers, and individuals who had never smoked, and how smoking habits affect obesity and metabolic syndrome (MetS). Neuropeptide levels, anthropometric parameters, and metabolic syndrome diagnostic indices were determined among male workers; 117 of these had never smoked, whereas 58 and 198 were former and current smokers, respectively. The total sample comprised 373 male workers. The results obtained from anthropometric measurements showed that current smokers attained significantly lower body weight, body mass index, waist circumference, and abdominal fat thickness values than former smokers and those who had never smoked. Current smokers' eating habits proved worse than those of non-smokers and individuals who had never smoked. The level of brain-derived neurotrophic factor (BDNF) in the neuropeptides in the case of former smokers was 23.6 ± 9.2 pg/ml, higher than that of current smokers (20.4 ± 6.1) and individuals who had never smoked (22.4 ± 5.8) (F = 6.520, p = 0.002). The level of adiponectin among former smokers was somewhat lower than that of current smokers, whereas leptin levels were higher among former smokers than current smokers; these results were not statistically significant. A relationship was found between adiponectin and triglyceride among non-smokers (odds ratio = 0.660, β value = -0.416, p < 0.01) and smokers (odds ratio = 0.827, β value = -0.190, p < 0.05). Further, waist circumference among non-smokers (odds ratio = 1.622, β value = 0.483, p < 0.001) and smokers (odds ratio = 1.895, β value = 0.639, p < 0.001) was associated with leptin. It was concluded that cigarette smoking leads to an imbalance of energy expenditure and appetite by changing the concentration of neuropeptides such as adiponectin, BDNF, leptin, and hsCRP, and influences food intake, body weight, the body mass index, blood pressure, and abdominal fat, which are risk

  3. Theoretical study of the neuromedin U-8 (NmU-8) neuropeptide from porcine spinal cord

    NASA Astrophysics Data System (ADS)

    Alieva, Irada N.; Isakova, Nigar A.; Gojayev, Niftali M.

    2004-09-01

    The spatial organization and conformational properties of the neuromedin U-8 (NmU-8) neuropeptide from porcine spinal cord have been established by the method of molecular mechanics. The conformational states corresponding to the local minimum of the whole molecule potential energy are obtained. The backbone structure comprises a type II β-turn formed by residues Arg 5-Pro 6-Arg 7-Asn 8. A large flexibility of the Tyr 1-Phe 2-Leu 3-Phe 4 amino acids sequence in contrast to other segment of the molecule was observed.

  4. Effect of manganese treatment on the levels of neurotransmitters, hormones, and neuropeptides: modulation by stress

    SciTech Connect

    Hong, J.S.; Jung, C.R.; Seth, P.K.; Mason, G.; Bondy, S.C.

    1984-08-01

    Six weeks of daily intraperitoneal injection with manganese chloride (15 mg/kg body wt) reduced the normal weight gain of male Fischer-344 rats. This treatment depressed plasma testosterone and corticosterone levels, but prolactin levels were unaffected. The only significant changes in the levels of a variety of neuropeptides assayed in several regions were increases in the levels of hypothalamic substance P and pituitary neurotensin. Striatal serotonin, dopamine, and their metabolites were unchanged in manganese-exposed rats relative to saline-injected controls. However, the stress of injection combined with the effect of manganese appeared to significantly increase concentrations of striatal monoamines relative to uninjected controls.

  5. Challenges for the in vivo quantification of brain neuropeptides using microdialysis sampling and LC-MS.

    PubMed

    Van Wanseele, Yannick; De Prins, An; De Bundel, Dimitri; Smolders, Ilse; Van Eeckhaut, Ann

    2016-09-01

    In recent years, neuropeptides and their receptors have received an increased interest in neuropharmacological research. Although these molecules are considered relatively small compared with proteins, their in vivo quantification using microdialysis is more challenging than for small molecules. Low microdialysis recoveries, aspecific adsorption and the presence of various multiply charged precursor ions during ESI-MS/MS detection hampers the in vivo quantification of these low abundant biomolecules. Every step in the workflow, from sampling until analysis, has to be optimized to enable the sensitive analysis of these compounds in microdialysates. PMID:27554986

  6. Spatial organization and conformational peculiarities of the callatostatin family of neuropeptides.

    PubMed

    Alieva, I N; Velieva, L I; Alie, D I; Godjaev, N M

    2002-08-01

    The structures and conformational peculiarities of five members of the callatostatin family of neuropeptides, i.e. Leu- and Met-callatostatins, ranging in size from 8 to 16 amino acid residues have been investigated by a theoretical conformational analysis method. A comparative analysis of the conformational flexibilities of Met-callatostatin with those of the hydroxylated analogues, [Hyp2]- and [Hyp3]-Met-callatostatin has been carried out. Helically packed C-terminal pentapeptide in the structure of all investigated Leu-callatostatins are shown to be possible. The reason for the great number low-energy conformers for the callatostatin N-terminus is discussed. PMID:12212802

  7. Functional analysis of four neuropeptides, EH, ETH, CCAP and bursicon and their receptors, in adult ecdysis behavior of the red flour beetle, Tribolium castaneum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ecdysis behavior or shedding of the old cuticle in arthropods is driven by complex interactions among multiple neuropeptide signaling systems. To understand the roles of neuropeptides and their receptors in the red flour beetle, Tribolium castaneum, we performed systemic RNA interference (RNAi) uti...

  8. The retrotrapezoid nucleus and breathing.

    PubMed

    Guyenet, Patrice G; Stornetta, Ruth L; Abbott, Stephen B G; Depuy, Seth D; Kanbar, Roy

    2012-01-01

    The retrotrapezoid nucleus (RTN) is located in the rostral medulla oblongata close to the ventral surface and consists of a bilateral cluster of glutamatergic neurons that are non-aminergic and express homeodomain transcription factor Phox2b throughout life. These neurons respond vigorously to increases in local pCO(2) via cell-autonomous and paracrine (glial) mechanisms and receive additional chemosensory information from the carotid bodies. RTN neurons exclusively innervate the regions of the brainstem that contain the respiratory pattern generator (RPG). Lesion or inhibition of RTN neurons largely attenuates the respiratory chemoreflex of adult rats whereas their activation increases respiratory rate, inspiratory amplitude and active expiration. Phox2b mutations that cause congenital central hypoventilation syndrome in humans prevent the development of RTN neurons in mice. Selective deletion of the RTN Phox2b-VGLUT2 neurons by genetic means in mice eliminates the respiratory chemoreflex in neonates.In short, RTN Phox2b-VGLUT2 neurons are a major nodal point of the CNS network that regulates pCO(2) via breathing and these cells are probable central chemoreceptors. PMID:23080151

  9. The multifunctional lateral geniculate nucleus.

    PubMed

    Weyand, Theodore G

    2016-02-01

    Providing the critical link between the retina and visual cortex, the well-studied lateral geniculate nucleus (LGN) has stood out as a structure in search of a function exceeding the mundane 'relay'. For many mammals, it is structurally impressive: Exquisite lamination, sophisticated microcircuits, and blending of multiple inputs suggest some fundamental transform. This impression is bolstered by the fact that numerically, the retina accounts for a small fraction of its input. Despite such promise, the extent to which an LGN neuron separates itself from its retinal brethren has proven difficult to appreciate. Here, I argue that whereas retinogeniculate coupling is strong, what occurs in the LGN is judicious pruning of a retinal drive by nonretinal inputs. These nonretinal inputs reshape a receptive field that under the right conditions departs significantly from its retinal drive, even if transiently. I first review design features of the LGN and follow with evidence for 10 putative functions. Only two of these tend to surface in textbooks: parsing retinal axons by eye and functional group and gating by state. Among the remaining putative functions, implementation of the principle of graceful degradation and temporal decorrelation are at least as interesting but much less promoted. The retina solves formidable problems imposed by physics to yield multiple efficient and sensitive representations of the world. The LGN applies context, increasing content, and gates several of these representations. Even if the basic concentric receptive field remains, information transmitted for each LGN spike relative to each retinal spike is measurably increased. PMID:26479339

  10. Music and the nucleus accumbens.

    PubMed

    Mavridis, Ioannis N

    2015-03-01

    Music is a universal feature of human societies over time, mainly because it allows expression and regulation of strong emotions, thus influencing moods and evoking pleasure. The nucleus accumbens (NA), the most important pleasure center of the human brain (dominates the reward system), is the 'king of neurosciences' and dopamine (DA) can be rightfully considered as its 'crown' due to the fundamental role that this neurotransmitter plays in the brain's reward system. Purpose of this article was to review the existing literature regarding the relation between music and the NA. Studies have shown that reward value for music can be coded by activity levels in the NA, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward. Listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the NA. The functional connectivity between brain regions mediating reward, autonomic and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. Musical stimuli can significantly increase extracellular DA levels in the NA. NA DA and serotonin were found significantly higher in animals exposed to music. Finally, passive listening to unfamiliar although liked music showed activations in the NA. PMID:25102783

  11. Nucleus accumbens stimulation in pathological obesity.

    PubMed

    Harat, Marek; Rudaś, Marcin; Zieliński, Piotr; Birska, Julita; Sokal, Paweł

    2016-01-01

    One of the potential treatment methods of obesity is deep brain stimulation (DBS) of nucleus accumbens. We describe the case of 19 years old woman with hypothalamic obesity. She weighted 151.4 kg before DBS and the non-surgical methods proved to be inefficient. She was treated with implantation of DBS electrode to nucleus accumbens bilaterally. Results were measured with body mass index and neuropsychological tests. Follow-up was 14 months. Fourteen months after surgery weight was 138 kg, BMI was 48.3. Neuropsychological test results were intact. The presented case supports the thesis of treatment of obesity with nucleus accumbens stimulation. PMID:27154450

  12. Electrically evoked neuropeptide release and neurogenic inflammation differ between rat and human skin.

    PubMed

    Sauerstein, K; Klede, M; Hilliges, M; Schmelz, M

    2000-12-15

    Protein extravasation and vasodilatation can be induced by neuropeptides released from nociceptive afferents (neurogenic inflammation). We measured electrically evoked neuropeptide release and concomitant protein extravasation in human and rat skin using intradermal microdialysis. Plasmapheresis capillaries were inserted intradermally at a length of 1.5 cm in the volar forearm of human subjects or abdominal skin of rats. Capillaries were perfused with Ringer solution at a flow rate of 2.5 or 1.6 microl min(-1). After a baseline period of 60 min capillaries were stimulated electrically (1 Hz, 80 mA, 0.5 ms or 4 Hz, 30 mA, 0.5 ms) for 30 min using a surface electrode directly above the capillaries and a stainless-steel wire inserted in the capillaries. Total protein concentration was assessed photometrically and calcitonin gene-related peptide (CGRP) and substance P (SP) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). In rat skin, electrical stimulation increased CGRP and total protein concentration in the dialysate. SP measurements showed a larger variance but only for the 1 Hz stimulation was the increased release significant. In human skin, electrical stimulation provoked a large flare reaction and at a frequency of 4 Hz both CGRP and SP concentrations increased significantly. In spite of the large flare reactions no protein extravasation was induced, which suggests major species differences. It will be of interest to investigate whether the lack of neurogenic protein extravasation is also valid under pathophysiological conditions. PMID:11118507

  13. Discovery of defense- and neuropeptides in social ants by genome-mining.

    PubMed

    Gruber, Christian W; Muttenthaler, Markus

    2012-01-01

    Natural peptides of great number and diversity occur in all organisms, but analyzing their peptidome is often difficult. With natural product drug discovery in mind, we devised a genome-mining approach to identify defense- and neuropeptides in the genomes of social ants from Atta cephalotes (leaf-cutter ant), Camponotus floridanus (carpenter ant) and Harpegnathos saltator (basal genus). Numerous peptide-encoding genes of defense peptides, in particular defensins, and neuropeptides or regulatory peptide hormones, such as allatostatins and tachykinins, were identified and analyzed. Most interestingly we annotated genes that encode oxytocin/vasopressin-related peptides (inotocins) and their putative receptors. This is the first piece of evidence for the existence of this nonapeptide hormone system in ants (Formicidae) and supports recent findings in Tribolium castaneum (red flour beetle) and Nasonia vitripennis (parasitoid wasp), and therefore its confinement to some basal holometabolous insects. By contrast, the absence of the inotocin hormone system in Apis mellifera (honeybee), another closely-related member of the eusocial Hymenoptera clade, establishes the basis for future studies on the molecular evolution and physiological function of oxytocin/vasopressin-related peptides (vasotocin nonapeptide family) and their receptors in social insects. Particularly the identification of ant inotocin and defensin peptide sequences will provide a basis for future pharmacological characterization in the quest for potent and selective lead compounds of therapeutic value. PMID:22448224

  14. Sensory Neuropeptides and Endogenous Opioids Expression in Human Dental Pulp with Asymptomatic Inflammation: In Vivo Study

    PubMed Central

    Chavarria-Bolaños, Daniel; Flores-Reyes, Hector; Lombana-Sanchez, Nelson; Cerda-Cristerna, Bernardino; Pozos-Guillen, Amaury

    2015-01-01

    Purpose. This study quantified the expression of substance P (SP), calcitonin gene-related peptide (CGRP), β-endorphins (β-End), and methionine-enkephalin (Met-Enk) in human dental pulp following orthodontic intrusion. Methods. Eight patients were selected according to preestablished inclusion criteria. From each patient, two premolars (indicated for extraction due to orthodontic reasons) were randomly assigned to two different groups: the asymptomatic inflammation group (EXPg), which would undergo controlled intrusive force for seven days, and the control group (CTRg), which was used to determine the basal levels of each substance. Once extracted, dental pulp tissue was prepared to determine the expression levels of both neuropeptides and endogenous opioids by radioimmunoassay (RIA). Results. All samples from the CTRg exhibited basal levels of both neuropeptides and endogenous opioids. By day seven, all patients were asymptomatic, even when all orthodontic-intrusive devices were still active. In the EXPg, the SP and CGRP exhibited statistically significant different levels. Although none of the endogenous opioids showed statistically significant differences, they all expressed increasing trends in the EXPg. Conclusions. SP and CGRP were identified in dental pulp after seven days of controlled orthodontic intrusion movement, even in the absence of pain. PMID:26538838

  15. Evidence for the involvement of opioid neuropeptides in the adherence and migration of immunocompetent invertebrate hemocytes.

    PubMed Central

    Stefano, G B; Leung, M K; Zhao, X H; Scharrer, B

    1989-01-01

    Evidence for the participation of opioid neuropeptides in immunoregulatory activities, especially cellular adherence and migration, has been obtained in representatives of two phyla of invertebrates, the mollusc Mytilus edulis and the insect Leucophaea maderae. The injection of a synthetic analog of [Met]enkephalin [( D-Ala2,Met5]enkephalinamide, DAMA; 10(-6) M) had a stimulatory, naloxone-reversible effect on the directed migration of immunocompetent hemocytes. Incubation of hemolymph in the presence of exogenous or endogenous opioid material significantly enhanced the adherence of hemocytes on albumin-coated slides as demonstrated by use of indirect Zeiss-Zonax reflectance computer analysis. Conversely, hemocyte adherence was markedly reduced by the addition of naloxone (10(-8) M) to the incubation medium, either alone or in combination with DAMA. The antagonistic effects of naloxone on the stimulatory activities of opioids indicate that, like those previously reported in mammals, they are receptor-mediated. The presence of an endogenous [Met]enkephalin-like material was demonstrated in cell-free hemolymph as well as sequestered hemocytes by use of high-pressure liquid chromatography and radioimmunoassay. These results demonstrate that the capacity of immunocytes to release and respond to opioid neuropeptide messengers is not restricted to mammalian organisms but was developed early in the course of evolution. Images PMID:2536172

  16. Discovery by proteogenomics and characterization of an RF-amide neuropeptide from cone snail venom

    PubMed Central

    Robinson, Samuel D.; Safavi-Hemami, Helena; Raghuraman, Shrinivasan; Imperial, Julita S.; Papenfuss, Anthony T.; Teichert, Russell W.; Purcell, Anthony W.; Olivera, Baldomero M.; Norton, Raymond S.

    2015-01-01

    In this study, a proteogenomic annotation strategy was used to identify a novel bioactive peptide from the venom of the predatory marine snail Conus victoriae. The peptide, conorfamide-Vc1 (CNF-Vc1), defines a new gene family. The encoded mature peptide was unusual for conotoxins in that it was cysteine-free and, despite low overall sequence similarity, contained two short motifs common to known neuropeptides/hormones. One of these was the C-terminal RF-amide motif, commonly observed in neuropeptides from a range of organisms, including humans. The mature venom peptide was synthesized and characterized structurally and functionally. The peptide was bioactive upon injection into mice, and calcium imaging of mouse dorsal root ganglion (DRG) cells revealed that the peptide elicits an increase in intracellular calcium levels in a subset of DRG neurons. Unusually for most Conus venom peptides, it also elicited an increase in intracellular calcium levels in a subset of non-neuronal cells. PMID:25464369

  17. Electrically evoked neuropeptide release and neurogenic inflammation differ between rat and human skin

    PubMed Central

    Sauerstein, Katja; Klede, Monika; Hilliges, Marita; Schmelz, Martin

    2000-01-01

    Protein extravasation and vasodilatation can be induced by neuropeptides released from nociceptive afferents (neurogenic inflammation). We measured electrically evoked neuropeptide release and concomitant protein extravasation in human and rat skin using intradermal microdialysis. Plasmapheresis capillaries were inserted intradermally at a length of 1.5 cm in the volar forearm of human subjects or abdominal skin of rats. Capillaries were perfused with Ringer solution at a flow rate of 2.5 or 1.6 μl min−1. After a baseline period of 60 min capillaries were stimulated electrically (1 Hz, 80 mA, 0.5 ms or 4 Hz, 30 mA, 0.5 ms) for 30 min using a surface electrode directly above the capillaries and a stainless-steel wire inserted in the capillaries. Total protein concentration was assessed photometrically and calcitonin gene-related peptide (CGRP) and substance P (SP) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). In rat skin, electrical stimulation increased CGRP and total protein concentration in the dialysate. SP measurements showed a larger variance but only for the 1 Hz stimulation was the increased release significant. In human skin, electrical stimulation provoked a large flare reaction and at a frequency of 4 Hz both CGRP and SP concentrations increased significantly. In spite of the large flare reactions no protein extravasation was induced, which suggests major species differences. It will be of interest to investigate whether the lack of neurogenic protein extravasation is also valid under pathophysiological conditions. PMID:11118507

  18. Neurotransmitters and Neuropeptides: New Players in the Control of Islet of Langerhans' Cell Mass and Function.

    PubMed

    Di Cairano, Eliana S; Moretti, Stefania; Marciani, Paola; Sacchi, Vellea Franca; Castagna, Michela; Davalli, Alberto; Folli, Franco; Perego, Carla

    2016-04-01

    Islets of Langerhans control whole body glucose homeostasis, as they respond, releasing hormones, to changes in nutrient concentrations in the blood stream. The regulation of hormone secretion has been the focus of attention for a long time because it is related to many metabolic disorders, including diabetes mellitus. Endocrine cells of the islet use a sophisticate system of endocrine, paracrine and autocrine signals to synchronize their activities. These signals provide a fast and accurate control not only for hormone release but also for cell differentiation and survival, key aspects in islet physiology and pathology. Among the different categories of paracrine/autocrine signals, this review highlights the role of neurotransmitters and neuropeptides. In a manner similar to neurons, endocrine cells synthesize, accumulate, release neurotransmitters in the islet milieu, and possess receptors able to decode these signals. In this review, we provide a comprehensive description of neurotransmitter/neuropetide signaling pathways present within the islet. Then, we focus on evidence supporting the concept that neurotransmitters/neuropeptides and their receptors are interesting new targets to preserve β-cell function and mass. A greater understanding of how this network of signals works in physiological and pathological conditions would advance our knowledge of islet biology and physiology and uncover potentially new areas of pharmacological intervention. J. Cell. Physiol. 231: 756-767, 2016. © 2015 Wiley Periodicals, Inc. PMID:26332080

  19. Characterization, tissue distribution, and expression of neuropeptide Y in olive flounder Paralichthys olivaceus

    NASA Astrophysics Data System (ADS)

    Wang, Qian; Tan, Xungang; Du, Shaojun; Sun, Wei; You, Feng; Zhang, Peijun

    2015-05-01

    Neuropeptide Y (NPY) is a 36-amino acid peptide of the neuropeptide Y family that plays key roles in the regulation of food intake. In this study, we focused on NPY mRNA expression changes around feeding time and during food deprivation in olive flounder. The olive flounder NPY mRNA levels were analyzed in different tissues and a high level of expression was detected in the brain. We also demonstrated a correlation between NPY expression levels in the brain and feeding schedule. NPY expression levels in olive flounder maintained on a daily scheduled feeding regimen increased shortly before feeding and decreased after the scheduled feeding time. Compared with the -1 h group before feeding, NPY expression in the 3 h group after feeding decreased significantly ( P<0.05). Food deprivation led to an 81.7% decrease in NPY mRNA levels in the 24 h fasted group ( P<0.05) and a 91.7% decrease in the 48 h fasted group ( P<0.05). Therefore, our study demonstrates that NPY expression is associated with food intake in olive flounder. This result reveals the function of NPY in regulating food intake and its potential importance in olive flounder aquaculture.

  20. Discovery of Defense- and Neuropeptides in Social Ants by Genome-Mining

    PubMed Central

    Gruber, Christian W.; Muttenthaler, Markus

    2012-01-01

    Natural peptides of great number and diversity occur in all organisms, but analyzing their peptidome is often difficult. With natural product drug discovery in mind, we devised a genome-mining approach to identify defense- and neuropeptides in the genomes of social ants from Atta cephalotes (leaf-cutter ant), Camponotus floridanus (carpenter ant) and Harpegnathos saltator (basal genus). Numerous peptide-encoding genes of defense peptides, in particular defensins, and neuropeptides or regulatory peptide hormones, such as allatostatins and tachykinins, were identified and analyzed. Most interestingly we annotated genes that encode oxytocin/vasopressin-related peptides (inotocins) and their putative receptors. This is the first piece of evidence for the existence of this nonapeptide hormone system in ants (Formicidae) and supports recent findings in Tribolium castaneum (red flour beetle) and Nasonia vitripennis (parasitoid wasp), and therefore its confinement to some basal holometabolous insects. By contrast, the absence of the inotocin hormone system in Apis mellifera (honeybee), another closely-related member of the eusocial Hymenoptera clade, establishes the basis for future studies on the molecular evolution and physiological function of oxytocin/vasopressin-related peptides (vasotocin nonapeptide family) and their receptors in social insects. Particularly the identification of ant inotocin and defensin peptide sequences will provide a basis for future pharmacological characterization in the quest for potent and selective lead compounds of therapeutic value. PMID:22448224

  1. Tailless and Atrophin control Drosophila aggression by regulating neuropeptide signalling in the pars intercerebralis

    NASA Astrophysics Data System (ADS)

    Davis, Shaun M.; Thomas, Amanda L.; Nomie, Krystle J.; Huang, Longwen; Dierick, Herman A.

    2014-02-01

    Aggressive behaviour is widespread throughout the animal kingdom. However, its mechanisms are poorly understood, and the degree of molecular conservation between distantly related species is unknown. Here we show that knockdown of tailless (tll) increases aggression in Drosophila, similar to the effect of its mouse orthologue Nr2e1. Tll localizes to the adult pars intercerebralis (PI), which shows similarity to the mammalian hypothalamus. Knockdown of tll in the PI is sufficient to increase aggression and is rescued by co-expressing human NR2E1. Knockdown of Atrophin, a Tll co-repressor, also increases aggression, and both proteins physically interact in the PI. tll knockdown-induced aggression is fully suppressed by blocking neuropeptide processing or release from the PI. In addition, genetically activating PI neurons increases aggression, mimicking the aggression-inducing effect of hypothalamic stimulation. Together, our results suggest that a transcriptional control module regulates neuropeptide signalling from the neurosecretory cells of the brain to control aggressive behaviour.

  2. Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis.

    PubMed

    Prévost, Gaëtan; Jeandel, Lydie; Arabo, Arnaud; Coëffier, Moïse; El Ouahli, Mariama; Picot, Marie; Alexandre, David; Gobet, Françoise; Leprince, Jérôme; Berrahmoune, Hind; Déchelotte, Pierre; Malagon, Maria; Bonner, Caroline; Kerr-Conte, Julie; Chigr, Fatiha; Lefebvre, Hervé; Anouar, Youssef; Chartrel, Nicolas

    2015-08-01

    26RFa is a hypothalamic neuropeptide that promotes food intake. 26RFa is upregulated in obese animal models, and its orexigenic activity is accentuated in rodents fed a high-fat diet, suggesting that this neuropeptide might play a role in the development and maintenance of the obese status. As obesity is frequently associated with type 2 diabetes, we investigated whether 26RFa may be involved in the regulation of glucose homeostasis. In the current study, we show a moderate positive correlation between plasma 26RFa levels and plasma insulin in patients with diabetes. Plasma 26RFa concentration also increases in response to an oral glucose tolerance test. In addition, we found that 26RFa and its receptor GPR103 are present in human pancreatic β-cells as well as in the gut. In mice, 26RFa attenuates the hyperglycemia induced by a glucose load, potentiates insulin sensitivity, and increases plasma insulin concentrations. Consistent with these data, 26RFa stimulates insulin production by MIN6 insulinoma cells. Finally, we show, using in vivo and in vitro approaches, that a glucose load induces a massive secretion of 26RFa by the small intestine. Altogether, the present data indicate that 26RFa acts as an incretin to regulate glucose homeostasis. PMID:25858563

  3. Effects of risperidone treatment on the expression of hypothalamic neuropeptide in appetite regulation in Wistar rats.

    PubMed

    Kursungoz, Canan; Ak, Mehmet; Yanik, Tulin

    2015-01-30

    Although the use of atypical antipsychotic drugs has been successful in the treatment of schizophrenia, they can cause some complications in the long-term use, including weight gain. Patients using these drugs tend to disrupt treatment primarily due to side effects. The atypical antipsychotic mechanism of action regulates a number of highly disrupted neurotransmitter pathways in the brains of psychotic patients but may also cause impairment of neurohormonal pathways in different brain areas. In this study, we investigated the circulating levels of hypothalamic neurohormones, which are related to appetite regulation; neuropeptide Y (NPY); alpha melanocyte stimulating hormone (α-MSH); cocaine and amphetamine regulated transcript (CART); agouti-related peptide (AgRP); and leptin in male Wistar rats, which were treated with risperidone, a serotonin antagonist, for four weeks. Alterations in the mRNA expression levels of these candidate genes in the hypothalamus were also analyzed. We hypothesized that risperidone treatment might alter both hypothalamic and circulating levels of neuropeptides through serotonergic antagonism, resulting in weight gain. Gene expression studies revealed that the mRNA expression levels of proopiomelanocortin (POMC), AgRP, and NPY decreased as well as their plasma levels, except for NPY. Unexpectedly, CART mRNA levels increased when their plasma levels decreased. Because POMC neurons express the serotonin receptor (5HT2C), the serotonergic antagonism of risperidone on POMC neurons may cause an increase in appetite and thus increase food consumption even in a short-term trial in rats. PMID:25449893

  4. Neuropeptide F neurons modulate sugar reward during associative olfactory learning of Drosophila larvae.

    PubMed

    Rohwedder, Astrid; Selcho, Mareike; Chassot, Bérénice; Thum, Andreas S

    2015-12-15

    All organisms continuously have to adapt their behavior according to changes in the environment in order to survive. Experience-driven changes in behavior are usually mediated and maintained by modifications in signaling within defined brain circuits. Given the simplicity of the larval brain of Drosophila and its experimental accessibility on the genetic and behavioral level, we analyzed if Drosophila neuropeptide F (dNPF) neurons are involved in classical olfactory conditioning. dNPF is an ortholog of the mammalian neuropeptide Y, a highly conserved neuromodulator that stimulates food-seeking behavior. We provide a comprehensive anatomical analysis of the dNPF neurons on the single-cell level. We demonstrate that artificial activation of dNPF neurons inhibits appetitive olfactory learning by modulating the sugar reward signal during acquisition. No effect is detectable for the retrieval of an established appetitive olfactory memory. The modulatory effect is based on the joint action of three distinct cell types that, if tested on the single-cell level, inhibit and invert the conditioned behavior. Taken together, our work describes anatomically and functionally a new part of the sugar reinforcement signaling pathway for classical olfactory conditioning in Drosophila larvae. PMID:26234537

  5. Beta-amyloid peptides undergo regulated co-secretion with neuropeptide and catecholamine neurotransmitters.

    PubMed

    Toneff, Thomas; Funkelstein, Lydiane; Mosier, Charles; Abagyan, Armen; Ziegler, Michael; Hook, Vivian

    2013-08-01

    Beta-amyloid (Aβ) peptides are secreted from neurons, resulting in extracellular accumulation of Aβ and neurodegeneration of Alzheimer's disease. Because neuronal secretion is fundamental for the release of neurotransmitters, this study assessed the hypothesis that Aβ undergoes co-release with neurotransmitters. Model neuronal-like chromaffin cells were investigated, and results illustrate regulated, co-secretion of Aβ(1-40) and Aβ(1-42) with peptide neurotransmitters (galanin, enkephalin, and NPY) and catecholamine neurotransmitters (dopamine, norepinephrine, and epinephrine). Regulated secretion from chromaffin cells was stimulated by KCl depolarization and nicotine. Forskolin, stimulating cAMP, also induced co-secretion of Aβ peptides with peptide and catecholamine neurotransmitters. These data suggested the co-localization of Aβ with neurotransmitters in dense core secretory vesicles (DCSV) that store and secrete such chemical messengers. Indeed, Aβ was demonstrated to be present in DCSV with neuropeptide and catecholamine transmitters. Furthermore, the DCSV organelle contains APP and its processing proteases, β- and γ-secretases, that are necessary for production of Aβ. Thus, Aβ can be generated in neurotransmitter-containing DCSV. Human IMR32 neuroblastoma cells also displayed regulated secretion of Aβ(1-40) and Aβ(1-42) with the galanin neurotransmitter. These findings illustrate that Aβ peptides are present in neurotransmitter-containing DCSV, and undergo co-secretion with neuropeptide and catecholamine neurotransmitters that regulate brain functions. PMID:23747840

  6. Neuropeptide co-expression in hypothalamic kisspeptin neurons of laboratory animals and the human

    PubMed Central

    Skrapits, Katalin; Borsay, Beáta Á.; Herczeg, László; Ciofi, Philippe; Liposits, Zsolt; Hrabovszky, Erik

    2015-01-01

    Hypothalamic peptidergic neurons using kisspeptin (KP) and its co-transmitters for communication are critically involved in the regulation of mammalian reproduction and puberty. This article provides an overview of neuropeptides present in KP neurons, with a focus on the human species. Immunohistochemical studies reveal that large subsets of human KP neurons synthesize neurokinin B, as also shown in laboratory animals. In contrast, dynorphin described in KP neurons of rodents and sheep is found rarely in KP cells of human males and postmenopausal females. Similarly, galanin is detectable in mouse, but not human, KP cells, whereas substance P, cocaine- and amphetamine-regulated transcript and proenkephalin-derived opioids are expressed in varying subsets of KP neurons in humans, but not reported in ARC of other species. Human KP neurons do not contain neurotensin, cholecystokinin, proopiomelanocortin-derivatives, agouti-related protein, neuropeptide Y, somatostatin or tyrosine hydroxylase (dopamine). These data identify the possible co-transmitters of human KP cells. Neurochemical properties distinct from those of laboratory species indicate that humans use considerably different neurotransmitter mechanisms to regulate fertility. PMID:25713511

  7. The role of neuropeptide Y in the pathophysiology of atherosclerotic cardiovascular disease.

    PubMed

    Zhu, Ping; Sun, Weiwei; Zhang, Chenliang; Song, Zhiyuan; Lin, Shu

    2016-10-01

    With average life expectancy rising greatly, the incidence rate of arteriosclerotic cardiovascular disease (ASCVD) has significantly increased. The heart disease has now become the number one killer that threatens the global population health, the second is stroke. It will be of great significance to investigate the underlying pathophysiological mechanisms of ASCVD in order to promote effective prevention and treatment. The neuropeptide Y (NPY) has now been discovered for more than thirty years and is widely distributed in the central nervous system (CNS) and peripheral tissues. By combining with certain receptors, NPY performs a variety of physiological functions, including the regulation of food intake, cardiovascular effects, development, hormonal secretion, sexual behavior, biological rhythms, temperature and emotion. In ASCVD, increased peripheral NPY was involved in the pathophysiological process of atherosclerosis through affecting the vascular endothelial dysfunction, the formation of foam cells, the proliferation of vascular smooth muscle cells, the local inflammatory response of plaques and the activation and aggregation of platelets. Via central and/or the peripheral nervous system, increased NPY was associated with dyslipidemia, hypertension, obesity, diabetes, impaired glucose tolerance, and smoking which are all risk factors for ASCVD. In this review, we summarize the role of neuropeptide Y in the development of atherosclerotic cardiovascular disease. PMID:27389447

  8. Intranasal Neuropeptide Administration To Target the Human Brain in Health and Disease.

    PubMed

    Spetter, Maartje S; Hallschmid, Manfred

    2015-08-01

    Central nervous system control of metabolic function relies on the input of endocrine messengers from the periphery, including the pancreatic hormone insulin and the adipokine leptin. This concept primarily derives from experiments in animals where substances can be directly applied to the brain. A feasible approach to study the impact of peptidergic messengers on brain function in humans is the intranasal (IN) route of administration, which bypasses the blood-brain barrier and delivers neuropeptides to the brain compartment, but induces considerably less, if any, peripheral uptake than other administration modes. Experimental IN insulin administration has been extensively used to delineate the role of brain insulin signaling in the control of energy homeostasis, but also cognitive function in healthy humans. Clinical pilot studies have found beneficial effects of IN insulin in patients with memory deficits, suggesting that the IN delivery of this and other peptides bears some promise for new, selectively brain-targeted pharmaceutical approaches in the treatment of metabolic and cognitive disorders. More recently, experiments relying on the IN delivery of the hypothalamic hormone oxytocin, which is primarily known for its involvement in psychosocial processes, have provided evidence that oxytocin influences metabolic control in humans. The IN administration of leptin has been successfully tested in animal models but remains to be investigated in the human setting. We briefly summarize the literature on the IN administration of insulin, leptin, and oxytocin, with a particular focus on metabolic effects, and address limitations and perspectives of IN neuropeptide administration. PMID:25880274

  9. Injury of the Arcuate Fasciculus in the Nondominant Hemisphere by Subfalcine Herniation in Patients with Intracerebral Hemorrhage : Two Case Reports and Literature Review

    PubMed Central

    Jang, Sung Ho; Kim, Seong Ho

    2016-01-01

    Using diffusion tensor tractography (DTT), we demonstrated injury of the arcuate fasciculus (AF) in the nondominant hemisphere in two patients who showed subfalcine herniation after intracerebral hemorrhage (ICH) in the dominant hemisphere. Two patients (patient 1 and patient 2) with ICH and six age-matched control patients who have ICH on the left corona radiata and basal ganglia without subfalcine herniation were recruited for this study. DTT was performed at one month after onset in patient 1 and patient 2. AFs of both hemispheres in both patients were disrupted between Wernicke's and Broca's areas. The fractional anisotropy value and tract numbers of the right AFs in both patients were found to be more than two standard deviations lower than those of control patients. In contrast, the apparent diffusion coefficient value was more than two standard deviations higher than those of control patients. Using the configuration and parameters of DTT, we confirmed injury of the AF in the nondominant hemisphere in two patients with subfalcine herniation following ICH in the dominant hemisphere. Therefore, DTT would be a useful tool for detection of underlying injury of the AF in the nondominant hemisphere in patients with subfalcine herniation. PMID:27226866

  10. Dynamic risk control by human nucleus accumbens.

    PubMed

    Nachev, Parashkev; Lopez-Sosa, Fernando; Gonzalez-Rosa, Javier Jesus; Galarza, Ana; Avecillas, Josue; Pineda-Pardo, Jose Angel; Lopez-Ibor, Juan José; Reneses, Blanca; Barcia, Juan Antonio; Strange, Bryan

    2015-12-01

    Real-world decisions about reward often involve a complex counterbalance of risk and value. Although the nucleus accumbens has been implicated in the underlying neural substrate, its criticality to human behaviour remains an open question, best addressed with interventional methodology that probes the behavioural consequences of focal neural modulation. Combining a psychometric index of risky decision-making with transient electrical modulation of the nucleus accumbens, here we reveal profound, highly dynamic alteration of the relation between probability of reward and choice during therapeutic deep brain stimulation in four patients with treatment-resistant psychiatric disease. Short-lived phasic electrical stimulation of the region of the nucleus accumbens dynamically altered risk behaviour, transiently shifting the psychometric function towards more risky decisions only for the duration of stimulation. A critical, on-line role of human nucleus accumbens in dynamic risk control is thereby established. PMID:26428667

  11. Testing string dynamics in lepton nucleus reactions

    SciTech Connect

    Gyulassy, M.; Pluemer, M.

    1989-10-01

    The sensitivity of nuclear attenuation of 10-100 GeV lepton nucleus ({ell}A) reactions to space-time aspects of hadronization is investigated within the context of the Lund string model. We consider two mechanisms for attenuation in a nucleus: final state cascading and string flip excitations. Implications for the evolution of the energy density in nuclear collisions are discussed. 16 refs., 10 figs.

  12. Volumes of cochlear nucleus regions in rodents.

    PubMed

    Godfrey, Donald A; Lee, Augustine C; Hamilton, Walter D; Benjamin, Louis C; Vishwanath, Shilpa; Simo, Hermann; Godfrey, Lynn M; Mustapha, Abdurrahman I A A; Heffner, Rickye S

    2016-09-01

    The cochlear nucleus receives all the coded information about sound from the cochlea and is the source of auditory information for the rest of the central auditory system. As such, it is a critical auditory nucleus. The sizes of the cochlear nucleus as a whole and its three major subdivisions - anteroventral cochlear nucleus (AVCN), posteroventral cochlear nucleus (PVCN), and dorsal cochlear nucleus (DCN) - have been measured in a large number of mammals, but measurements of its subregions at a more detailed level for a variety of species have not previously been made. Size measurements are reported here for the summed granular regions, DCN layers, AVCN, PVCN, and interstitial nucleus in 15 different rodent species, as well as a lagomorph, carnivore, and small primate. This further refinement of measurements is important because the granular regions and superficial layers of the DCN appear to have some different functions than the other cochlear nucleus regions. Except for DCN layers in the mountain beaver, all regions were clearly identifiable in all the animals studied. Relative regional size differences among most of the rodents, and even the 3 non-rodents, were not large and did not show a consistent relation to their wide range of lifestyles and hearing parameters. However, the mountain beaver, and to a lesser extent the pocket gopher, two rodents that live in tunnel systems, had relative sizes of summed granular regions and DCN molecular layer distinctly larger than those of the other mammals. Among all the mammals studied, there was a high correlation between the size per body weight of summed granular regions and that of the DCN molecular layer, consistent with other evidence for a close relationship between granule cells and superficial DCN neurons. PMID:27435005

  13. Commissural axons of the mouse cochlear nucleus.

    PubMed

    Brown, M Christian; Drottar, Marie; Benson, Thane E; Darrow, Keith

    2013-05-01

    The axons of commissural neurons that project from one cochlear nucleus to the other were studied after labeling with anterograde tracer. Injections were made into the dorsal subdivision of the cochlear nucleus in order to restrict labeling only to the group of commissural neurons that gave off collaterals to, or were located in, this subdivision. The number of labeled commissural axons in each injection was correlated with the number of labeled radiate multipolar neurons, suggesting radiate neurons as the predominant origin of the axons. The radiate commissural axons are thick and myelinated, and they exit the dorsal acoustic stria of the injected cochlear nucleus to cross the brainstem in the dorsal half, near the crossing position of the olivocochlear bundle. They enter the opposite cochlear nucleus via the dorsal and ventral acoustic stria and at its medial border. Reconstructions of single axons demonstrate that terminations are mostly in the core and typically within a single subdivision of the cochlear nucleus. Extents of termination range from narrow to broad along both the dorsoventral (i.e., tonotopic) and the rostrocaudal dimensions. In the electron microscope, labeled swellings form synapses that are symmetric (in that there is little postsynaptic density), a characteristic of inhibitory synapses. Our labeled axons do not appear to include excitatory commissural axons that end in edge regions of the nucleus. Radiate commissural axons could mediate the broadband inhibition observed in responses to contralateral sound, and they may balance input from the two ears with a quick time course. PMID:23124982

  14. Involvement of neuropeptide Y in the acute, chronic and withdrawal responses of morphine in nociception in neuropathic rats: behavioral and neuroanatomical correlates.

    PubMed

    Upadhya, Manoj A; Dandekar, Manoj P; Kokare, Dadasaheb M; Singru, Praful S; Subhedar, Nishikant K

    2009-08-01

    Although morphine is a potent antinociceptive agent, its chronic use developed tolerance in neuropathic pain (NP). Furthermore, opioid antagonist naloxone attenuated the antinociceptive effect of neuropeptide Y (NPY). The present study investigated the role of NPY and NPY Y1/Y5 receptors in acute and chronic actions of morphine in neuropathic rats using thermal paw withdrawal test and immunocytochemistry. In acute study, intracerebroventricular (icv) administration of morphine, NPY or NPY Y1/Y5 receptors agonist [Leu(31),Pro(34)]-NPY produced antinociception, whereas selective NPY Y1 receptors antagonist BIBP3226 caused hyperalgesia. While NPY or [Leu(31),Pro(34)]-NPY potentiated, BIBP3226 attenuated morphine induced antinociception. Chronic icv infusion of morphine via osmotic minipumps developed tolerance to its antinociceptive effect, and produced hyperalgesia following withdrawal. However, co-administration of NPY or [Leu(31),Pro(34)]-NPY prevented the development of tolerance and withdrawal hyperalgesia. Sciatic nerve ligation resulted in significant increase in the NPY-immunoreactive (NPY-ir) fibers in ventrolateral periaqueductal gray (VLPAG) and locus coeruleus (LC); fibers in the dorsal part of dorsal raphe nucleus (DRD) did not respond. While chronic morphine treatment significantly reduced NPY-ir fibers in VLPAG and DRD, morphine withdrawal triggered significant augmentation in NPY-immunoreactivity in the VLPAG. NPY-immunoreactivity profile of LC remained unchanged in all the morphine treatment conditions. Furthermore, removal of sciatic nerve ligation reversed the effects of NP, increased pain threshold and restored NPY-ir fiber population in VLPAG. NPY, perhaps acting via Y1/Y5 receptors, might profoundly influence the processing of NP information and interact with the endogenous opioid system primarily within the framework of the VLPAG. PMID:19556004

  15. Improved Cloud Condensation Nucleus Spectrometer

    NASA Technical Reports Server (NTRS)

    Leu, Ming-Taun

    2010-01-01

    An improved thermal-gradient cloud condensation nucleus spectrometer (CCNS) has been designed to provide several enhancements over prior thermal- gradient counters, including fast response and high-sensitivity detection covering a wide range of supersaturations. CCNSs are used in laboratory research on the relationships among aerosols, supersaturation of air, and the formation of clouds. The operational characteristics of prior counters are such that it takes long times to determine aerosol critical supersaturations. Hence, there is a need for a CCNS capable of rapid scanning through a wide range of supersaturations. The present improved CCNS satisfies this need. The improved thermal-gradient CCNS (see Figure 1) incorporates the following notable features: a) The main chamber is bounded on the top and bottom by parallel thick copper plates, which are joined by a thermally conductive vertical wall on one side and a thermally nonconductive wall on the opposite side. b) To establish a temperature gradient needed to establish a supersaturation gradient, water at two different regulated temperatures is pumped through tubes along the edges of the copper plates at the thermally-nonconductive-wall side. Figure 2 presents an example of temperature and supersaturation gradients for one combination of regulated temperatures at the thermally-nonconductive-wall edges of the copper plates. c) To enable measurement of the temperature gradient, ten thermocouples are cemented to the external surfaces of the copper plates (five on the top plate and five on the bottom plate), spaced at equal intervals along the width axis of the main chamber near the outlet end. d) Pieces of filter paper or cotton felt are cemented onto the interior surfaces of the copper plates and, prior to each experimental run, are saturated with water to establish a supersaturation field inside the main chamber. e) A flow of monodisperse aerosol and a dilution flow of humid air are introduced into the main

  16. The effect of intracerebroventricular infusions of leptin on the immunoreactivity of neuropeptide Y and gonadotrophin releasing hormone neurons in the hypothalamus of prepubertal sheep in conditions of short fasting.

    PubMed

    Polkowska, Jolanta; Wójcik-Gładysz, Anna; Wańkowska, Marta

    2006-08-01

    In the study we evaluated the effects of infusion of exogenous leptin to the third ventricle of the brain on the expression of immunoreactive (ir) neuropeptide Y (NPY) neurons in the hypothalamus and ir gonadotrophin releasing hormone (GnRH) nerve terminals in the median eminence of prepubertal lambs in the conditions of short fasting. Merino female sheep (n=16) were randomly divided into four groups, two fed with standard feeds and two fasted for 72 h. One standard and one fasted groups were infused with Ringer saline (controls), remaining standard and fasted groups with leptin (25 microg/120 microl/h), for 4 h during three consecutive days, and then slaughtered. Ir NPY and ir GnRH were localized by immunohistochemistry using specific polyclonal antibodies. Detection of both hormones was followed by the image analysis and expressed as the percent area stained and integral density of immunostaining. In the hypothalami from all groups the ir NPY perikarya and varicose nerve fibers were localized in three distinct sub-areas, in the arcuate (ARC), paraventricular and periventricular nuclei. In fasted sheep the percent area and integral density for immunoreactivity of NPY increased significantly (P<0.001) in three sub-areas compared to the standard-fed animals. Leptin infusion lowered the both parameters (P<0.001) but solely in the ARC NPY population of fasted sheep. The percent area and integral density of immunostaining for ir GnRH in fasted sheep revealed the augmentation (P<0.001) compared to standard-fed sheep. Leptin infusions diminished (P<0.001) both parameters in fasted, without effects in standard-fed lambs. In conclusion, the enhanced by fasting immunoreactivity of the ARC NPY perikarya and varicose nerve fibers and restrained immunoreaction of GnRH terminals in the median eminence were reversed by exogenous leptin. It is suggested that leptin can affect GnRH release via ARC NPY neurons in conditions of deficit of nutrients in prepubertal, female lambs. PMID

  17. Neuropeptide signaling sequences identified by pyrosequencing of the American dog tick synganglion transcriptome during blood feeding and reproduction.

    PubMed

    Donohue, Kevin V; Khalil, Sayed M S; Ross, E; Grozinger, Christina M; Sonenshine, Daniel E; Michael Roe, R

    2010-01-01

    Ticks are important vectors of numerous pathogens that impact human and animal health. The tick central nervous system represents an understudied area in tick biology and no tick synganglion-specific transcriptome has been described to date. Here we characterize whole or partial cDNA sequences of fourteen putative neuropeptides (allatostatin, insulin-like peptide, ion-transport peptide, sulfakinin, bursicon alpha/beta, eclosion hormone, glycoprotein hormone alpha/beta, corazonin, four orcokinins) and five neuropeptide receptors (gonadotropin receptor, leucokinin-like receptor, sulfakinin receptor, calcitonin receptor, pyrokinin receptor) translated from cDNA synthesized from the synganglion of unfed, partially fed and replete female American dog ticks, Dermacentor variabilis. Their homology to the same neuropeptides in other taxa is discussed. Many of these neuropeptides such as an allatostatin, insulin-like peptide, eclosion hormone, bursicon alpha and beta and glycoprotein hormone alpha and beta have not been previously described in the Chelicerata. An insulin-receptor substrate protein was also found indicating that an insulin signaling network is present in ticks. A putative type-2 proprotein processing convertase was also sequenced that may be involved in cleavage at monobasic and dibasic endoproteolytic cleavage sites in prohormones. The possible physiological role of the proteins discovered in adult tick blood feeding and reproduction will be discussed. PMID:20060044

  18. Gqalpha-linked PLCbeta and PLCgamma are essential components of the pheromone biosynthesis activating neuropeptide (PBAN) signal transduction cascade

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sex pheromone production for most moths is regulated by pheromone biosynthesis activating neuropeptide (PBAN). In Bombyx mori, PBAN binding triggers the opening of store-operated Ca2+ channels, suggesting the involvement of a receptor-activated phospholipase C (PLC). In this study, we found that P...

  19. Neuropeptide Y, its localization in the human cervix and possible effect on the contractile activity of cervix smooth muscle.

    PubMed

    Norström, A; Bryman, I; Dahlström, A

    1992-01-01

    Immunochemical methods were used to identify neuropeptide Y (NPY) in the cervical tissue of women at early and term pregnancy. NPY-containing fibers could not be demonstrated in the upper and lower uterine segments at term, but the cervical innervation persisted during labor. Moreover, NPY alone did not affect cervical contractile activity, although the stimulatory effect of noradrenaline was enhanced. PMID:1427420

  20. FRPR-4 Is a G-Protein Coupled Neuropeptide Receptor That Regulates Behavioral Quiescence and Posture in Caenorhabditis elegans

    PubMed Central

    York, Neil; Lee, Kun He; Schoofs, Liliane; Raizen, David M.

    2015-01-01

    Neuropeptides signal through G-protein coupled receptors (GPCRs) to regulate a broad array of animal behaviors and physiological processes. The Caenorhabditis elegans genome encodes approximately 100 predicted neuropeptide receptor GPCRs, but in vivo roles for only a few have been identified. We describe here a role for the GPCR FRPR-4 in the regulation of behavioral quiescence and locomotive posture. FRPR-4 is activated in cell culture by several neuropeptides with an amidated isoleucine-arginine-phenylalanine (IRF) motif or an amidated valine-arginine-phenylalanine (VRF) motif at their carboxy termini, including those encoded by the gene flp-13. Loss of frpr-4 function results in a minor feeding quiescence defect after heat-induced cellular stress. Overexpression of frpr-4 induces quiescence of locomotion and feeding as well as an exaggerated body bend posture. The exaggerated body bend posture requires the gene flp-13. While frpr-4 is expressed broadly, selective overexpression of frpr-4 in the proprioceptive DVA neurons results in exaggerated body bends that require flp-13 in the ALA neuron. Our results suggest that FLP-13 and other neuropeptides signal through FRPR-4 and other receptors to regulate locomotion posture and behavioral quiescence. PMID:26571132

  1. Marked changes in neuropeptide expression accompany broadcast spawnings in the gastropod Haliotis asinina

    PubMed Central

    2012-01-01

    Introduction A huge diversity of marine species reproduce by synchronously spawning their gametes into the water column. Although this species-specific event typically occurs in a particular season, the precise time and day of spawning often can not be predicted. There is little understanding of how the environment (e.g. water temperature, day length, tidal and lunar cycle) regulates a population’s reproductive physiology to synchronise a spawning event. The Indo-Pacific tropical abalone, Haliotis asinina, has a highly predictable spawning cycle, where individuals release gametes on the evenings of spring high tides on new and full moons during the warmer half of the year. These calculable spawning events uniquely allow for the analysis of the molecular and cellular processes underlying reproduction. Here we characterise neuropeptides produced in H. asinina ganglia that are known in egg-laying molluscs to control vital aspects of reproduction. Results We demonstrate that genes encoding APGWamide, myomodulin, the putative proctolin homologue whitnin, FMRFamide, a schistosomin-like peptide (SLP), a molluscan insulin-related peptide (MIP) and a haliotid growth-associated peptide (HGAP) all are differentially expressed in the anterior ganglia during the two week spawning cycle in both male and female abalone. Each gene has a unique and sex-specific expression profile. Despite these differences, expression levels in most of the genes peak at or within 12 h of the spawning event. In contrast, lowest levels of transcript abundance typically occurs 36 h before and 24 h after spawning, with differences in peak and low expression levels being most pronounced in genes orthologous to known molluscan reproduction neuromodulators. Conclusions Exploiting the predictable semi-lunar spawning cycle of the gastropod H. asinina, we have identified a suite of evolutionarily-conserved, mollusc-specific and rapidly-evolving neuropeptides that appear to contribute to the

  2. Oxytocin promotes functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioregulatory nuclei.

    PubMed

    Yee, Jason R; Kenkel, William M; Frijling, Jessie L; Dodhia, Sonam; Onishi, Kenneth G; Tovar, Santiago; Saber, Maha J; Lewis, Gregory F; Liu, Wensheng; Porges, Stephen W; Carter, C Sue

    2016-04-01

    The neuropeptide oxytocin (OXT) facilitates prosocial behavior and selective sociality. In the context of stress, OXT also can down-regulate hypothalamic-pituitary-adrenal (HPA) axis activity, leading to consideration of OXT as a potential treatment for many socioaffective disorders. However, the mechanisms through which administration of exogenous OXT modulates social behavior in stressful environmental contexts are not fully understood. Here, we investigate the hypothesis that autonomic pathways are components of the mechanisms through which OXT aids the recruitment of social resources in stressful contexts that may elicit mobilized behavioral responses. Female prairie voles (Microtus ochrogaster) underwent a stressor (walking in shallow water) following pretreatment with intraperitoneal OXT (0.25mg/kg) or OXT antagonist (OXT-A, 20mg/kg), and were allowed to recover with or without their sibling cagemate. Administration of OXT resulted in elevated OXT concentrations in plasma, but did not dampen the HPA axis response to a stressor. However, OXT, but not OXT-A, pretreatment prevented the functional coupling, usually seen in the absence of OXT, between paraventricular nucleus (PVN) activity as measured by c-Fos immunoreactivity and HPA output (i.e. corticosterone release). Furthermore, OXT pretreatment resulted in functional coupling between PVN activity and brain regions regulating both sympathetic (i.e. rostral ventrolateral medulla) and parasympathetic (i.e. dorsal vagal complex and nucleus ambiguous) branches of the autonomic nervous system. These findings suggest that OXT increases central neural control of autonomic activity, rather than strictly dampening HPA axis activity, and provides a potential mechanism through which OXT may facilitate adaptive and context-dependent behavioral and physiological responses to stressors. PMID:26836772

  3. Persistent neuronal Ube3a expression in the suprachiasmatic nucleus of Angelman syndrome model mice.

    PubMed

    Jones, Kelly A; Han, Ji Eun; DeBruyne, Jason P; Philpot, Benjamin D

    2016-01-01

    Mutations or deletions of the maternal allele of the UBE3A gene cause Angelman syndrome (AS), a severe neurodevelopmental disorder. The paternal UBE3A/Ube3a allele becomes epigenetically silenced in most neurons during postnatal development in humans and mice; hence, loss of the maternal allele largely eliminates neuronal expression of UBE3A protein. However, recent studies suggest that paternal Ube3a may escape silencing in certain neuron populations, allowing for persistent expression of paternal UBE3A protein. Here we extend evidence in AS model mice (Ube3a(m-/p+)) of paternal UBE3A expression within the suprachiasmatic nucleus (SCN), the master circadian pacemaker. Paternal UBE3A-positive cells in the SCN show partial colocalization with the neuropeptide arginine vasopressin (AVP) and clock proteins (PER2 and BMAL1), supporting that paternal UBE3A expression in the SCN is often of neuronal origin. Paternal UBE3A also partially colocalizes with a marker of neural progenitors, SOX2, implying that relaxed or incomplete imprinting of paternal Ube3a reflects an overall immature molecular phenotype. Our findings highlight the complexity of Ube3a imprinting in the brain and illuminate a subpopulation of SCN neurons as a focal point for future studies aimed at understanding the mechanisms of Ube3a imprinting. PMID:27306933

  4. Persistent neuronal Ube3a expression in the suprachiasmatic nucleus of Angelman syndrome model mice

    PubMed Central

    Jones, Kelly A.; Han, Ji Eun; DeBruyne, Jason P.; Philpot, Benjamin D.

    2016-01-01

    Mutations or deletions of the maternal allele of the UBE3A gene cause Angelman syndrome (AS), a severe neurodevelopmental disorder. The paternal UBE3A/Ube3a allele becomes epigenetically silenced in most neurons during postnatal development in humans and mice; hence, loss of the maternal allele largely eliminates neuronal expression of UBE3A protein. However, recent studies suggest that paternal Ube3a may escape silencing in certain neuron populations, allowing for persistent expression of paternal UBE3A protein. Here we extend evidence in AS model mice (Ube3am–/p+) of paternal UBE3A expression within the suprachiasmatic nucleus (SCN), the master circadian pacemaker. Paternal UBE3A-positive cells in the SCN show partial colocalization with the neuropeptide arginine vasopressin (AVP) and clock proteins (PER2 and BMAL1), supporting that paternal UBE3A expression in the SCN is often of neuronal origin. Paternal UBE3A also partially colocalizes with a marker of neural progenitors, SOX2, implying that relaxed or incomplete imprinting of paternal Ube3a reflects an overall immature molecular phenotype. Our findings highlight the complexity of Ube3a imprinting in the brain and illuminate a subpopulation of SCN neurons as a focal point for future studies aimed at understanding the mechanisms of Ube3a imprinting. PMID:27306933

  5. Corticotropin-releasing Factor in the Dorsal Raphe Nucleus: Linking Stress Coping and Addiction

    PubMed Central

    Valentino, Rita J.; Lucki, Irwin; Van Bockstaele, Elisabeth

    2009-01-01

    Addiction and stress are linked at multiple levels. Drug abuse is often initiated as a maladaptive mechanism for coping with stress. It is maintained in part by negative reinforcement to prevent the aversive consequences of stress associated with abstinence. Finally, stress is a major factor leading to relapse in subjects in which drug seeking behavior has extinguished. These associations imply overlapping or converging neural circuits and substrates that underlie the processes of addiction and the expression of the stress response. Here we discuss the major brain serotonin (5-HT) system, the dorsal raphe nucleus (DRN)-5-HT system as a point of convergence that links these processes and how the stress-related neuropeptide, corticotropin-releasing factor (CRF) directs this by a bimodal regulation of DRN neuronal activity. The review begins by describing a structural basis for CRF regulation of the DRN-5-HT system. This is followed by a review of the effects of CRF and stress on DRN function based on electrophysiological and microdialysis studies. The concept that multiple CRF receptor subtypes in the DRN facilitate distinct coping behaviors is reviewed with recent evidence for a unique cellular mechanism by which stress history can determine the type of coping behavior. Finally, work on CRF regulation of the DRN-5-HT system is integrated with literature on the role of 5-HT-dopamine interactions in addiction. PMID:19800322

  6. RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles

    PubMed Central

    Keebaugh, Alaine C.; Barrett, Catherine E.; LaPrairie, Jamie L.; Jenkins, Jasmine J.; Young, Larry J.

    2015-01-01

    Oxytocin modulates many aspects of social cognition and behaviors, including maternal nurturing, social recognition and bonding. Natural variation in oxytocin receptor (OXTR) density in the nucleus accumbens (NAcc) is associated with variation in alloparental behavior, and artificially enhancing OXTR expression in the NAcc enhances alloparental behavior and pair bonding in socially monogamous prairie voles. Furthermore, infusion of an OXTR antagonist into the nucleus accumbens (NAcc) inhibits alloparental behavior and partner preference formation. However, antagonists can promiscuously interact with other neuropeptide receptors. To directly examine the role of OXTR signaling in social bonding, we used RNA interference to selectively knockdown, but not eliminate, OXTR in the NAcc of female prairie voles and examined the impact on social behaviors. Using an adeno-associated viral vector expressing a short hairpin RNA (shRNA) targeting Oxtr mRNA, we reduced accumbal OXTR density in female prairie voles from juvenile age through adulthood. Females receiving the shRNA vector displayed a significant reduction in alloparental behavior and disrupted partner preference formation. These are the first direct demonstrations that OXTR plays a critical role in alloparental behavior and adult social attachment, and suggest that natural variation in OXTR expression in this region alone can create variation in social behavior. PMID:25874849

  7. The Drosophila neuropeptides PDF and sNPF have opposing electrophysiological and molecular effects on central neurons.

    PubMed

    Vecsey, Christopher G; Pírez, Nicolás; Griffith, Leslie C

    2014-03-01

    Neuropeptides have widespread effects on behavior, but how these molecules alter the activity of their target cells is poorly understood. We employed a new model system in Drosophila melanogaster to assess the electrophysiological and molecular effects of neuropeptides, recording in situ from larval motor neurons, which transgenically express a receptor of choice. We focused on two neuropeptides, pigment-dispersing factor (PDF) and small neuropeptide F (sNPF), which play important roles in sleep/rhythms and feeding/metabolism. PDF treatment depolarized motor neurons expressing the PDF receptor (PDFR), increasing excitability. sNPF treatment had the opposite effect, hyperpolarizing neurons expressing the sNPF receptor (sNPFR). Live optical imaging using a genetically encoded fluorescence resonance energy transfer (FRET)-based sensor for cyclic AMP (cAMP) showed that PDF induced a large increase in cAMP, whereas sNPF caused a small but significant decrease in cAMP. Coexpression of pertussis toxin or RNAi interference to disrupt the G-protein Gαo blocked the electrophysiological responses to sNPF, showing that sNPFR acts via Gαo signaling. Using a fluorescent sensor for intracellular calcium, we observed that sNPF-induced hyperpolarization blocked spontaneous waves of activity propagating along the ventral nerve cord, demonstrating that the electrical effects of sNPF can cause profound changes in natural network activity in the brain. This new model system provides a platform for mechanistic analysis of how neuropeptides can affect target cells at the electrical and molecular level, allowing for predictions of how they regulate brain circuits that control behaviors such as sleep and feeding. PMID:24353297

  8. Sex dimorphism in the avian arginine vasotocin system with special emphasis to the bed nucleus of the stria terminalis.

    PubMed

    Grossmann, Roland; Jurkevich, Aleksandr; Köhler, Almut

    2002-04-01

    The avian neuropeptide arginine vasotocin (AVT) originally characterized as the antidiuretic hormone (, Endocrinol. 66, 860-871) is produced by neurosecretory cells within the brain. Numerous neuroanatomical studies that employed immunocytochemical and in situ hybridization techniques revealed such cells in the following anatomical brain locations: (a) preoptic area including supraoptic nucleus; (b) paraventricular nucleus; (c) the bed nucleus of the stria terminalis (BnST) (, J. Hirnforsch. 27, 559-566;, J. Neuroendcrinol. 5, 281-288;, Cell Tiss. Res. 287, 69-77;, J. Comp. Neurol. 369, 141-157). The BnST which influences reproduction and sexual behavior shows sex differences in morphology, steroid responsiveness and synthesis of neuropeptides including AVT (, Brain Res. 657, 171-184). AVT is the main endocrine regulator of fluid balance in avian species and, in addition, is involved in oviposition in these species. Our recent studies clearly demonstrated that AVT secretion after osmotic stimulation is sexually dimorphic. In order to investigate whether AVT is expressed and synthesized in the BnST in a sexually dimorphic manner we have used in situ hybridization technique and immunocytochemistry to analyze AVT gene expressing neurons in the parvocellular (small-celled nulei) BnST of adult male and female chickens. In cocks, AVT peptide-containing neurons were detected in the parvocellular BnST and the lateral septal area, whereas no AVT immunoreactive neurons were detected in the corresponding regions of the hen. Even after osmotic stimulation AVT gene expression in neurons of the parvocellular BnST of hens was not upregulated (, Cell Tiss. Res. 287, 69-77). These results demonstrate: (a) AVT gene expression in the BnST of chickens; and (b) a strong sexual dimorphism in this region. Furthermore, AVT synthesis is regulated on the transcriptional level independent from osmotic stimuli. Thus, sex steroids might be the main regulator of AVT gene expression in the Bn

  9. Injury of the Arcuate Fasciculus in the Dominant Hemisphere in Patients With Mild Traumatic Brain Injury: A Retrospective Cross-Sectional Study.

    PubMed

    Jang, Sung Ho; Lee, Ah Young; Shin, So Min

    2016-03-01

    Little is known about injury of the arcuate fasciculus (AF) in patients with mild traumatic brain injury (TBI). We investigated injury of the AF in the dominant hemisphere in patients with mild TBI, using diffusion tensor tractography (DTT). We recruited 25 patients with injury of the left AF among 64 right-handed consecutive patients with mild TBI and 20 normal control subjects. DTTs of the left AF were reconstructed, and fractional anisotropy (FA), apparent diffusion coefficient (ADC), and fiber number of the AF were measured. Among 64 consecutive patients, 25 (39%) patients showed injury of the left AF. The patient group showed lower FA value and fiber number with higher ADC value than the control group (P < 0.05). On K-WAB evaluation, aphasia quotient and language quotient were 95.9 ± 4.1 (range 85-100) and 95.0 ± 5.4 (range 80-100), respectively. However, 23 (92.0%) of 25 patients complained of language-related symptoms after TBI; paraphasia in 12 (48.0%) patients, deficits of comprehension in 4 (16.0%) patients, deficits of speech production in 1 (4.0%) patient, and >2 language symptoms in 6 (24.0%) patients. We found that a significant number (39%) of patients with mild TBI had injury of the AF in the dominant hemisphere and these patients had mild language deficit. These results suggest that DTT could provide useful information in detecting injury of the AF and evaluation of the AF using DTT would be necessary even in the case of a patient with mild TBI who complains of mild language deficit. PMID:26945425

  10. Reconstruction of the arcuate fasciculus for surgical planning in the setting of peritumoral edema using two-tensor unscented Kalman filter tractography

    PubMed Central

    Chen, Zhenrui; Tie, Yanmei; Olubiyi, Olutayo; Rigolo, Laura; Mehrtash, Alireza; Norton, Isaiah; Pasternak, Ofer; Rathi, Yogesh; Golby, Alexandra J.; O'Donnell, Lauren J.

    2015-01-01

    Background Diffusion imaging tractography is increasingly used to trace critical fiber tracts in brain tumor patients to reduce the risk of post-operative neurological deficit. However, the effects of peritumoral edema pose a challenge to conventional tractography using the standard diffusion tensor model. The aim of this study was to present a novel technique using a two-tensor unscented Kalman filter (UKF) algorithm to track the arcuate fasciculus (AF) in brain tumor patients with peritumoral edema. Methods Ten right-handed patients with left-sided brain tumors in the vicinity of language-related cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-Tesla magnetic resonance imaging (MRI) including a diffusion-weighted dataset with 31 directions. Fiber tractography was performed using both single-tensor streamline and two-tensor UKF tractography. A two-regions-of-interest approach was applied to perform the delineation of the AF. Results from the two different tractography algorithms were compared visually and quantitatively. Results Using single-tensor streamline tractography, the AF appeared disrupted in four patients and contained few fibers in the remaining six patients. Two-tensor UKF tractography delineated an AF that traversed edematous brain areas in all patients. The volume of the AF was significantly larger on two-tensor UKF than on single-tensor streamline tractography (p < 0.01). Conclusions Two-tensor UKF tractography provides the ability to trace a larger volume AF than single-tensor streamline tractography in the setting of peritumoral edema in brain tumor patients. PMID:26082890

  11. Both Estrogen and Androgen Modify the Response to Activation of Neurokinin-3 and κ-Opioid Receptors in Arcuate Kisspeptin Neurons From Male Mice.

    PubMed

    Ruka, Kristen A; Burger, Laura L; Moenter, Suzanne M

    2016-02-01

    Gonadal steroids regulate the pattern of GnRH secretion. Arcuate kisspeptin (kisspeptin, neurokinin B, and dynorphin [KNDy]) neurons may convey steroid feedback to GnRH neurons. KNDy neurons increase action potential firing upon the activation of neurokinin B receptors (neurokinin-3 receptor [NK3R]) and decrease firing upon the activation of dynorphin receptors (κ-opioid receptor [KOR]). In KNDy neurons from intact vs castrated male mice, NK3R-mediated stimulation is attenuated and KOR-mediated inhibition enhanced, suggesting gonadal secretions are involved. Estradiol suppresses spontaneous GnRH neuron firing in male mice, but the mediators of the effects on firing in KNDy neurons are unknown. We hypothesized the same gonadal steroids affecting GnRH firing pattern would regulate KNDy neuron response to NK3R and KOR agonists. To test this possibility, extracellular recordings were made from KNDy neurons in brain slices from intact, untreated castrated or castrated adult male mice treated in vivo with steroid receptor agonists. As observed previously, the stimulation of KNDy neurons by the NK3R agonist senktide was attenuated in intact vs castrated mice and suppression by dynorphin was enhanced. In contrast to observations of steroid effects on the GnRH neuron firing pattern, both estradiol and DHT suppressed senktide-induced KNDy neuron firing and enhanced the inhibition caused by dynorphin. An estrogen receptor-α agonist but not an estrogen receptor-β agonist mimicked the effects of estradiol on NK3R activation. These observations suggest the steroid modulation of responses to activation of NK3R and KOR as mechanisms for negative feedback in KNDy neurons and support the contribution of these neurons to steroid-sensitive elements of a GnRH pulse generator. PMID:26562263

  12. A Newly Recognized, 460 km Long and Arcuate, Right-Lateral Strike-Slip Fault Traversing Puerto Rico and the Virgin Islands

    NASA Astrophysics Data System (ADS)

    Loureiro, P.; Mann, P.

    2014-12-01

    We use 830 km of seismic reflection lines and 94,000 km2 of high-resolution multibeam bathymetry to identify a 460-km-long and semi-arcuate strike-slip fault that can be traced to the southwest from the Mona rift west of Puerto, across the onland area of south-central Puerto Rico (Cerro Goden and Great Southern Puerto Rico fault zones), across the Whiting basin southeast of Puerto Rico, across the Virgin Islands basin and to the northeast along the Anegada Passage and Tortola ridge. On multibeam and seismic reflection data the fault is active based on a continuous seafloor scarp ranging in height from 10 to 40 m. Seismic profiles show that the fault is alternatively downthrown to the north and south typical of strike-slip faults. The sense of most recent strike-slip offset on the fault is right-lateral based on offsets at 4 localities that range from 1.5 to3.5 km. Shallow earthquake swarms are associated with the fault trace in the Virgin Islands area but large segments of the fault are aseismic and appear locked. We propose that this fault system forms the southern boundary of an actively CCW-rotating Puerto Rico microplate that is driven by oblique, left-lateral shear of the North America-Caribbean plate boundary. The northern edge of the microplate is inferred to follow left-lateral faults known in the Puerto Rico trench (Bunce and Bowin fault zones) that close the loop around the crudely circular microplate in the area of the Mona rift. We have modeled these boundaries of the rotating block using the Defnode method of finite elements constrained by GPS and earthquake slip vectors.

  13. Horizontal portion of arcuate fasciculus fibers track to pars opercularis, not pars triangularis, in right and left hemispheres: A DTI study

    PubMed Central

    Kaplan, Elina; Naeser, Margaret A.; Martin, Paula I.; Ho, Michael; Wang, Yunyan; Baker, Errol; Pascual-Leone, Alvaro

    2010-01-01

    The arcuate fasciculus (AF) is a white matter pathway traditionally considered to connect left Broca’s area with posterior language zones. We utilized diffusion tensor imaging (DTI) in eight healthy subjects (5M) to track pathways in the horizontal mid-portion of the AF (hAF) to subregions of Broca’s area - pars triangularis (PTr) and pars opercularis (POp); and to ventral premotor cortex (vPMC) in the right and left hemispheres (RH, LH). These pathways have previously been studied in the LH, but not in the RH. Only 1/8 subjects showed fiber tracts between PTr and hAF in the RH (also, only 1/8 in the LH). In contrast to PTr, 5/8 subjects showed fiber tracts between POp and hAF in the RH (8/8 in the LH). Fiber tracts for vPMC were similar to those of POp, where 7/8 subjects showed fiber tracts between vPMC and hAF in the RH (8/8 in the LH). Our designated hAF could have included some of the superior longitudinal fasciculus (SLF) III, because it is difficult to separate the two fiber bundles. The SLF III has been previously reported to connect supramarginal gyrus with POp and vPMC in the LH. Thus, although the present DTI study showed almost no pathways between PTr and hAF in the RH (and in the LH), robust pathways were observed between POp and/or vPMC with hAF in the RH (and in LH). These results replicate previous studies for the LH, but are new, for the RH. They could contribute to better understanding of recovery in aphasia. PMID:20438853

  14. Neuropeptide Substance-P-Conjugated Chitosan Nanofibers as an Active Modulator of Stem Cell Recruiting

    PubMed Central

    Kim, Min Sup; Park, Sang Jun; Cho, Wheemoon; Gu, Bon Kang; Kim, Chun-Ho

    2016-01-01

    The goal to successful wound healing is essentially to immobilize and recruit appropriate numbers of host stem or progenitor cells to the wound area. In this study, we developed a chitosan nanofiber-immobilized neuropeptide substance-P (SP), which mediates stem cell mobilization and migration, onto the surfaces of nanofibers using a peptide-coupling agent, and evaluated its biological effects on stem cells. The amount of immobilized SP on chitosan nanofibers was modulated over the range of 5.89 ± 3.27 to 75.29 ± 24.31 ng when reacted with 10 to 500 ng SP. In vitro migration assays showed that SP-incorporated nanofibers induced more rapid migration of human mesenchymal stem cells on nanofibers compared to pristine samples. Finally, the conjugated SP evoked a minimal foreign body reaction and recruited a larger number of CD29- and CD44-positive stem cells into nanofibers in a mouse subcutaneous pocket model. PMID:26751441

  15. Neuropeptide Substance-P-Conjugated Chitosan Nanofibers as an Active Modulator of Stem Cell Recruiting.

    PubMed

    Kim, Min Sup; Park, Sang Jun; Cho, Wheemoon; Gu, Bon Kang; Kim, Chun-Ho

    2016-01-01

    The goal to successful wound healing is essentially to immobilize and recruit appropriate numbers of host stem or progenitor cells to the wound area. In this study, we developed a chitosan nanofiber-immobilized neuropeptide substance-P (SP), which mediates stem cell mobilization and migration, onto the surfaces of nanofibers using a peptide-coupling agent, and evaluated its biological effects on stem cells. The amount of immobilized SP on chitosan nanofibers was modulated over the range of 5.89 ± 3.27 to 75.29 ± 24.31 ng when reacted with 10 to 500 ng SP. In vitro migration assays showed that SP-incorporated nanofibers induced more rapid migration of human mesenchymal stem cells on nanofibers compared to pristine samples. Finally, the conjugated SP evoked a minimal foreign body reaction and recruited a larger number of CD29- and CD44-positive stem cells into nanofibers in a mouse subcutaneous pocket model. PMID:26751441

  16. Analytic framework for peptidomics applied to large-scale neuropeptide identification.

    PubMed

    Secher, Anna; Kelstrup, Christian D; Conde-Frieboes, Kilian W; Pyke, Charles; Raun, Kirsten; Wulff, Birgitte S; Olsen, Jesper V

    2016-01-01

    Large-scale mass spectrometry-based peptidomics for drug discovery is relatively unexplored because of challenges in peptide degradation and identification following tissue extraction. Here we present a streamlined analytical pipeline for large-scale peptidomics. We developed an optimized sample preparation protocol to achieve fast, reproducible and effective extraction of endogenous peptides from sub-dissected organs such as the brain, while diminishing unspecific protease activity. Each peptidome sample was analysed by high-resolution tandem mass spectrometry and the resulting data set was integrated with publically available databases. We developed and applied an algorithm that reduces the peptide complexity for identification of biologically relevant peptides. The developed pipeline was applied to rat hypothalamus and identifies thousands of neuropeptides and their post-translational modifications, which is combined in a resource format for visualization, qualitative and quantitative analyses. PMID:27142507

  17. Sleep-active neuron specification and sleep induction require FLP-11 neurope