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Sample records for agouti dasyprocta leporina

  1. The role of seed mass on the caching decision by agoutis, Dasyprocta leporina (Rodentia: Agoutidae

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    Mauro Galetti

    2010-06-01

    Full Text Available It has been shown that the local extinction of large-bodied frugivores may cause cascading consequences for plant recruitment and overall plant diversity. However, to what extent the resilient mammals can compensate the role of seed dispersal in defaunated sites is poorly understood. Caviomorph rodents, especially Dasyprocta spp., are usually resilient frugivores in hunted forests and their seed caching behavior may be important for many plant species which lack primary dispersers. We compared the effect of the variation in seed mass of six vertebrate-dispersed plant species on the caching decision by the red-rumped agoutis Dasyprocta leporina Linnaeus, 1758 in a land-bridge island of the Atlantic forest, Brazil. We found a strong positive effect of seed mass on seed fate and dispersal distance, but there was a great variation between species. Agoutis never cached seeds smaller than 0.9 g and larger seeds were dispersed for longer distances. Therefore, agoutis can be important seed dispersers of large-seeded species in defaunated forests.

  2. Interactions Among Different Devices and Electrical Stimulus on the Electroejaculation of Captive Agoutis (Dasyprocta leporina).

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    Castelo, T S; Souza, A L P; Lima, G L; Peixoto, G C X; Campos, L B; Oliveira, M F; Silva, A R

    2015-06-01

    The interactions among different electroejaculation devices associated with serial or continuous stimuli were investigated to improve the efficiency of the electroejaculation for semen collection in agoutis. Ten sexually matured male Dasyprocta leporina were restrained by the intramuscular administration of xylazine-ketamine association. Each individual was randomly subjected to four electroejaculation protocols, by combining two devices (one presenting longitudinal electrodes emitting square waves and other presenting ring electrodes emitting sine waves) and two electrical stimuli protocols (serial or continuous). A total of 40 attempts for electroejaculation were conducted in agoutis, being 10 per treatment. The most efficient treatment in providing ejaculates containing sperm (p electroejaculator connected to a probe with ring electrodes and associated with serial stimuli (4/7; 57%). In spite of semen parameters obtained by sine waves were adequate for using the samples for assisted reproduction, higher values for sperm motility and functional membrane integrity were obtained in the use of the square wave, independently of the electric stimulation protocol used (p electroejaculation in adults D. leporina. PMID:25800458

  3. Liquid and Frozen Storage of Agouti (Dasyprocta leporina) Semen Extended with UHT Milk, Unpasteurized Coconut Water, and Pasteurized Coconut Water

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    Garcia, G. W.; Mollineau, W. M.; Adogwa, A. O.

    2010-01-01

    This study evaluated the effects of semen extension and storage on forward progressive motility % (FPM%) in agouti semen. Three extenders were used; sterilized whole cow's milk (UHT Milk), unpasteurized (CW) and pasteurized coconut water (PCW), and diluted to 50, 100, 150, and 200 × 106 spermatozoa/ml. Experiment 1: 200 ejaculates were extended for liquid storage at 5 ∘ C and evaluated every day for 5 days to determine FPM% and its rate of deterioration. Experiment 2: 150 ejaculates were exte...

  4. Habitat use and relative abundance of the Spotted Paca Cuniculus paca (Linnaeus, 1766 (Rodentia: Cuniculidae and the Red-rumped Agouti Dasyprocta leporina (Linnaeus, 1758 (Rodentia: Dasyproctidae in Guatopo National Park, Venezuela

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    Elinor Jax

    2015-01-01

    Full Text Available The Spotted Paca Cuniculus paca and the Red-rumped Agouti Dasyprocta leporina are affected by habitat loss and hunting.  In Venezuela, their conservation status is unknown, even within protected areas.  The objective of this study was to estimate the relative abundance, activity patterns, habitat use, and effect of human activities on these species in Venezuela.  To achieve this, 26 camera-trap stations (20.8km2 were established in Guatopo National Park between February and April 2011, characterization of the habitat was undertaken and occupancy models were created.  The relative abundance of the Spotted Paca was 1.62 captures/100trap-nights, with a fully nocturnal activity pattern.  The relative abundance of the Red-rumped Agouti was 2.32 captures/100trap-nights, with a pronounced diurnal activity pattern. The occupation probability of the Red-rumped Agouti (0.61 SE 0.02 was higher than that of the Spotted Paca (0.27 SE 0.02. Spotted Pacas were mainly found in areas with mature forest and high tree density, whereas the  Red-rumped Agoutis were most frequently found in valleys with little disturbed forest.  A positive correlation was found between illegal hunting activities and areas occupied by the Spotted Paca.  It is important to strengthen the park control measurements to reduce illegal hunting of Spotted Pacas.

  5. Parasitism of two zoonotic reservoirs Dasyprocta leporina and D. fuliginosa (Rodentia from Amazonas, with Trichostrongylina nematodes (Heligmonellidae: description of a new genus and a new species

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    Alessandra Queiroga Gonçalves

    2007-09-01

    Full Text Available A new genus and a new species of Heligmonellidae nematodes are described parasiting the stomach of three agoutis (two Dasyprocta fuliginosa and one D. leporina captured in the middle and high Negro river microregion, state of Amazonas, Brazil. The new genus, as well as its type-species, are closely related to the trichostrongylids included in Fuellebornema, particularly on what concerns the pattern of the caudal bursa, but differing from them by the characteristics of the synlophe, that presents a poorly developed carene, when compared to the referred number of body ridges in Freitastrongylus n. gen. and consequently in F. angelae n. sp.,in which the ridges are well developed and the carene at mid-body has a similar size when compared to the ridge situated in front of the right field (ridge no. 5. Caudal bursa is of the type 1-4, with rays 9 shorter than rays 10, with a very long genital cone.

  6. Macroscopic description of teeth of Azara's agouti (Dasyprocta azarae

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    Fabrício S. Oliveira

    2012-01-01

    Full Text Available The teeth of Azara's agouti (Dasyprocta azarae were described macroscopically in order to provide biological data on one of the largest wild rodents of the Americas. Radiography was taken on six heads and the teeth were described. Enamel surrounds the coronal dentin, projects to the roots and is present as parallel inner laminae in buccolingual direction. The dentin is located among the enamel laminae and surrounds the pulp horns. The cementum is located internally to the enamel laminae. On the lingual surface, the cementum and dentin are the outer elements.

  7. Monitoramento do ciclo estral de cutias (Dasyprocta leporina Lichtenstein, 1823 através de citologia esfoliativa vaginal e ultrassonografia

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    Lívia B. Campos

    2015-02-01

    Full Text Available O objetivo deste estudo foi monitorar o ciclo estral em cutias (Dasyprocta leporina criadas em cativeiro no semiárido brasileiro. Durante 70 dias, cinco cutias foram diariamente submetidas a citologia esfoliativa vaginal, e o monitoramento ultrassonográfico ovariano foi realizado a cada três dias. Um total de 8 ciclos estrais foi completamente monitorado, com duração de 28,2±0,7 dias, variando de 24 a 31 dias. Pela citologia esfoliativa vaginal, houve uma predominância de células superficiais nas fases de proestro e estro (P0,05. Os folículos foram identificados durante as fases estrogênicas (proestro e estro, com diâmetro médio de 1±0,5mm. Em apenas 12,5% das fases luteais, corpos lúteos medindo 1,4±0,9mm foram identificados. Conclui-se que a associação da citologia vaginal e da ultrassonografia ovariana constitui uma alternativa viável para o monitoramento de ciclos estrais e identificação das fases estrogênicas em cutias da espécie Dasyprocta leporina

  8. Fatal anemia and dermatitis in captive agoutis (Dasyprocta mexicana) infested with Echidnophaga fleas.

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    Cucchi-Stefanoni, Karina; Juan-Sallés, Carles; Parás, Alberto; Garner, Michael M

    2008-08-17

    Two captive agoutis (Dasyprocta mexicana) died of anemia with centrilobular hepatocellular necrosis (2/2), severe flea ectoparasitism (2/2), and cardiomegaly attributed to anemia (1/2). Other agoutis were similarly parasitized and one had anemia. Fleas were manually removed and all agoutis treated topically with propoxur and selamectin and moved to another enclosure. No additional cases of fatal anemia were seen. Cutaneous lesions suggestive of hypersensitivity were observed in three additional agoutis with dorsal alopecia (3/3), a penetrating wound associated with pruritus and self-mutilation in the flank (2/3), flea ectoparasitism at the time of morphologic diagnosis (1/3), and hyperplastic perivascular dermatitis (3/3). One of these died of bacterial infection of the wound. Similar but milder skin disease was seen in 3 out of over 30 maras (Dolichotis patagonum) housed in the same exhibit. Fleas collected from all the fatal agouti cases and maras were classified in the genus Echidnophaga based on the angular front margin of head, contracted thorax, absence of genal and pronotal combs, and the fact that fleas did not jump. These findings suggest that flea ectoparasitism may be an important cause of morbidity and mortality in captive rodents. PMID:18556127

  9. The subplacenta of the red-rumped agouti (Dasyprocta leporina L)

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    Rodrigues, Rosangela Felipe; Carter, Anthony M.; Ambrosio, Carlos Eduardo;

    2006-01-01

    electron microscopy. In addition, to study the microvasculature of the subplacenta, vessel casts were inspected by scanning electron microscopy. RESULTS: In the subplacenta, lamellae of connective tissue support a layer of mononuclear cytotrophoblast cells. Beneath this is found syncytiotrophoblast....... Clusters of multinuclear giant cells occur in the transition zone between the subplacenta and decidua. There are prominent intercellular spaces between the cytotrophoblast cells. The basal membrane of these cells is often close to fetal blood vessels. The syncytiotrophoblast surrounds an extensive system...... of lacunae. Microvilli project into these lacunae from the plasma membrane of the syncytiotrophoblast. The syncytial cytoplasm contains electron-dense granules. This is probably the amylase-resistant PAS-positive material identified by histochemistry. The subplacenta is supplied entirely from the fetal...

  10. Segmentos anátomo-cirúrgicos arteriais do rim de cutia (Dasyprocta prymnolopha Anatomical-surgical arterial segments of the kidney in agouti (Dasyprocta prymnolopha

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    Maria A.M. Carvalho

    2008-05-01

    Full Text Available Foram estudados 20 pares de rins decutias (Dasyprocta prymnolopha Wagler, 1831, com o objetivo de descrever os segmentos anátomo-cirúrgicos arteriais. As artérias renais foram injetadas com solução de Vinilite corada, e os rins foram submetidos à corrosão ácida para a obtenção dos moldes vasculares. Observou-se que as artérias renais da cutia, sempre únicas, dividiram-se em artéria setorial ventral e artéria setorial dorsal, caracterizando dois setores renais separados por plano avascular. As artérias setoriais penetraram no hilo renal (100% dos casos. Estes vasos deram origem aos ramos segmentares responsáveis pela irrigação de territórios independentes em cada setor, os segmentos arteriais renais. No rim direito foram observados 3 (60%, 4 (35% e 5 segmentos (5% no setor arterial ventral e 3 (30%, 4 (45%, 5 (20% e 6 (5% segmentos no setor dorsal e, à esquerda, 2(10%, 3 (55% e 4 (35% segmentos no setor ventral e 3 (25%, 4 (50% e 5 (25% no dorsal. Com base na distribuição arterial nos rins de cutia, observaram-se setores e segmentos arteriais independentes, sendo possível, desta forma, a realização de setoriectomia e segmentectomia nesta espécie.Twenty pairs of agouti (Dasyprocta prymnolopha Wagler, 1831 kidneys were studied to describe the arterial anatomical-surgical segments. The renal arteries were injected with stained acetate vinyl, followed by procedures of acid corrosion in order to obtain vascular casts. It was found that the renal artery is always single and bifurcated into ventral and dorsal sectorial arteries. The sectorial arteries reached the kidneys (100% of the cases through the hilus. These vessels gave origin to segmental branches responsible for kidney irrigation. At the right kidney, the ventral sectorial arteries gave origin to 3 (60% of the cases, 4 (35% and 5 (5% segmental branches; the dorsal sectorial arteries gave origin to 3 (30%, 4 (45%, 5 (20% and 6 (5% segmental arteries separated by a

  11. Infección inducida en el roedor selvático Dasyprocta leporina (Rodentia: Dasyproctidae, con huevos larvados de Lagochilascaris minor (Nematoda: Ascarididae Induced infection in the wild rodent Dasyprocta leporina (Rodentia: Dasyproctidae with larval eggs of Lagochilascaris minor (Nematoda: Ascarididae

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    S. Gregorio

    1990-12-01

    Full Text Available Ejemplares de Dasyprocta leporina Linnaeus, 1758 fueron criados alejados de su ambiente natural. A los 3 ó 4 meses de edad, se los inoculó por vía oral con huevos de Lagochilascaris minor Leiper, 1909 obtenidos de una paciente nativa. Los huevos se los incubó por más de 80 dias, para que de ellos fuese posible obtener por compresión mecánica, larvas que se mantuviesen vivas en medio acuoso por 48 horas o más. Sacrificados los animales a los 14 ó 46 dias posteriores a la infección, se hallaron en los músculos esqueléticos larvas ovilladas dentro de nódulos inflamatorios, los cuales no presentaban reacción a cuerpo extraño, abscedación o calcificación. El desarollo de los nódulos no parecía afectar la normalidad de los hospedadores. Las larvas obtenidas eran similares a las descritas por SPRENT como de tercer estadio para estos helmintos. Ratones blancos infectados con material similar, no presentaron nódulos en sus músculos ni se pudo recuperar de sus tejidos larva alguna. Por los hallazgos obtenidos con la infección de estos animales, se postula que el helminto no posee ciclo pulmonar y que su desarrollo requiere de un hospedador intermediario.Specimens of Dasyprocta leporina (Linnaeus, 1758 were raised out their natural environment. At three to four months of age they were orally inoculated with Lagochilascaris minor (Leiper, 1909 eggs obtained from a native patient. The eggs were incubated for more than 80 days so that it was possible to obtain, by mechanical compression, larvae that could be maintained alive in liquid medium for 48 hours or more. The animals were sacrificed 14-46 days after infection and tangled larva in inflammatory nodules were found in skeletal muscle without foreign body reaction, abscess formation or calcification. The development of the nodules did not seem to affect the hosts. The larvae obtained were similar to those described by SPRENT as the third stage of these helminths. When white mice were

  12. Electrocardiogram assessment in non-anaesthetized clinically healthy agouti (Dasyprocta primnolopha, Wagler 1831

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    Anaemilia das N. Diniz

    2013-12-01

    Full Text Available The agouti is one of the most intensely hunted species throughout the Amazon and the semiarid regions of north-eastern Brazil. Considering the current tendency of wild animal management in captivity, the objective of this study was to determine heart reference values for agouti raised in captivity, based on electrocardiographic assessments (ECG. Adult agouti were selected without clinical signs of heart disease (n=30. The animals were restrained physically and then the ECG was performed. Standardized measurements were taken to establish the statistical analysis of the data. Analysis of the QRS complex showed values compatible with previous reports in peer animals and the limited data available for other wild and exotic species, except for the T wave that showed similar amplitude to the R wave in all the animals studied. The data obtained provided the first reference values for ECG tracings in agouti, contributing to a better understanding of heart electrophysiology in identifying myocardial pathology in these animals.

  13. The organization of the brainstem nuclei associated with the vagus nerve in the Agouti (Dasyprocta leporina). A neurohistological study.

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    Phillips, C M; Odekunle, A

    2011-01-01

    A total of six adult animals were used for the study. Following anaesthesia via intraperitoneal injection of a mixture of ketamin and bombazine in ratio 2:1, thoracotomy was performed to exteriorize the heart for intracardial perfusion. The perfusion canular was inserted into the left ventricle and animal perfused sequentially with normal saline and 10% formal saline. Following perfusion, craniotomy was performed to remove the entire brain along with the upper segments of the spinal cord. The brain specimen was then dehydrated, cleared and infiltrated with paraffin wax. The specimen was then cut in 15 micron thick serial sections. The sections were then processed for neurohistological analyses using a Nikon microscope to which was attached Nikon camera. Analyses of the sections revealed bilateral representation of the dorsal motor nucleus of the vagus nerve in the medulla oblongata. The nucleus ambiguus, nucleus of the tractus solitarius, hypoglossal nucleus and the area postrema were also identified in the medulla oblongata. The implications of our findings are discussed in the text of the article.

  14. Colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae Semen collection by electroejaculation in Azara´s agouti (Dasyprocta azarae

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    Antonio C. Martinez

    2013-01-01

    Full Text Available As cutias são animais que vivem nas Américas Central e do Sul, com potencial zootécnico e que despertam crescente interesse científico. O objetivo deste estudo foi estabelecer um padrão para colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae. Foram utilizados machos adultos (n=4 anestesiados e submetidos a quatro séries de 20 estímulos eletroejaculatórios, com 3 segundos de duração cada, com uma intensidade de 2, 4, 6 e 8 volts, com dois minutos de intervalo entre cada série. A colheita de sêmen foi obtida em todos os animais, com ereção parcial com 2 volts, ereção evidente com 4 volts, ejaculação com 6 volts e exacerbação da glande e exteriorização das espículas penianas com 8 volts, observando-se espermatozoides em 100% das amostras. A técnica descrita para colheita de sêmen em cutia-parda foi eficaz.Agoutis are animals that live in South and Central America, present rearing potential and call increasing scientific interest. The aim of this paper was to establish a model for semen collection by electroejaculation in Azara´s agouti (Dasyprocta azarae. Anesthetized adult males (n=4 were submitted to four series of 20 electroejaculatory stimuli, during 3 seconds each and with 2, 4, 6 and 8 volts, with a 2 minutes rest among series. Semen collection was accomplished in every animal, with partial penis erection at 2 volts, makeable erection at 4 volts, ejaculation at 6 volts, glans and penis spines exposition at 8 volts, and sperm collected in all samples. The described technique for Azara's agouti semen collection was efficient.

  15. Arterial vascularization of the brain of the agouti (Dasyprocta aguti Linnaeus, 1766

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    Roberto Sávio Bessa da Silva

    2016-04-01

    Full Text Available The agouti, a rodent that is geographically distributed throughout South America, is greatly valued for its meat. This paper describes the arterial vascularization of the base of the agouti’s brain, characterizing behavior, and arterial origin and distribution. Ten animals from the Center for the Multiplication of Wild Animals (CEMAS/UFERSA were used and the study was approved by SISBIO (report number 32413- 1 and the Ethics Committee on Animal Use (CEUA/UFERSA (protocol 02/2010. After euthanasia, the animals were incised in the thoracic cavity by an injection of red-stained Neoprene latex 650 and the skulls were subsequently opened. The brains were extracted from the skulls for ventral surface analysis and then fixed in an aqueous 10% formaldehyde solution. The agouti’s arterial vascularization of the brain has two main components, namely the carotid and vertebrobasilar systems. The agouti’s carotid system accounts for vascularization of almost the entire forebrain, while the vertebrobasilar system accounts for vascularization of almost the entire posterior brain (medulla oblongata, pyramid, trapezoid body, cerebellum, bridge, and part of the third caudal section of the forebrain through the caudal cerebral arteries originating from the terminal branches of the basilar artery. The main arteries on the brain surface include the basilar artery, which is unique, and the arterial pairs, specifically the vertebral arteries, cerebellar caudal arteries, trigeminal artery, rostral cerebellar artery, basilar terminal branch artery, cerebral caudal artery, communicating caudal branch of the cerebral carotid artery, cerebral carotid artery, communicating branch rostral cerebral carotid artery, choroidal rostral artery, medial branch of the communicating branch rostral artery, internal ophthalmic artery, middle cerebral artery, and rostral cerebral artery.

  16. Thoracic and heart biometrics of non-anesthetized agouti (Dasyprocta primnolopha Wagler, 1831 measured on radiographic images

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    Anaemilia das N. Diniz

    2013-03-01

    Full Text Available The agouti is a species intensively hunted throughout the Amazon and the semi-arid regions of northeastern Brazil. Considering the current trend in conservation management of wild species, the aim of this study was to determine the morphometric reference to the heart of agouti raised in captivity, based on thoracic and cardiac measurements in these animals. Thirty adult agoutis, 1 to 3 years of age, without clinical signs of cardiac disease were selected. The animals were physically restrained and radiographies in laterolateral (LL and ventrodorsal (VD recumbence were produced. The following measures were taken: the apicobasilar length of the heart (at the most cranial height of the Carina region to the heart apex (AB, maximum width of the heart perpendicular to AB (CD, heart inclination angle (AIC, trachea inclination angle (AIT, distance from the right heart wall (DPTd, distance from the left heart wall (DPTe and vertical depth of the thorax, and the ventral face of the vertebral column to the dorsal border of the sternum at the level of the trachea bifurcation (H. The ratios between AB/CD, AB/H and CD/H were also analyzed. To calculate the vertebral heart scale (VHS, the AB and CD measurements were laid over the thoracic vertebra starting at T4. Radiographic evaluation showed values consistent with those reported in small animals and some wild and exotic species. The main biometric values in the chest cavity and heart of agouti are arranged as follows: (1 The ratios between AB/H ratio and CD/H were not sensitive for identifying heart increases (p>0.05, while the ratio AB/CD was more sensitive in this identification (p<0.05; (2 AIC: 21.2±6.4º (mean between male and famale; (3 AIT for males and females: 9.93±3.23° and 8.4±3.94°; (4 DPTd and DPTe for males: 0.97±0.40cm and 0.7±0.30cm; (5 DPTd and DPTe for females: 1.12±0.42cm and 01.02±0.43cm; (6 VHS for males and females: 7.75±0.48v e 7.61±0.34v; (7 The caudal vena cava (CVC was

  17. Doppler ultrasound of the placenta and maternal and fetal vessels during normal gestation in captive agoutis (Dasyprocta prymnolopha, Wagler, 1831).

    Science.gov (United States)

    Sousa, Francisco C A; Pessoa, Gerson T; Moura, Laecio S; Rodrigues, Renan P S; Diniz, Anaemilia N; Souza, André B; Silva, Elzivânia G; Sanches, Marina P; Silva-Filho, Osmar F; Guerra, Porfirio C; Sousa, João M; Neves, Willams C; Alves, Flávio R

    2016-11-01

    The use of ultrasound for pregnancy monitoring is critical for the evaluation of hemodynamic parameters essential to fetal viability. In the present study, using B-mode and Doppler ultrasound, we characterized the placenta, subplacenta, maternal, and fetal vessels during normal gestation of healthy agoutis raised in captivity. In total, 30 agoutis were obtained from the Center for the Study and Preservation of Wild Animals, Center of Agricultural Sciences, Federal University of Piauí (Núcleo de Estudos e Preservação de Animais Silvestres-NEPAS, Centro de Ciências Agrárias-CCA, Universidade Federal do Piauí-UFPI). These animals were subjected to B-mode and Doppler ultrasound examinations to evaluate their maternal and fetal hemodynamic profiles. The placenta was located in the mesometrial region and had a discoid, ellipsoid, or globular aspect. With spectral Doppler, characteristic systolic and diastolic flow was observed in the umbilical artery. This flow increased during pregnancy. A cross-sectional view revealed a goblet-shaped placenta. The uteroplacental blood flow was characterized by a marked increase in systolic peak velocity during pregnancy, the presence of a rapid deceleration ramp, and a relatively high diastolic speed. The fetal aortic vascular flow was predominantly systolic and diastolic. The caudal vena cava blood flow was characterized by a systolic peak followed by a decreased diastolic wave throughout pregnancy. In the present study, we characterized the morphologic and hemodynamic interactions of the placenta/subplacenta with maternal and fetal vessels in agoutis at 30, 45, 60, 75, and 90 days gestation using B-mode and Doppler ultrasound. We determined the approximation and separation of the blood flow values of the umbilical artery, subplacental flow, uteroplacental artery, fetal aorta, and fetal vena cava. We believe these values may contribute to an understanding of the gestational biology and aid delivery prediction in this species

  18. Isolation, expansion and differentiation of cellular progenitors obtained from dental pulp of agouti (Dasyprocta prymnolopha Wagler, 1831

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    Yulla K.P. de Carvalho

    2015-06-01

    Full Text Available Abstract: The study aimed to isolate, expand, differentiate and characterize progenitor cells existent in the dental pulp of agouti. The material was washed with PBS solution and dissociated mechanically with the aid of a scalpel blade on plates containing culture medium D-MEM/F-12, and incubated at 5% CO2-37⁰C. The growth curve, CFU assay, osteogenic/adipogenic differentiation and characterization were obtained from the isolation. The cells began to be released from the explant tissue around the 7th day of culture. By day 22 of culture, cells reached 80% confluence. At the UFC test, 81 colonies were counted with 12 days of cultivation. The growth curves before and after freezing showed a regular growth with intense proliferation and clonogenic potential. The cell differentiation showed formation of osteoblasts and fat in culture, starting at 15 days of culture in a specific medium. Flow cytometry (FACs was as follows: CD34 (positive, CD14 (negative, CD45 (negative, CD73 (positive, CD79 (negative, CD90 (positive, CD105 (positive, demonstrating high specificity and commitment of isolated cells with mesenchymal stem cells strains. These results suggest the existence of a cell population of stem cells with mesenchymal features from the isolated tissue in the explants of agouti dental pulp, a potential model for study of stem cell strains obtained from the pulp tissue.

  19. Colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae) Semen collection by electroejaculation in Azara´s agouti (Dasyprocta azarae)

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    Antonio C. Martinez; Fabrício S. Oliveira; Cassiana O. Abreu; Leandro L. Martins; Ana P. Pauloni; Nei Moreira

    2013-01-01

    As cutias são animais que vivem nas Américas Central e do Sul, com potencial zootécnico e que despertam crescente interesse científico. O objetivo deste estudo foi estabelecer um padrão para colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae). Foram utilizados machos adultos (n=4) anestesiados e submetidos a quatro séries de 20 estímulos eletroejaculatórios, com 3 segundos de duração cada, com uma intensidade de 2, 4, 6 e 8 volts, com dois minutos de intervalo entre cada...

  20. Morphology of the male agouti accessory genital glands (Dasyprocta prymnolopha Wagler, 1831 Morfologia das glândulas genitais acessórias em cutias (Dasyprocta prymnolopha Wagler, 1831

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    Danilo J. Ayres de Menezes

    2010-09-01

    Full Text Available The morphology of the accessory genital glands of the male agouti was studied in twenty-three animals that were raised in captivity. Twenty animals had their genital glands dissected in situ for macroscopic description. The samples of each gland were recovered, embedded in paraffin, sliced and stained by Hematoxylin-Eosin technique. It was founded four pairs of glands: the vesicular glands, the coagulating glands, the prostate and the bulbourethral glands. Histological characteristics of the vesicular, coagulating and prostate glands showed similar morphology, within the pseudostratified columnar epithelium. The tubulo-alveolar type of the bulbourethral glands showed a lack of connective tissue among the tubules, a small amount of red stained presented it the cytoplasm, and the presence of vacuoles in the tissue. This study concluded that the agouti showed to have similar morphological aspect described in the others species of rodents.A morfologia das glândulas genitais acessórias de cutias foram estudados em 23 animais criados em cativeiros. Vinte animais tiveram suas glândulas genitais dissecadas in situ para as descrições macroscópicas. Para o estudo microscópico foram utilizados três animais. Os fragmentos de cada glândula foram embebidos em parafina, seccionados e corados em hematoxilina e eosina. Foram encontrados quatro pares de glândulas: vesiculares, coaguladoras, próstata e bulbouretrais. As características histológicas da glândula vesicular, coaguladora e próstata mostraram morfologia similar, com epitélio colunar pseudoestratificado. O tipo tuboalveolar da glândula bulbouretral mostrou uma deficiência de tecido conjuntivo, citoplasma pouco corado e presença de vacúolos. Este estudo concluiu que a cutia apresenta as mesmas características morfológicas das glândulas genitais acessórias encontradas em roedores.

  1. Karyotypic analysis in species of the genus Dasyprocta (Rodentia: Dasyproctidae found in Brazilian Amazon

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    ROSEMAR S. L. RAMOS

    2003-03-01

    Full Text Available A total of 30 animals of the genus Dasyprocta were cytogenetically studied. They belong to the following species: D. prymnolopha (N=20, D. leporina (N=6, D. fuliginosa (N=1 and Dasyprocta sp. (N=3 (Dasyproctidae, Hystricognathi. Cell suspensions were obtained by peripheral blood culture, besides bone marrow and spleen cells, from D. prymnolopha and D. leporina. The diploid number was 64/65 for all samples. The karyotypes showed similarity, and chromosomal polymorphism was not detected by Giemsa conventional staining and G banding. The constitutive heterochromatin distribution at the pericentromeric region of all the chromosomes was similar in all species. D. prymnolopha, D. leporina and Dasyprocta sp. presented variation in the heterochromatical block size at one of the homologues of the A18 pair. D. fuliginosa presented the heterochromatin uniformly distributed in all chromosomes. There was not variation in the NORs pattern in the species studied.Foram estudados citogeneticamente um total de 30 animais das espécies D. prymnolopha (N=20, D. leporina (N=6, D. fuliginosa (N=1 e Dasyprocta sp. (N=3 (Dasyproctidae, Histricognathi. As preparações cromossômicas foram obtidas do cultivo de sangue periférico, além de medula óssea e baço em D. prymnolopha e D. leporina. O número diplóide foi de 64/65 em todos os exemplares. O cariótipo mostrou similaridade, não sendo detectado, através de coloração convencional de giemsa e de banda G, polimorfismo cromossômico em qualquer uma das espécies estudadas. A distribuição da heterocromatina constitutiva na região pericentromérica de todos os cromossomos foi similar nas quatro espécies. D. prymnolopha, D. leporina e Dasyprocta sp. apresentaram variação no tamanho do bloco heterocromático em um dos homólogos do par A18. D. fuliginosa apresentou a heterocromatina uniformemente distribuída em todos os cromossomos. Não houve variação no padrão das RONs entre as esp��cies estudadas.

  2. Thoracic and heart biometrics of non-anesthetized agouti (Dasyprocta primnolopha Wagler, 1831 measured on radiographic images Biometria torácica e cardíaca de cutias não anestesiadas (Dasyprocta primnolopha Wagler, 1831 mensuradas em imagens radiográficas

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    Anaemilia das N. Diniz

    2013-03-01

    Full Text Available The agouti is a species intensively hunted throughout the Amazon and the semi-arid regions of northeastern Brazil. Considering the current trend in conservation management of wild species, the aim of this study was to determine the morphometric reference to the heart of agouti raised in captivity, based on thoracic and cardiac measurements in these animals. Thirty adult agoutis, 1 to 3 years of age, without clinical signs of cardiac disease were selected. The animals were physically restrained and radiographies in laterolateral (LL and ventrodorsal (VD recumbence were produced. The following measures were taken: the apicobasilar length of the heart (at the most cranial height of the Carina region to the heart apex (AB, maximum width of the heart perpendicular to AB (CD, heart inclination angle (AIC, trachea inclination angle (AIT, distance from the right heart wall (DPTd, distance from the left heart wall (DPTe and vertical depth of the thorax, and the ventral face of the vertebral column to the dorsal border of the sternum at the level of the trachea bifurcation (H. The ratios between AB/CD, AB/H and CD/H were also analyzed. To calculate the vertebral heart scale (VHS, the AB and CD measurements were laid over the thoracic vertebra starting at T4. Radiographic evaluation showed values consistent with those reported in small animals and some wild and exotic species. The main biometric values in the chest cavity and heart of agouti are arranged as follows: (1 The ratios between AB/H ratio and CD/H were not sensitive for identifying heart increases (p>0.05, while the ratio AB/CD was more sensitive in this identification (pA cutia é uma espécie intensamente caçada em toda a Amazônia e nas regiões semi-áridas do Nordeste do Brasil. Considerando a tendência atual em gestão de conservação das espécies selvagens, o objetivo deste estudo foi determinar referências morfométricas para o coração de cutia criadas em cativeiro, com base em

  3. Seed predation and defleshing in the agouti-dispersed palm Astrocaryum standleyanum

    NARCIS (Netherlands)

    Jansen, Patrick A.; Elschot, Kelly; Verkerk, P. Johannes; Wright, S. Joseph

    2010-01-01

    The agouti (Dasyprocta punctata) meticulously defleshes Astrocaryum standleyanum palm seeds before scatter hoarding. On Barro Colorado Island, Panama, we experimentally tested three hypotheses on how this behaviour could reduce seed predation to the mutual benefit of the tree and the rodent. The fir

  4. Morfologia das glândulas salivares maiores em cutias (Dasyprocta leporina Linnaeus, 1766

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    Carlos M. Oliveira Júnior

    2016-03-01

    Full Text Available Resumo: Estudos acerca da morfologia de animais silvestres servem de subsídio para trabalhos de manejo e preservação de diferentes espécies, pois fornecem informações para a tomada de medidas que auxiliem na manutenção destes em cativeiro, na preservação em habitat natural ou mesmo para ações voltadas a reintrodução ao habitat de origem. Estudos referentes à morfologia de cutias abordam os diversos sistemas, mas nenhum faz referência à arquitetura ou estrutura de suas glândulas salivares. Assim este trabalho objetivou descrever macro e microscopicamente as glândulas salivares maiores de cutias. Foram utilizados dez animais adultos para o desenvolvimento de metodologias relativas à macroscopia propriamente dita das glândulas, microscopia de luz, microscopia eletrônica de transmissão e microscopia eletrônica de varredura. Foram identificadas quatro glândulas salivares maiores nos animais estudados, denominadas parótida, mandibular, zigomática e sublingual. As glândulas apresentaram-se como sendo do tipo tubuloacinares e contendo em seu parênquima ductos dos mais variados tamanhos. Com exceção da glândula parótida, que era estritamente serosa, as demais eram mistas. Da mesma forma, apenas a glândula mandibular foi identificada a presença de ducto do tipo granuloso. Apresentando as cutias os quatro pares de glândulas salivares maiores, estes animais podem servir de modelo para os estudos acerca das mudanças anatômicas sofridas pelos roedores para se adaptar aos diversos habitat do planeta.

  5. Prey refuges as predator hotspots: ocelot (Leopardus pardalis) attraction to agouti (Dasyprocta punctata) dens

    NARCIS (Netherlands)

    Emsens, W.J.; Hirsch, B.T.; Kays, R.; Jansen, P.A.

    2014-01-01

    We tested the hypothesis that prey refuges attract predators, leading to elevated predator activity in the vicinity of refuges. We used camera traps to determine whether the spatial activity of a predator, the ocelot (Leopardus pardalis), was biased toward refuge locations of its principal prey, the

  6. Morfologia da laringe de cutia (Dasyprocta sp.

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    Andrezza B.S. Silva

    2014-06-01

    Full Text Available A cutia (Dasyprocta sp. é um roedor silvestre com distribuição mundial. Atualmente, além de importante papel ecológico que exerce, está sendo utilizada como modelo em experimento animal. Estudos sobre a morfologia destes animais são importantes porque podem ser uma alternativa para o estudo de diversos processos patológicos, além de contribuirem para a preservação da espécie. A laringe é um órgão localizado entre a faringe e a traqueia, no qual está envolvido nas funções de respiração, deglutição e fonação. O presente estudo propôs realizar uma descrição morfológica macroscópica e microscópica da laringe da cutia. Para tanto, foram utilizadas quinze cutias pertencentes ao Centro de Ciências Agrárias da Universidade Federal do Piauí e provenientes do Núcleo de Estudos e Preservação de Animais Silvestres com licença do IBAMA (Nº 02/08-618, CTF Nº 474064. Todos os animais foram identificados, promovida a sexagem e, posteriormente, a laringe acessada e dissecada sendo os fragmentos cartilagíneos encaminhados para rotina histológica e corados pelo método de hematoxilina-eosina. As lâminas obtidas foram visualizadas em microscopia óptica de luz e foto documentadas. A laringe da cutia apresenta cinco cartilagens, com ausência da cartilagem cuneiforme e presença da incisura caudal na cartilagem tireoide. O tecido epitelial da laringe varia de epitélio estratificado pavimentoso queratinizado à não queratinizado e ciliado com células caliciformes.

  7. New records for helminths of hystricognath rodents from the middle and high Rio Negro microregion, State of Amazonas, Brazil Novos registros para helmintos de roedores histricognatos da microrregião do médio e alto Rio Negro, Estado do Amazonas, Brasil

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    Alessandra Q. Gonçalves

    2006-09-01

    Full Text Available Four nematodes and one cestode species from three Brazilian agoutis - two Dasyprocta fuliginosa Wagler, 1832 and one Dasyprocta leporina (Linnaeus, 1758 - and six pacas - Agouti paca (Linnaeus, 1766 - captured in tributaries rivers in the middle and high Rio Negro microregion, State of Amazonas, Brazil, were studied. The nematodes Physaloptera torresi (Travassos, 1920 Ortlepp, 1922, Physocephalus mediospiralis (Molin, 1859 Hall, 1916 and the cestode Raillietina (R. trinitatae (Cameron & Reesal, 1951 Baer & Sandars, 1956 are reported from the State of Amazonas for the first time. The studied helminths (the nematodes P. torresi, P. mediospiralis, Trichuris gracilis (Rud., 1819 Hall, 1916, Helminthoxys urichi (Cameron & Reesal, 1951 Hugot, 1986 and the cestode R. (R. trinitatae represent new host record for Dasyprocta fuliginosa. New morphometric data and remarks about each species are provided.Foram estudadas quatro espécies de nematóides e uma de cestóide coletados de três cutias - duas Dasyprocta fuliginosa Wagler, 1832 e uma Dasyprocta leporina (Linnaeus, 1758 - e seis pacas - Agouti paca (Linnaeus, 1766 - capturadas em rios afluentes na microrregião do médio e alto Rio Negro, Estado do Amazonas, Brasil. Os nematóides Physaloptera torresi (Travassos, 1920 Ortlepp, 1922, Physocephalus mediospiralis (Molin, 1859 Hall, 1916 e o cestóide Raillietina (R. trinitatae (Cameron & Reesal, 1951 Baer & Sandars, 1956 são registrados pela primeira vez no Estado do Amazonas. Os helmintos estudados (os nematóides P. torresi, P. mediospiralis, Trichuris gracilis (Rud., 1819 Hall, 1916, Helminthoxys urichi (Cameron & Reesal, 1951 Hugot, 1986 e o cestóide R. (R. trinitatae representam novos registros para Dasyprocta fuliginosa. Novos dados morfométricos e observações sobre cada espécie são fornecidos.

  8. Genetic Organization of the agouti Region of the Mouse

    OpenAIRE

    Linda D. Siracusa; Russell, Liane B.; Eicher, Eva M; Corrow, Dorcas J.; Neal G Copeland; Jenkins, Nancy A

    1987-01-01

    The agouti locus on mouse chromosome 2 acts via the hair follicle to control the melanic type and distribution of hair pigments. The diverse phenotypes associated with various agouti mutations have led to speculation about the organization of the agouti locus. Earlier studies indicated that two presumed agouti alleles, lethal yellow (Ay) and lethal light-bellied nonagouti (ax), are pseudoallelic. We present genetic data showing probable recombination between Ay and three agouti mutations (...

  9. Modulation of social behavior by the agouti pigmentation gene

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    Valeria eCarola

    2014-08-01

    Full Text Available Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors. Mice and rats lacking agouti (called non-agouti have dark fur due to a disinhibition of melanocortin signaling and pigment deposition in the hair follicle. Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin. Here we confirm that non-agouti mice show altered social behavior and uncover expression of agouti in the preputial gland, a sebaceous organ in the urinary tract that secretes molecules involved in social behavior. Non-agouti mice had enlarged preputial glands and altered levels of putative preputial pheromones and surgical removal of the gland reversed the behavioral phenotype. These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

  10. Genetic organization of the agouti region of the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Siracusa, L.D.; Russell, L.B.; Eicher, E.M.; Corrow, D.J.; Copeland, N.G.; Jenkins, N.A.

    1987-09-01

    The agouti locus on mouse chromosome 2 acts via the hair follicle to control the melanic type and distribution of hair pigments. The diverse phenotypes associated with various agouti mutations have led to speculation about the organization of the agouti locus. Earlier studies indicated that two presumed agouti alleles, lethal yellow (A/sup y/) and lethal light-bellied nonagouti (a/sup x/), are pseudoallelic. The authors present genetic data showing probable recombination between A/sup y/ and three agouti mutations (a/sup t/, a, and a/sup x/), which suggest that A/sup y/ is a pseudoallele of the agouti locus. The close linkage of an endogenous ecotropic murine leukemia provirus, Emv-15, to A/sup y/ provides a molecular access to genes at or near the agouti locus. However, previous studies suggested that the Emv-15 locus can recombine with some agouti alleles and therefore they analyzed mice from recombinant inbred strains and backcrosses to measure the genetic distance between various agouti alleles and the Emv-15 locus. The data indicate that the Emv-15 locus is less the 0.3 cM from the agouti locus. These experiments provide a conceptual framework for initiating chromosome walking experiments designed to retrieve sequences from the agouti locus and give new insight into the genetic organization of the agouti region.

  11. Splenic melanosis in agouti and black mice.

    Science.gov (United States)

    Michalczyk-Wetula, Dominika; Wieczorek, Justyna; Płonka, Przemysław M

    2015-01-01

    An interesting example of extradermal deposition of melanin in vertebrates, notably in mammals, is splenic melanosis. In particular, if the phenomenon of splenic melanosis is correlated with hair or skin pigmentation, it must reflect the amount and perhaps the quality of pigment produced in hair follicle melanocytes. The present paper is our first study on splenic pigmentation in mice of phenotype agouti. We used untreated mixed background mice C57BL/6;129/SvJ (black - a/a, agouti - A/a, A/A), and as a control - black C57BL/6 and agouti fur from 129/SvJ mice, Mongolian gerbils (Meriones unguiculatus) and golden hamsters (Mesocricetus auratus). After euthanasia skin and spleen was evaluated macroscopically, photographed and collected for further analysis using Fontana-Masson and hematoxylin-eosin staining and electron paramagnetic resonance (EPR) at X-band. Spleens of the agouti mice revealed splenic melanosis but were slightly weaker pigmented than their black counterparts, while the presence of pheomelanin was difficult to determine. The fur of both phenotypes was of similar melanin content, with the same tendency as in the spleens. The contribution of pheomelanin in the agouti fur was on the border of detectability by EPR. Histological and EPR analysis confirmed the presence of melanin in the melanotic spleens. The shape of the EPR signal showed a dominance of eumelanin in fur and in melanized spleens in both phenotypes of mice. Therefore, splenic melanosis does reflect the hair follicle pigmentation not only in black, but also in agouti mice. PMID:26291042

  12. INDICADORES HEMATOLÓGICOS Y HEMOQUÍMICOS DE Dasyprocta fuliginosa (GUARA, GUATÍN O ÑEQUE EN CAUTIVERIO

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    Lizcano L.

    2006-11-01

    Full Text Available Los indicadores hematológicos y hemoquímicos de la Dasyprocta fuliginosa (guara, guatín o ñeque en cautiverio se realizaron en el municipio de Florencia, Caquetá (Colombia, pretendiendo iniciar una referencia de datos para estudios de conservación, manejo productivo y clínico de la especie. Fueron utilizados diez animales machos en dos estados de desarrollo (juveniles y adultos. Para hemograma se determinaron hematocrito (técnica de microhematocrito, hemoglobina (método espectrofotométrico de la cianometahemoglobina, recuento total de leucocitos (técnica del hemocitómetro y recuento diferencial de leucocitos (frotis sanguíneo coloreado, y en hemoquímica se determinó glicemia (método GOD-PAP, colesterol (método CHOD-PAP, triglicéridos (método GPO-PAP, proteínas totales (método Biuret y creatinina (método colorimétrico simétrico. Los valores promedios para los parámetros evaluados en hemograma fueron: hematocrito 49,9 ± 2,9%; hemoglobina 16,5 ± 1,1 g/dl; recuento leucocitario total 6650 ± 1276,9 leucocitos/mm3; neutrófilos 17,7 ± 12,9%; linfocitos 77,6 ± 12,4%, y eosinófilos 5,1 ± 3,2 %. Para hemoquímica los resultados fueron: glicemia 249,9 ± 47,1 mg/dl; colesterol 108,1 ± 20,1 mg/dl; triglicéridos 108,1 ± 20,1 mg/dl, proteínas totales 5,7 ± 0,6 g/dl, y creatinina 1,7 ± 0,2 mg/dl. En algunos individuos los valores se desviaron significativamente del promedio, debiéndose tal vez a circunstancias fisiológicas e individuales (estrés, respuesta a mecanismos externos o por lesiones que padecían días antes a la toma de la muestra. Los indicadores del hemograma estuvieron en promedios similares a los de otros roedores del piedemonte amazónico: Proechimys sp., Agouti paca e Hydrochaeris hydrochaeris, al igual que en los hemoquímicos, salvo en glicemia, en donde se encontraron mayores valores para Dasyprocta fuliginosa, debido posiblemente al régimen alimenticio que se basaba sobre todo en frutas y

  13. INTESTINAL MICROBIOTE IN AGOUTIS BRED IN CAPTIVITY MICROBIOTA INTESTINAL EM CUTIAS CRIADAS EM CATIVEIRO

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    LEANDRO LUÍS MARTINS

    2009-07-01

    Full Text Available Intestines are colonized by microorganisms, which vary according to the species and the intestinal region. Thus, due the lack of information about this subject in literature, this research was developed for better knowing some aspects of the intestinal microbiology of the agouti, considered one of the biggest Brazilian wild rodents. Three males and three not pregnant adult females, belonging to the Catanduva City Zoo, SP, went through laparotomy after anesthesia. Samples were collected with sterile swab in the medium thirds of the jejune, cecum and greater colon after enterotomy. They were cultivated in Sabouraud agar and in TSA (triptone-soy agar. In the jejune, the growth of Staphylococcus aureus and Escherichia coli was of 83.33%, Salmonella spp. of 66.67% and Clostridium spp. of 50.00% of the samples. In the cecum, they were identified Staphylococcus aureus in 33.33%, Escherichia coli, Salmonella spp. and Clostridium spp. in 100% and Streptococcus spp. in 16.67% of the samples were identified. In the greater colon, the growth of Salmonella spp., Escherichia coli and Clostridium spp. in 66.67%, Staphylococcus aureus in 83.33%, and Streptococcus spp. in 16.67% of the samples was observed, showing the occurrence of variations in the bacteriae proportion according to the intestinal region. 

    KEY WORDS: Dasyprocta azarae, intestines, microbiote.

    Os intestinos são colonizados por microorganismos, variáveis de acordo com a espécie e região intestinal. Assim, em virtude da ausência de informações sobre esse assunto na literatura, esta pesquisa foi desenvolvida para melhor se conhecer alguns aspectos da microbiota intestinal da cutia, um dos maiores roedores selvagens brasileiros. Três machos e três fêmeas adultas vazias, pertencentes ao Zoológico Municipal de Catanduva, SP, foram submetidos a laparotomia mediante anestesia. Amostras com swab estéril foram coletadas nos terços médios do jejuno, ceco e c

  14. DESCRIÇÃO HISTOLÓGICA DOS INCISIVOS DA CUTIA Dasyprocta prymnolopha (Wagler, 1831)

    OpenAIRE

    Weber Leal de Moura; Adriana Maria Viana Nunes Pinheiro; Débora Cavalcante Braz; Maria Acelina de Carvalho

    2006-01-01

    Esse trabalho objetivou descrever a histologia do dente e do periodonto de cutia. Utilizaram-se dez exemplares de Dasyprocta prymnolopha, desconsiderando idade e sexo. Realizado o processamento histológico clássico, o esmalte e o cemento desintegraram-se na descalcificação, evidenciando-se que o cemento apresenta uma quantidade de tecido mineralizado maior que a dentina. Na dentina, observaram-se túbulos dentinários, estriações paralelas, flexíveis, sinuosas e perpendiculares ao eixo maior do...

  15. Analysis of the function of the agouti gene in obesity and diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Mynatt, R.L.; Miltenberger, R.J.; Klebig, M.L. [and others

    1996-09-01

    This chapter discusses the agouti gene and dominant mutations in that gene that lead to agouti-induced obesity, and recent work with transgenic mice to elucidate the role of agouti in obesity. Agouti was cloned in 1992 by the lab of Rick Woychik at Oak Ridge National Laboratory, making it the first of many recently cloned mouse obesity genes. Sequence analysis predicted that mouse agouti is a secreted protein of 131 amino acids. The mature protein has a basic central region (lys57-arg85), a proline-rich domain (pro86-pro91) and a C-terminal region (cys 92-cys 13 1) containing 10 cysteine residues which form 5 disulfide bonds. The human homologue of agouti has also been cloned by the Woychik lab and maps to human chromosome 20q 11.2. Human agouti is 132 amino acids long and is 85% similar to the mouse agouti protein and is normally expressed in adipose tissue. The researchers have been able to recapitulate obesity, hyperinsulinemia, and hyperglycemia with the ubiquitous expression of agouti. Agouti expression in either liver and adipose tissue alone does not cause obesity, and there`s a dose-dependent effect of agouti on body weight, food efficiency, body temperature, and insulin and glucose levels.

  16. DESCRIÇÃO HISTOLÓGICA DOS INCISIVOS DA CUTIA Dasyprocta prymnolopha (Wagler, 1831

    Directory of Open Access Journals (Sweden)

    Weber Leal de Moura

    2006-10-01

    Full Text Available Esse trabalho objetivou descrever a histologia do dente e do periodonto de cutia. Utilizaram-se dez exemplares de Dasyprocta prymnolopha, desconsiderando idade e sexo. Realizado o processamento histológico clássico, o esmalte e o cemento desintegraram-se na descalcificação, evidenciando-se que o cemento apresenta uma quantidade de tecido mineralizado maior que a dentina. Na dentina, observaram-se túbulos dentinários, estriações paralelas, flexíveis, sinuosas e perpendiculares ao eixo maior do dente, presentes em maior quantidade na região próxima à pré-dentina. A dentina foi classificada em peritubular, intertubular e interglobular, além da pré-dentina, delgada porção não mineralizada. Os odontoblastos mostraram-se acidófilos, paralelos, dispostos ‘’em paliçada’’, ocupando o espaço entre a dentina e a polpa. A polpa apresentou tecido conjuntivo frouxo bastante vascularizado e inervado, cujas células predominantes foram fibroblastos de aspecto estrelado e fusiforme com longos prolongamentos citoplasmáticos. O periodonto mostrou cemento, ligamento periodontal e osso alveolar. O ligamento foi classificado em inferior (conjuntivo denso e superior (conjuntivo frouxo com o primeiro apresentando áreas globulares provenientes da comunicação do osso alveolar e o segundo um epitélio juncional pseudo-estratificado. As fibras de Sharpey partiam do ligamento, inserindo-se no osso alveolar,cujas lamelas formariam delgadas trabéculas e de osso compacto formado pelos sistemas de Havers. PALAVRAS-CHAVE: Dente, dentino-pulpar, Dasyprocta periodonto.

  17. Induction of brain region-specific forms of obesity by agouti.

    OpenAIRE

    Kas, M. J. H.; Tiesjema, B; Dijk, G. van; Garner, KM; Barsh, GS; ter Brake, O; Verhaagen, J.; Adan, RAH

    2004-01-01

    Disruption of melanocortin ( MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti expression was induced after local injections of recombinant adeno-associated viral particles in selected brain nuclei of adult rats. Agouti expression in the paraventricular nucleus, a hypothalamic reg...

  18. Isolation and characterization of Agouti: a diabetes/obesity related gene

    Science.gov (United States)

    Woychik, Richard P.

    1998-01-01

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  19. Isolation and characterization of Agouti: a diabetes/obesity related gene

    Energy Technology Data Exchange (ETDEWEB)

    Woychik, Richard P. (Knoxville, TN)

    2000-06-27

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  20. Experimental heteroxenous cycle of Lagochilascaris minor Leiper, 1909 (Nematoda: Ascarididae in white mice and in cats

    Directory of Open Access Journals (Sweden)

    Gregorio S. Volcan

    1992-12-01

    Full Text Available Reports of natural infections of sylvatic carnivores by adult worms of species similar to Lagochilascaris minor in the Neotropical region led to attempts to estabilish experimental cycles in laboratory mice and in cats. Also, larval development was seen in the skeletal muscle of an agouti (Dasyprocta leporina infected per os with incubated eggs of the parasite obtained from a human case. In cats, adult worms develop and fertile eggs are expelled in the feces: in mice, larval stages of the parasite develop, and are encapsulate in the skeletal muscle, and in the adipose and subcutaneous connective tissue. From our observations, we conclude that the larva infective for the mouse is the early 3rd stage, while for the final host the infective form is the later 3rd stage. A single moult was seen in the mouse, giving rise to a small population of 4th stage larvae, long after the initial infection.

  1. Induction of brain region-specific forms of obesity by Agouti

    NARCIS (Netherlands)

    Kas, M.J.H.; Tiesjema, B; van Dijk, G; Garner, KM; Barsh, GS; Ter Brake, O; Verhaagen, J; Adan, RAH

    2004-01-01

    Disruption of melanocortin ( MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti expre

  2. Induction of brain-region-specific forms of obesity by agouti

    NARCIS (Netherlands)

    Kas, Martien J H; Tiesjema, Birgitte; van Dijk, Gertjan; Garner, Keith M; Barsh, Gregory S; ter Brake, Olivier; Verhaagen, Joost; Adan, Roger A H

    2004-01-01

    Disruption of melanocortin (MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti expres

  3. Molecular analysis of the mouse agouti gene and the role of dominant agouti-locus mutations in obesity and insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Klebig, M.L.; Woychik, R.P. [Oak Ridge National Lab., TN (United States); Wilkinson, J.E. [Univ. of Tennessee, Knoxville, TN (United States)

    1994-09-01

    The lethal yellow (A{sup y/-}) and viable yellow (A{sup vy/-}) mouse agouti mutants have a predominantly yellow pelage and display a complex syndrome that includes obesity, hyperinsulinemia, and insulin resistance, hallmark features of obesity-associated noninsulin-dependent diabetes mellitus (NIDDM) in humans. A new dominant agouti allele, A{sup iapy}, has recently been identified; like the A{sup vy} allele, it is homozygous viable and confers obesity and yellow fur in heterozygotes. The agouti gene was cloned and characterized at the molecular level. The gene is expressed in the skin during hair growth and is predicted to encode a 131 amino acid protein, that is likely to be a secreted factor. In both Ay/- and A{sup iapy}/- mice, the obesity and other dominant pleiotropic effects are associated with an ectopic expression of agouti in many tissues where the gene product is normally not produced. In Ay, a 170-kb deletion has occurred that causes an upstream promoter to drive the ectopic expression of the wild-type agouti coding exons. In A{sup iapy}, the coding region of the gene is expressed from a cryptic promoter within the LTR of an intracisternal A-particle (IAP), which has integrated within the region just upstream of the first agouti coding exon. Transgenic mice ubiquitously expressing the cloned agouti gene under the influence of the beta-actin and phosphoglycerate kinase promoters display obesity, hyperinsulinemia, and yellow coat color. This demonstrates unequivocally that ectopic expression of agouti is responsible for the yellow obese syndrome.

  4. Cariotipo Citogenético de la Guagua (agouti paca

    Directory of Open Access Journals (Sweden)

    López Ortiz Juan Bautista

    1997-12-01

    Full Text Available El presente trabajo reporta la dotación cromosómica de Agouti paca, una especie considerada en vía de extinción. Además, se muestra la estandarización de la técnica para la obtención de cromosomas en sangre periférica y el tiempo óptimo del pulso terminal de 5-bromo-2 'deoxiuridina (BrdUrd para la obtención de bandas R-replicativas de alta resolución. También, se compara el cariotipo obtenido usando tinción convencional de Giemsa, con el realizado utilizando bandeo replicativo de alta resolución. El análisis de la morfología cromosómica del cariotipo de Agouti paca, muestra 29 pares de cromosomas subtelocéntricos, 2 cromosomas acrocéntricos y 5 pares cromosómicos metacéntricos. De todo el cariotipo, el cromosoma X es el más grande y lo clasificamos como: submetacéntrico. El cromosoma Y es el más pequeño y lo consideramos acrocéntrico. Además, al igual que en todas las hembras de mamíferos, la hembra de guagua exhibe un cromosoma X inactivo de replicación tardía. Con base en los resultados obtenidos, se determina el número cromosómico 2n = 74. De acuerdo con la ISCI (1995, propusimos una clasificación en 5 grupos: grupo A del 1 al 10, grupo B del 11 al 20, grupo C del 21 al 29, grupo D del 30 al 31 y grupo E del 32 al 36, además del parsexual (XX si es hembra, XY si es macho. Estos hallazgos posibilitarán en el futuro, establecer la correlación entre anormalidades cromosómicas y cambios fenotípicos o trastornos reproductivos de la especie; además, servirá como parámetro citogenético en la comparación de Agouti paca con otros Hystricomorfos relacionados. Este resultado se constituye en el primer cariotipo de Agouti paca (guagua, reportado; además, es el primer estudio citogenético donde se realizan bandas R-replicativas de alta resolución para cariotipar especies animales promisorias

  5. [Ovarian activity of Agouti paca (Rodentia: Agoutidae) under captivity].

    Science.gov (United States)

    Montes Pérez, Rubén C; Cabrera Baz, Elsy A

    2006-09-01

    The ovarian activity of Agouti paca was characterized by hormonal profiles and ovarian structures. Samples of blood were taken from eight females (seven adults and one juvenile) at the breeding grounds of the Facultad de Medicina Veterinaria y Zootecnia in Yucatśn, Mexico. Sampling lasted approximately two months and was done every three and six days. Blood was collected from anesthetized animals, and the levels of progesterone (P4) and 17 beta estradiol (E2) were analized by radioimmunoassay technique. Macroscopic and microscopic analyses were carried out in ovaries of dead animals. The estrous cycle lasted 29+/-8.4 days, levels of 1.61+/-0.65 ng/ml for P4 and 39+/-24 pg/ml for E2 were observed for a follicular phase, 6.18+/-3.70 ng/ml and 29+/-16 pg/ml for P4 and E2 respectively in the luteal phase. Statistically significant differences were found between phases for P4 but not for E2. The presence of extragonadal steroids with levels of P4 of 1.9+/-0.77 ng/ml and E2 of 22+/-17 pg/ml were observed, which are not produced by the effects of managing stress. The changes in the levels of P4 during the cycle are indicators of luteal activity, with the intersticial tissue acting probably as active steroids-producing gland. Follicular growth was observed during the entire cycle.

  6. The effects of calcium channel blockade on agouti-induced obesity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Han; Moustaid, N.; Zemel, M.B. [Univ. of Tennessee, Knoxville, TN (United States)] [and others

    1996-12-01

    We have previously observed that obese viable yellow (A{sup vy}/a) mice exhibit increased intracellular Ca{sup 2+} ([Ca{sup 2+}]i) and fatty acid synthase (FAS) gene expression; further, recombinant agouti protein increases in cultured adipocytes and these effects are inhibited by Ca{sup 2+} channel blockade. Accordingly, we determined the effect of Ca{sup 2+} channel blockade (nifedipine for 4 wk) on FAS and obesity in transgenic mice expressing the agouti gene in a ubiquitous manner. The transgenic mice initially were significantly heavier (30.5 {+-} 0.6 vs. 27.3 {+-} 0.3 g; P<0.001) and exhibited a 0.81{degrees}C lower initial core temperature (P<0.0005), an approximately twofold increase in fat pad weights (P=0.002), a sevenfold increase in adipose FAS activity (P=0.009), and a twofold increase in plasma insulin level (P<0.05) compared to control mice. Nifedipine treatment resulted in an 18% decrease in fat pad weights (P<0.007) and a 74% decrease in adipose FAS activity (P=0.03), normalized circulating insulin levels and insulin sensitivity (P,0.05), and transiently elevated core temperature in the transgenic mice, but was without effect in the control mice. These data suggest that agouti regulates FAS, fat storage, and possibly thermogenesis, at least partially, via a [Ca{sup 2+}]{sub i}-dependent mechanism, and that Ca{sup 2+} channel blockade may partially attenuate agouti-induced obesity. 42 refs., 4 figs., 1 tab.

  7. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur

    Energy Technology Data Exchange (ETDEWEB)

    Klebig, M.L.; Woychik, R.P. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Wilkinson, J.E. [Univ. of Tennessee, Knoxville, TN (United States); Geisler, J.G. [Oak Ridge National Laboratory, Oak Ridge, TN (United States)]|[Univ. of Tennessee, Knoxville, TN (United States)

    1995-05-23

    Mice that carry the lethal yellow (A{sup y}) or viable yellow (A{sup vy}) mutation, two dominant mutations of the agouti (a) gene in mouse chromosome 2, exhibit a phenotype that includes yellow fur, marked obesity, a form of type II diabetes associated with insulin resistance, and an increased susceptibility to tumor development. Molecular analyses of these and several other dominant {open_quotes}obese yellow{close_quotes} a-locus mutations suggested that ectopic expression of the normal agouti protein gives rise to this complex pleiotropic phenotype. We have now tested this hypothesis directly by generating transgenic mice that ectopically express an agouti cDNA clone encoding the normal agouti protein in all tissues examined. Transgenic mice of both sexes have yellow fur, become obese, and develop hyperinsulinemia. In addition, male transgenic mice develop hyperglycemia by 12-20 weeks of age. These results demonstrate conclusively that the ectopic agouti expression is responsible for most, if not all, of the phenotypic traits of the dominant, obese yellow mutants. 42 refs., 5 figs.

  8. Molecular basis of the pleiotropic phenotype of mice carrying the hypervariable yellow (A{sup hvy}) mutation at the agouti locus

    Energy Technology Data Exchange (ETDEWEB)

    Argeson, A.C.; Nelson, K.K.; Siracusa, L.D. [Jefferson Cancer Center, Philadelphia, PA (United States)

    1996-02-01

    The murine agouti locus regulates a switch in pigment synthesis between eumelanin (black/brown pigment) and phaeomelanin (yellow/red pigment) by hair bulb melanocytes. We recently described a spontaneous mutation, hypervariable yellow (A{sup hvy}) and demonstrated that A{sup hvy} is responsible for the largest range of phenotypes yet identified at the agouti locus, producing mice that are obese with yellow coats to mice that are of normal weight with black coats. Here, we show that agouti expression is altered both temporally and spatially in A{sup hvy} mutants. Agouti expression levels are positively correlated with the degree of yellow pigmentation in individual A{sup hvy} mice, consistent with results from other dominant yellow agouti mutations. Sequencing of 5{prime} RACE and genomic PCR products revealed that A{sup hvy} resulted from the integration of an intracisternal A particle (IAP) in an antisense orientation within the 5{prime} untranslated agouti exon 1C. This retrovirus-like element is responsible for deregulating agouti expression in A{sup hvy} mice; agouti expression is correlated with the methylation state of CpG residues in the IAP long terminal repeat as well as in host genomic DNA. In addition, the data suggest that the variable phenotype of A{sup hvy} offspring is influenced in part by the phenotype of their A{sup hvy} female parent. 42 refs., 7 figs., 1 tab.

  9. Características reprodutivas da paca fêmea (Agouti paca criada em cativeiro Reprodutive characteristics of the female paca (Agouti paca raised in captivity

    Directory of Open Access Journals (Sweden)

    Diva Anelie de Araújo Guimarães

    2008-01-01

    Full Text Available O objetivo do trabalho foi estudar a biologia reprodutiva da Agouti paca criada em cativeiro. Os resultados demonstraram que, a duração média do ciclo estral foi de 32,5 + 3,7 dias e o período gestacional de 148,6 + 4,8 dias. O intervalo entre partos foi de 224,5 + 52,2 dias e o primeiro cio pós-parto foi de 25,6 + 8,8 dias. A maioria (55,6 % das fêmeas apresentou dois partos por ano, com o nascimento de um filhote por parto, sendo 44,7 % fêmeas e 55,3 % machos. Ao nascer o peso médio das fêmeas foi de 605,9 + 87,5 g e dos machos 736,7 + 108,4 g (P The objective of this paper was to study the reproductive biology of the Agouti paca raised in captivity. It was observed that the estrous cycle average was 32.5 + 3.7 days, gestation length 148.6 + 4.8 days, parturition interval 224.5 + 52.2 days, and the first post-partum 25.6 + 8.8 days. It was also observed that 55.5% of the females presented two parturitions per year with one young per parturition, of which 44.7% were females and 55.3% were males. The birth weight was 605.9 + 87.8 g for females and 736.7 + 108.4 g for males (P<0.05. Puberty in females occurred between 8 to 12 months; for this, however, more detailed investigations are necessary.

  10. Teriflunomide attenuates immunopathological changes in the Dark Agouti rat model of experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Garth E. Ringheim

    2013-10-01

    Full Text Available Teriflunomide is an oral disease-modifying therapy recently approved in several locations for relapsing forms of multiple sclerosis. To gain insight into the effects of teriflunomide, immunocyte population changes were measured during progression of experimental autoimmune encephalomyelitis in Dark Agouti rats. Treatment with teriflunomide attenuated levels of spinal cord-infiltrating T cells, natural killer cells, macrophages, and neutrophils. Teriflunomide also mitigated the disease-induced changes in immune cell populations in the blood and spleen suggesting an inhibitory effect on pathogenic immune responses.

  11. Recombinant Inbred Strain and Interspecific Backcross Analysis of Molecular Markers Flanking the Murine Agouti Coat Color Locus

    OpenAIRE

    Siracusa, L. D.; Buchberg, A M; Copeland, N. G.; Jenkins, N.A.

    1989-01-01

    Recombinant inbred strain and interspecific backcross mice were used to create a molecular genetic linkage map of the distal portion of mouse chromosome 2. The orientation and distance of the Ada, Emv-13, Emv-15, Hck-1, Il-1a, Pck-1, Psp, Src-1 and Svp-1 loci from the β(2)-microglobulin locus and the agouti locus were established. Our mapping results have provided the identification of molecular markers both proximal and distal to the agouti locus. The recombinants obtained provide valuable r...

  12. An obesity-dependent lactation defect in the viable yellow agouti mouse is associated with mammary inflammation

    Science.gov (United States)

    Maternal obesity is known to delay lactogenesis in breast-feeding women, as well as negatively impact lactation in other species. Obesity is also understood to be associated with inflammation. Work with the viable yellow agouti (Avy) mouse in our laboratory has documented a lactation defect in obese...

  13. Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kuklin, Alexander [ORNL; Mynatt, Randall [ORNL; Klebig, Mitch [ORNL; Kiefer, Laura [Glaxo Wellcome, Research Triangle Park, NC; Wilkison, William O [Glaxo Wellcome, Research Triangle Park, NC; Woychik, Richard P [Jackson Laboratory, The, Bar Harbor, ME; Michaud III, Edward J [ORNL

    2004-01-01

    Background: The agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r) on melanocytes. Lethal yellow (Ay) and viable yellow (Avy) are dominant regulatory mutations in the mouse agouti gene that cause the wild- ype protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis in numerous tissues, including the liver. The goal of this research was to determine if ectopic expression of the agouti gene in the liver alone is sufficient to recapitulate any aspect of this syndrome. For this purpose, we generated lines of transgenic mice expressing high levels of agouti in the liver under the regulatory control of the albumin promoter. Expression levels of the agouti transgene in the liver were quantified by Northern blot analysis. Functional agouti protein in the liver of transgenic mice was assayed by its ability to inhibit binding of the -melanocyte stimulating hormone ( MSH) to the Mc1r. Body weight, plasma insulin and blood glucose levels were analyzed in control and transgenic mice. Control and transgenic male mice were given a single intraperitoneal injection (10 mg/kg) of the hepatocellular carcinogen, diethylnitrosamine (DEN), at 15 days of age. Mice were euthanized at 36 or 40 weeks after DEN injection and the number of tumors per liver and total liver weights were recorded. Results: The albumin-agouti transgene was expressed at high levels in the livers of mice and produced a functional agouti protein. Albumin-agouti transgenic mice had normal body weights and normal levels of blood glucose and plasma insulin, but responded to chemical initiation of the liver with an increased number

  14. Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

    Directory of Open Access Journals (Sweden)

    Kiefer Laura L

    2004-06-01

    Full Text Available Abstract Background The agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r on melanocytes. Lethal yellow (Ay and viable yellow (Avy are dominant regulatory mutations in the mouse agouti gene that cause the wild-type protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis in numerous tissues, including the liver. The goal of this research was to determine if ectopic expression of the agouti gene in the liver alone is sufficient to recapitulate any aspect of this syndrome. For this purpose, we generated lines of transgenic mice expressing high levels of agouti in the liver under the regulatory control of the albumin promoter. Expression levels of the agouti transgene in the liver were quantified by Northern blot analysis. Functional agouti protein in the liver of transgenic mice was assayed by its ability to inhibit binding of the α-melanocyte stimulating hormone (αMSH to the Mc1r. Body weight, plasma insulin and blood glucose levels were analyzed in control and transgenic mice. Control and transgenic male mice were given a single intraperitoneal injection (10 mg/kg of the hepatocellular carcinogen, diethylnitrosamine (DEN, at 15 days of age. Mice were euthanized at 36 or 40 weeks after DEN injection and the number of tumors per liver and total liver weights were recorded. Results The albumin-agouti transgene was expressed at high levels in the livers of mice and produced a functional agouti protein. Albumin-agouti transgenic mice had normal body weights and normal levels of blood glucose and plasma insulin, but responded to chemical initiation of the liver

  15. Agouti and Agouti-related Proteins%Agouti和Agouti相关蛋白的一些生物学内涵

    Institute of Scientific and Technical Information of China (English)

    杨云青; 高丹玫; 郭宗圣

    2008-01-01

    Agouti 有多方面的意义.首先,它是分属几种不同物种的哺乳动物的俗称.其次,它是一些啮齿类动物的属名.第三,它代表了一种啮齿类动物特有的毛色.第四,它是一个与黑素皮质素受体信号转导途径的调控有关,存在于从人(Homo sapiens)到啮齿类动物,乃至斑马鱼(Danio rerio)的一个特定基因的名称,又是该基因产生的一种特定信号蛋白的名称.Agouti和Agouti相关蛋白是肿瘤、肥胖与糖尿病等人类疾病的研究热点之一.Agouti黄色肥胖小鼠最近成了表观遗传学研究的一个重要模型动物.本文阐述并区分了与agouti有关的一些重要概念与科学术语,并综述了相关领域的研究进展.

  16. Dark Agouti rat model of chemotherapy-induced mucositis: establishment and current state of the art.

    Science.gov (United States)

    Vanhoecke, Barbara; Bateman, Emma; Mayo, Bronwen; Vanlancker, Eline; Stringer, Andrea; Thorpe, Daniel; Keefe, Dorothy

    2015-06-01

    Mucositis is a major oncological problem. The entire gastrointestinal and genitourinary tract and also other mucosal surfaces can be affected in recipients of radiotherapy, and/or chemotherapy. Major progress has been made in recent years in understanding the mechanisms of oral and small intestinal mucositis, which appears to be more prominent than colonic damage. This progress is largely due to the development of representative laboratory animal models of mucositis. This review focuses on the development and establishment of the Dark Agouti rat mammary adenocarcinoma model by the Mucositis Research Group of the University of Adelaide over the past 20 years to characterize the mechanisms underlying methotrexate-, 5-fluorouracil-, and irinotecan-induced mucositis. It also aims to summarize the results from studies using different animal model systems to identify new molecular and cellular markers of mucositis.

  17. BIOMETRY OF PACA NEWBORNS BRED IN CAPTIVITY(AGOUTI PACA, LINNAEUS, 1766 NOTA CIENTÍFICA: BIOMETRIA DOS NEONATOS DE PACA CRIADOS EM CATIVEIRO (AGOUTI PACA, LINNAEUS, 1766

    Directory of Open Access Journals (Sweden)

    Júlio Carlos Canola

    2007-12-01

    Full Text Available

    Biometry provides important data on weight and length of wild animal newborns. After ultrasound pregnancy detection, 22 female pacas were separated in individual bails and kept until weaning of newborns. Newborns were measured with a metric tape (between the tips of the muzzle rostrally and the tail distally and weighted in a digital weight scale. Considering males and females, the average newborn length (average length ± standard deviation was 33.37 ± 0.57cm. Among males, the average weight was 33.30 ± 0.52 cm and among females 33.45 ± 0.62cm. Considering males and females, newborns weighted (average weight ± standard deviation 741.14 ± 51.23g. Among males, average weight was 717.75 ± 49.06g and among females 764.53 ± 53.40g. Female newborns are higher and heavier than males, but averages of weight and length of males and females did not differ themselves by the Tukey test (P<0.05.

    Key-words: Agouti paca, biometry, newborns.

    A biometria proporciona dados importantes no peso e comprimento de neonatos de animais selvagens. Após detecção ultra-sonográfica da prenhez, 22 pacas fêmeas foram separadas em baias individuais e mantidas até o desmame dos filhotes. Os neonatos eram medidos com uma fita métrica flexível (entre as extremidades do focinho e da caudal e então pesados em balança digital de precisão. Considerando-se machos e fêmeas, o comprimento dos neonatos (comprimento ± desvio padrão foi 33,37 ± 0,57 cm. Entre os machos, o comprimento médio foi 33,30 ± 0,52 cm e entre as fêmeas foi de 33,45 ± 0,62 cm. Em relação ao peso e considerando-se machos e fêmeas, os neonatos pesavam (peso ± desvio padrão 741,14 ± 51,23g. Entre os machos, o peso médio foi 717,75 ± 49,06g e entre as fêmeas 764,53 ± 53,40g. Os neonatos fêmeas são maiores e mais pesados que os neonatos machos de paca, mas as médias de peso e de comprimento de machos e fêmeas n

  18. Erupção dental em pacas (Agouti paca criadas em cativeiro Dental eruption in pacas (Agouti paca bred in captivity

    Directory of Open Access Journals (Sweden)

    F.S. Oliveira

    2007-04-01

    Full Text Available Fez-se o acompanhamento radiográfico mensal da erupção dental de cinco fêmeas e sete machos da espécie Agouti paca durante 30 meses. Os animais foram radiografados mês-a-mês. As pacas nasceram com três dentes em cada hemiarcada dental, um incisivo de crescimento contínuo por toda a vida, um pré-molar decíduo (o único que é decíduo e um molar. No quarto mês houve a erupção do segundo molar. O nivelamento da superfície de oclusão dos dentes inferiores ocorreu no sexto mês e o dos superiores ao redor do nono mês. No 14° mês, houve o início da erupção do terceiro molar e, no 16° mês, a evidenciação radiográfica do pré-molar permanente, ainda com preservação de correspondente decíduo. No 21° mês, ocorreu o nivelamento da superfície de oclusão dos quatro dentes superiores e inferiores. Entre o 22° e o 24° mês, iniciou-se a queda dos pré-molares decíduos inferiores e, entre o 23º e o 24° mês, a dos superiores. Entre o 24º e o 25º mês, a superfície de oclusão dos dentes inferiores estava nivelada, e a dos dentes superiores aconteceu no 27º mês.Five females and seven males of Agouti paca were used to study dental eruption. In a monthly radiographic survey of the dental eruption, during 30 consecutive months, animals were radiographed. Pacas were born with three teeth in each dental hemiarcade, one incisor of continuous growth, one premolar (the only one deciduous and one molar. The second molar erupted in the fourth month. The occlusal surfaces of lower teeth were at the same level in the sixth month and the upper teeth around ninth month. The beginning of the third molar eruption occurred in the 14th month. Perception of the first permanent premolar was around the 16th month, and its correspondent deciduous was still retained. The occlusal surfaces of upper and lower teeth were at the same level in the 21st month. The eruption of the first lower deciduous premolar occurred between the 22nd and 24th

  19. Recovery and cryopreservation of epididymal sperm from agouti (Dasiprocta aguti) using powdered coconut water (ACP-109c) and Tris extenders.

    Science.gov (United States)

    Silva, M A; Peixoto, G C X; Santos, E A A; Castelo, T S; Oliveira, M F; Silva, A R

    2011-10-01

    The objective was to compare the use of powdered coconut water (ACP-109c; ACP Biotecnologia, Fortaleza, CE, Brazil) and Tris extenders for recovery and cryopreservation of epididymal sperm from agouti. The caudae epididymus and proximal ductus deferens from 10 sexually mature agoutis were subjected to retrograde washing using ACP-109c (ACP Biotecnologia) or Tris. Epididymal sperm were evaluated for motility, vigor, sperm viability, membrane integrity, and morphology. Samples were centrifuged, and extended in the same diluents plus egg yolk (20%) and glycerol (6%), frozen in liquid nitrogen, and subsequently thawed at 37°C for 1 min, followed by re-evaluation of sperm characteristics. The two extenders were similarly efficient for epididymal recovery, with regard to the number and quality of sperm recovered. However, for both extenders, sperm quality decreased (P Biotecnologia) group, which was significantly better than 9.7 ± 2.6% motile sperm with 1.2 ± 0.3 vigor in Tris. In conclusion, agouti epididymal sperm were successfully recovered using either ACP-109c (ACP Biotecnologia) or Tris extenders; however, ACP-109c (ACP Biotecnologia) was a significantly better extender for processing and cryopreserving these sperm.

  20. Agouti signalling protein (ASIP) gene: molecular cloning, sequence characterisation and tissue distribution in domestic goose.

    Science.gov (United States)

    Zhang, J; Wang, C; Liu, Y; Liu, J; Wang, H Y; Liu, A F; He, D Q

    2016-06-01

    Agouti signalling protein (ASIP) is an endogenous antagonist of melanocortin-1 receptor (MC1R) and is involved in the regulation of pigmentation in mammals. The objective of this study was to identify and characterise the ASIP gene in domestic goose. The goose ASIP cDNA consisted of a 44-nucleotide 5'-terminal untranslated region (UTR), a 390-nucleotide open-reading frame (ORF) and a 45-nucleotide 3'-UTR. The length of goose ASIP genomic DNA was 6176 bp, including three coding exons and two introns. Bioinformatic analysis indicated that the ORF encodes a protein of 130 amino-acid residues with a molecular weight of 14.88 kDa and an isoelectric point of 9.73. Multiple sequence alignments and phylogenetic analysis showed that the amino-acid sequence of ASIP was conserved in vertebrates, especially in the avian species. RT-qPCR showed that the goose ASIP mRNA was differentially expressed in the pigment deposition tissues, including eye, foot, feather follicle, skin of the back, as well as in skin of the abdomen. The expression level of the ASIP gene in skin of the abdomen was higher than that in skin of the back. Those findings will contribute to further understanding the functions of the ASIP gene in geese plumage colouring. PMID:26750999

  1. Transient ectopic overexpression of agouti-signalling protein 1 (asip1 induces pigment anomalies in flatfish.

    Directory of Open Access Journals (Sweden)

    Raúl Guillot

    Full Text Available While flatfish in the wild exhibit a pronounced countershading of the dorso-ventral pigment pattern, malpigmentation is commonly observed in reared animals. In fish, the dorso-ventral pigment polarity is achieved because a melanization inhibition factor (MIF inhibits melanoblast differentiation and encourages iridophore proliferation in the ventrum. A previous work of our group suggested that asip1 is the uncharacterized MIF concerned. In order to further support this hypothesis, we have characterized asip1 mRNAs in both turbot and sole and used deduced peptide alignments to analyze the evolutionary history of the agouti-family of peptides. The putative asip precursors have the characteristics of a secreted protein, displaying a putative hydrophobic signal. Processing of the potential signal peptide produces mature proteins that include an N-terminal region, a basic central domain with a high proportion of lysine residues as well as a proline-rich region that immediately precedes the C-terminal poly-cysteine domain. The expression of asip1 mRNA in the ventral area was significantly higher than in the dorsal region. Similarly, the expression of asip1 within the unpigmented patches in the dorsal skin of pseudoalbino fish was higher than in the pigmented dorsal regions but similar to those levels observed in the ventral skin. In addition, the injection/electroporation of asip1 capped mRNA in both species induced long term dorsal skin paling, suggesting the inhibition of the melanogenic pathways. The data suggest that fish asip1 is involved in the dorsal-ventral pigment patterning in adult fish, where it induces the regulatory asymmetry involved in precursor differentiation into mature chromatophore. Adult dorsal pseudoalbinism seems to be the consequence of the expression of normal developmental pathways in an inaccurate position that results in unbalanced asip1 production levels. This, in turn, generates a ventral-like differentiation environment

  2. Atributos de qualidade da carne de paca (Agouti paca: perfil sensorial e força de cisalhamento Quality attributes of paca meat (Agouti paca: sensory profile and shear force

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    C. Gomes

    2013-04-01

    Full Text Available Avaliaram-se as características sensoriais e determinou-se a força de cisalhamento de cortes de carne de paca (Agouti paca. As análises foram realizadas nos cortes desossados de paleta, lombo e pernil de nove pacas, preparados por cocção até a temperatura interna de 70ºC. A avaliação de aspecto, cor, sabor, odor e maciez foi realizada pela aplicação de teste afetivo a 146 provadores, utilizando-se escala hedônica, e a força de cisalhamento foi determinada pela técnica Warner Bratzler. Na avaliação sensorial, os cortes de paleta, lombo e pernil de paca mostraram diferença significativa (p0,05 entre os cortes, que se mostraram igualmente macios. A carne de paca apresentou-se sensorialmente semelhante à carne suína e com boa aceitação pelos consumidores. O estudo evidenciou o potencial da paca como uma espécie silvestre para a produção comercial de carne para o mercado de carnes vermelhas ou exóticas.Sensory characteristics and shear force of paca meat (Agouti paca were assessed in this study. Analyses were performed in the bonelessshoulder,loin andhamobtained from nine paca carcassesprepared by cookinguntil reaching the internal temperatureof 70°C. The evaluation of flavor, aroma, color, appearance and tenderness was carried out by the application of an affective test using the hedonic scaleand a 146 consumer panel. Shear force was determined by the Warner-Bratzler technique. Shoulder, loin and ham had significant differences (p 0.05 among the cuts, which were similarly tender. Paca meat was found to resemble pork meat in sensory evaluation and had good acceptance by consumers. This study showed the potential of paca (Agouti paca asa wild species for meat production in the red or exotic meat market.

  3. VALOR AGREGADO DE LAS ESPECIES Brycon erythropterum (SÁBALO, Colossoma macropomum (GAMITANA, Arapaima gigas (PAICHE y Agouti paca (MAJAS

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    Doylith Vásquez Jurafo

    2012-12-01

    Full Text Available El presente trabajo tiene como objetivo  la obtención de  productos mínimamente procesados (PMP de Brycon erythropterum (SÁBALO, Colossoma macropomum (GAMITANA, Arapaima gigas (PAICHE, y Agouti paca (MAJAS congelado y empacado al vacio. Para las especies piscícolas, se ha aplicado un diseño factorial de 32 con dos factores de estudios: concentración de NaCl en la solución osmótica con tres niveles (15, 20 y 25 % y temperatura de proceso  con tres niveles de estudio (5, 10 y 15 °C. Para el Agouti paca (majas se aplico un diseño factorial completamente aleatorizado con tres factores de estudio: tiempo de proceso (30, 60 y 90 minutos, método de ahumado (ahumado líquido y ahumado en caliente y tipo de corte del músculo (partes y filetes. Para trabajar se ha diseñado y montado un deshidratador Osmótico teniendo en cuenta, diámetro de tubería, deshidratador propiamente dicho con doble chaqueta, capacidad del deshidratador en función del volumen de la Salmuera.  Todos los productos se obtuvieron  en procesos con 10 °C y tiempos entre 30 min y  90 min. El tiempo de vida en almacenamiento en las evaluaciones de aroma y color en majas tienen una vida útil de 4 meses de almacenados a -18 °C. Los análisis microbiológicos realizados a los PMP no pasan los límites de la NTS Nº 071 MINSA/DIGESA V01.

  4. 藏羊刺鼠信号蛋白基因(Agouti)的多态性及不同颜色被毛皮肤组织中Agouti与小眼畸形相关转录因子基因(MITF)表达的定量分析%The Polymorphism of Agouti Signaling Protein Gene (Agouti) and the Expression of A gouti and Microphthalmia-associated Transcription Factor Gene MITF in Different Coat Color Skin Tissues of Tibetan Sheep (Ovis aries)

    Institute of Scientific and Technical Information of China (English)

    韩吉龙; 岳耀敬; 裴杰; 郭婷婷; 刘建斌; 郭健; 孙晓萍; 冯瑞林; 杨博辉

    2013-01-01

    为了研究决定藏羊不同颜色被毛形成的分子机制,首先对绵羊(Ovis aries)毛色的主要候选基因刺鼠信号蛋白基因(agouti signaling protein (ASIP) gene,Agouti)的多态性进行了检测,然后对该基因外显子2和外显子4的功能突变和该基因的拷贝数变异分别与毛色进行了相关性分析;同时开展实时荧光定量PCR检测皮肤组织中Agouti和小眼畸形相关转录因子基因(microphthalmia-associated transcriptionfactor,MITF) mRNA的相对表达量,分析同一基因在黑色眼圈、棕黑色颈部和白色体侧被毛皮肤组织的相对表达量差异,对两基因在同一个体同一颜色被毛皮肤组织表达量进行相关性分析.结果表明,A gouti基因的外显子的单核苷酸多态性(SNP)多态性与毛色不相关,该基因的拷贝数变异(CNV)与毛色也不相关.同一个体Agouti基因mRNA表达水平为棕黑色皮肤组织显著高于黑色和白色(P<0.05),MITF基因mRNA表达量为黑色皮肤组织显著高于棕黑色和白色(P<0.05).通过相关性分析得知,两基因在同一个体同一毛色皮肤组织内mRNA相对表达量无显著相关性.研究结果提示,Agouti基因的多态性与藏羊的毛色不具有相关关系,MITF基因mRNA表达量可能与藏羊眼圈周围黑色被毛相关,Agouti基因mRNA表达量、MITF基因mRNA表达量可能对颈部棕黑色被毛有一定作用,体侧部的白色毛与Agouti和MITF基因mRNA表达量无明显相关.%In order to study the molecular mechanism that determines the formation of the coat color in different coat color of Tibetan sheep(Ovis aries) skin tissues, agouti signaling protein gene (Agouti) as the main candidate gene about coat color, Agouti gene's polymorphisms were detected firstly, then associated coat color with the exon 2, exon 4 function mutations and the gene copy number variation (CNV) of Agouti, as well as the Real-time fluorescent quantitative PCR was adopted to detect mRNA's relative

  5. Dietary Calcium and Dairy Modulation of Oxidative Stress and Mortality in aP2-Agouti and Wild-type Mice

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    Antje Bruckbauer

    2009-08-01

    Full Text Available Oxidative and inflammatory stress have been implicated as major contributors to the aging process. Dietary Ca reduced both factors in short-term interventions, while milk exerted a greater effect than supplemental Ca. In this work, we examined the effects of life-long supplemental and dairy calcium on lifespan and life-span related biomarkers in aP2-agouti transgenic (model of diet-induced obesity and wild-type mice fed obesigenic diets until their death. These data demonstrate that dairy Ca exerts sustained effects resulting in attenuated adiposity, protection against age-related muscle loss and reduction of oxidative and inflammatory stress in both mouse strains. Although these effects did not alter maximum lifespan, they did suppress early mortality in wild-type mice, but not in aP2-agouti transgenic mice.

  6. Cyclic Lactam Hybrid α-MSH/Agouti-Related Protein (AGRP) Analogues with Nanomolar Range Binding Affinities at the Human Melanocortin Receptors

    OpenAIRE

    Mayorov, Alexander V.; Cai, Minying; Palmer, Erin S.; Tanaka, Dustin K.; Cain, James P.; Dedek, Matthew M.; Tan, Bahar; Trivedi, Dev; Victor J. Hruby

    2011-01-01

    A novel hybrid melanocortin pharmacophore was designed based on the topographical similarities between the pharmacophores of Agouti related protein (AGRP) an endogenous melanocortin antagonist, and α-melanocyte-stimulating hormone (α-MSH), an endogenous melanocortin agonist. When employed in two different 23-membered macrocyclic lactam peptide templates, the designed hybrid AGRP/MSH pharmacophore yielded non-competitive ligands with nanomolar range binding affinities. The topography-based pha...

  7. Who's behind that mask and cape? The Asian leopard cat's Agouti (ASIP) allele likely affects coat colour phenotype in the Bengal cat breed.

    Science.gov (United States)

    Gershony, L C; Penedo, M C T; Davis, B W; Murphy, W J; Helps, C R; Lyons, L A

    2014-12-01

    Coat colours and patterns are highly variable in cats and are determined mainly by several genes with Mendelian inheritance. A 2-bp deletion in agouti signalling protein (ASIP) is associated with melanism in domestic cats. Bengal cats are hybrids between domestic cats and Asian leopard cats (Prionailurus bengalensis), and the charcoal coat colouration/pattern in Bengals presents as a possible incomplete melanism. The complete coding region of ASIP was directly sequenced in Asian leopard, domestic and Bengal cats. Twenty-seven variants were identified between domestic and leopard cats and were investigated in Bengals and Savannahs, a hybrid with servals (Leptailurus serval). The leopard cat ASIP haplotype was distinguished from domestic cat by four synonymous and four non-synonymous exonic SNPs, as well as 19 intronic variants, including a 42-bp deletion in intron 4. Fifty-six of 64 reported charcoal cats were compound heterozygotes at ASIP, with leopard cat agouti (A(P) (be) ) and domestic cat non-agouti (a) haplotypes. Twenty-four Bengals had an additional unique haplotype (A2) for exon 2 that was not identified in leopard cats, servals or jungle cats (Felis chaus). The compound heterozygote state suggests the leopard cat allele, in combination with the recessive non-agouti allele, influences Bengal markings, producing a darker, yet not completely melanistic coat. This is the first validation of a leopard cat allele segregating in the Bengal breed and likely affecting their overall pelage phenotype. Genetic testing services need to be aware of the possible segregation of wild felid alleles in all assays performed on hybrid cats. PMID:25143047

  8. Who's behind that mask and cape? The Asian leopard cat's Agouti (ASIP) allele likely affects coat colour phenotype in the Bengal cat breed.

    Science.gov (United States)

    Gershony, L C; Penedo, M C T; Davis, B W; Murphy, W J; Helps, C R; Lyons, L A

    2014-12-01

    Coat colours and patterns are highly variable in cats and are determined mainly by several genes with Mendelian inheritance. A 2-bp deletion in agouti signalling protein (ASIP) is associated with melanism in domestic cats. Bengal cats are hybrids between domestic cats and Asian leopard cats (Prionailurus bengalensis), and the charcoal coat colouration/pattern in Bengals presents as a possible incomplete melanism. The complete coding region of ASIP was directly sequenced in Asian leopard, domestic and Bengal cats. Twenty-seven variants were identified between domestic and leopard cats and were investigated in Bengals and Savannahs, a hybrid with servals (Leptailurus serval). The leopard cat ASIP haplotype was distinguished from domestic cat by four synonymous and four non-synonymous exonic SNPs, as well as 19 intronic variants, including a 42-bp deletion in intron 4. Fifty-six of 64 reported charcoal cats were compound heterozygotes at ASIP, with leopard cat agouti (A(P) (be) ) and domestic cat non-agouti (a) haplotypes. Twenty-four Bengals had an additional unique haplotype (A2) for exon 2 that was not identified in leopard cats, servals or jungle cats (Felis chaus). The compound heterozygote state suggests the leopard cat allele, in combination with the recessive non-agouti allele, influences Bengal markings, producing a darker, yet not completely melanistic coat. This is the first validation of a leopard cat allele segregating in the Bengal breed and likely affecting their overall pelage phenotype. Genetic testing services need to be aware of the possible segregation of wild felid alleles in all assays performed on hybrid cats.

  9. Trichostrongylina (Nematoda, Heligmosomoidea coparasites in Dasyprocta fuliginosa Wagler (Rodentia, Dasyproctidae from Brazil, with the re-establishment of the genus Avellaria Freitas & Lent and the description of two new species Trichostrongylina (Nematoda, Heligmosomoidea co-parasitos em Dasyprocta fuliginosa Wagler (Rodentia, Dasyproctidae do Brasil, com o restabelecimento do gênero Avellaria Freitas & Lent e a descrição de duas novas espécies

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    Marie C. Durette-Desset

    2006-06-01

    Full Text Available Two new tichostrongylid nematodes of the family Viannaiidae Durette-Desset & Chabaud, 1981 coparasites in Dasyprocta fuliginosa Wagler, 1832 from the State of Amazonas, Brazil, are described: Viannella trichospicula sp. nov. is differentiated from the other species of the genus by the extreme slenderness of its spicules. Avellaria intermedia sp. nov. is distinguished from the single type species Avellaria avellari Freitas & Lent, 1934, by a smaller number of cuticular ridges (17 versus 27, a higher ratio of spicule length/ body length (8% versus 5.6% and spicules with a single tip. This genus, synonymized with the genus Viannella Travassos, 1918, by Durette-Desset (1968 is re-established, the female being didelphic. It is the first record of a nematode of the family Viannaiidae in a host of the family Dasyproctidae Bonaparte, 1838.Dois novos nematóides tricostrongilídeos da família Viannaiidae Durette-Desset & Chabaud, 1981 co-parasitos em um espécime de Dasyprocta fuliginosa Wagler, 1832 do Estado do Amazonas, Brasil, são descritos: Viannella trichospicula sp. nov. distingue-se das espécies do gênero, pelos espículos extremamente delgados. Avellaria intermedia sp. nov. diferencia-se da espécie tipo e única do gênero Avellaria avellari Freitas & Lent, 1934, pelo menor número de arestas cuticulares (17 comparado a 27, pela maior relação entre o tamanho do espículo e o comprimento do corpo (8% comparado a 5,6% e espículos com extremidade única. Este gênero, que havia sido considerado sinônimo de Viannella Travassos, 1918, por Durette-Desset (1968, é restabelecido; as fêmeas são didelfas. Este é o primeiro registro de um nematóide da família Viannaiidae em um hospedeiro da família Dasyproctidae Bonaparte, 1838.

  10. [The influence of hyperleptinemia during pregnancy on fetal weight and obesity development in progeny mice with agouti yellow mutation].

    Science.gov (United States)

    Makarova, E N; Syracheva, M S; Bazhan, N M

    2014-03-01

    Maternal obesity increases the risk of obesity in the offspring, and obesity is accompanied by an increase in blood leptin levels. Leptin can influence the progeny metabolism via its influence on fetal growth and, possibly, via its action on AgRP expression in placenta. The "yellow" mutation at the mouse agouti locus (A(y)) evokes obesity and increases blood leptin levels in pregnant mice. The aim was to examine the influence of A(y) mutation in pregnant mice on fetal weight, placental expression of AgRP gene and food intake and obesity development in progeny. A(y) pregnant females as compared to control ones had increased circulating leptin levels on days 13 and 18 of pregnancy. Both fetal weight and placental expression of AgRP gene were increased on day 13 of pregnancy and decreased on day 18 of pregnancy in A(y) females as compared to control ones. Both control (a/a) and obesity prone (A(y)/a) male young born to A(y) mothers had lowered body weight and enhanced food intake between 5 and 11 weeks of age as compared to male progeny of control mothers. The enhanced leptin levels during pregnancy in mice are associated with retardation of obesity development in obesity prone male offspring and with changes in fetal weight and AgRP gene expression in placenta.

  11. Histochemical characterization, distribution and morphometric analysis of NADPH diaphorase neurons in the spinal cord of the agouti

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    Marco Aurelio M Freire

    2008-05-01

    Full Text Available We evaluated the neuropil distribution of the enzymes NADPH diaphorase (NADPH-d and cytochrome oxidase (CO in the spinal cord of the agouti, a medium-sized diurnal rodent, together with the distribution pattern and morphometrical characteristics of NADPH-d reactive neurons across different spinal segments. Neuropil labeling pattern was remarkably similar for both enzymes in coronal sections: reactivity was higher in regions involved with pain processing. We found two distinct types of NADPH-d reactive neurons in the agouti’s spinal cord: type I neurons had large, heavily stained cell bodies while type II neurons displayed relatively small and poorly stained somata. We concentrated our analysis on type I neurons. These were found mainly in the dorsal horn and around the central canal of every spinal segment, with a few scattered neurons located in the ventral horn of both cervical and lumbar regions. Overall, type I neurons were more numerous in the cervical region. Type I neurons were also found in the white matter, particularly in the ventral funiculum. Morphometrical analysis revealed that type I neurons located in the cervical region have dendritic trees that are more complex than those located in both lumbar and thoracic regions. In addition, NADPH-d cells located in the ventral horn had a larger cell body, especially in lumbar segments. The resulting pattern of cell body and neuropil distribution is in accordance with proposed schemes of segregation of function in the mammalian spinal cord.

  12. Disulfide assignment of the C-terminal cysteine knot of agouti-related protein (AGRP) by direct sequencing analysis.

    Science.gov (United States)

    Young, Y; Zeni, L; Rosenfeld, R D; Stark, K L; Rohde, M F; Haniu, M

    1999-12-01

    We have assigned the disulfide structure of Md-65 agouti-related protein (Md65-AGRP) using differential reduction and alkylation followed by direct sequencing analysis. The mature human AGRP is a single polypeptide chain of 112 amino acid residues, consisting of an N-terminal acidic region and a unique C-terminal cysteine-rich domain. The C-terminal domain, a 48 amino acid peptide named Md65-AGRP, was expressed in Escherichia coil cells and refolded under different conditions from the mature recombinant protein. The disulfide bonds in the cystine knot structure of Md65-AGRP were partially reduced using tris(2-carboxyethyl) phosphine (TCEP) under acidic conditions, followed by alkylation with N-ethylmaleimide (NEM). The procedure generated several isoforms with varying degrees of NEM alkylation. The multiple forms of Md65-AGRP generated by partial reduction and NEM modification were then completely reduced and carboxymethylated to identify unreactive disulfide bonds. Differentially labeled Md65-AGRP were directly sequenced and analyzed by MALDI mass spectrometry. The results confirmed that Md65-AGRP contained the same disulfide structure as that of Md5-AGRP reported previously [Bures, E. J., Hui, J. O., Young, Y. et al. (1998) Biochemistry 37, 12172-12177].

  13. INDUCCIÓN SINCRÓNICA DEL CICLO ESTRAL EN LA GUAGUA NEGRA (Agouti taczanowskii EN CAUTIVERIO SYNCHRONOUS INDUCTION OF THE ESTRAL CYCLE IN THE BLACK GUAGUA (Agouti taczanowskii IN CAPTIVITY

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    Luis Emilio Trujillo Aramburo

    2006-06-01

    Full Text Available Para la inducción y sincronización del ciclo estral en la guagua negra Agouti taczanowskii en cautiverio, se aplicó a cada una de seis hembras, con edades entre cuatro y siete años, un cuarto de dosis de norgestomet y 1,25 mg de valerato de estradiol. A partir del día de la aplicación del implante se les realizó medición del diámetro del orificio vulvar tres veces por semana hasta el día 52 y con igual frecuencia, a partir del día del retiro del implante, se realizó muestreo sanguíneo para determinar los niveles de progesterona por radioinmunoanálisis. El tratamiento hormonal indujo y sincronizó el ciclo estral en tres de las seis hembras tratadas, las cuales presentaron aumento en los niveles de progesterona ³ 10 ng/ml precedidos de apertura del orificio vulvar. El ciclo estral inducido tuvo una duración variable entre 11 y 29 días. El ciclo estral espontáneo que se presentó después del inducido con el tratamiento hormonal, presentó duración variable entre 10 y 30 días. Durante el tiempo de experimentación se presentó una correlación negativa entre los niveles de progesterona y el diámetro de la apertura vulvar. Se concluye que la aplicación de un implante de norgestomet acompañado de una inyección de valerato de estradiol puede inducir y sincronizar el ciclo estral en la guagua negra.To induce and synchronize the estral cycle in the black guagua Agouti taczanowskii in captivity, each of six females varying from four to seven years of age were implanted with a quarter dose of norgestomet and injected with 1,25 mg of estradiol valerate. Starting on the day of the application of the implant, the diameter of the vulvar orifice was measured three times per week until day 52, and with same frequency beginning on the day the implant was removed, blood sampling was conducted to determine progesterone levels for radioimunoassay. The hormonal treatment induced and synchronized the estral cycle in three of the six treated

  14. The high glycemic index diet was an independent predictor to explain changes in agouti-related protein in obese adolescents

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    Bárbara Dal Molin Netto

    2014-02-01

    Full Text Available The high glycemic index diet was an independent predictor to explain changes in agouti-related protein in obese adolescents. Background & Aims: The role of diet glycemic index (GI in the control of orexigenic and anorexigenic factors of the energy balance is still not clear. The present study aimed to assess whether the habitual diet, according to different GI foods, exerts influence on regulation of energy balance markers and the effects of interdisciplinary intervention in obese adolescents. Methods: A total of 55 obese adolescents, aged from 14 to 19 years, were submited to one year of interdisciplinary therapy and were divided in two groups, according to the predominant dietary pattern of food intake: high-GI group (H-GI; n = 29 and moderate/low-GI group (M/L-GI; n = 26. Results: The concentration of orexigenic factor AgRP (p < 0.01, visceral fat (p=0.04 and visceral/subcutaneous ratio (p = 0.03 were higher in the group of H-GI when compared with M/L-GI group. Moreover, the habitual consumption of H-GI foods was an independent predictor to explain changes in AgRP concentrations. After one year of interdisciplinary therapy, the adolescents presented significant reductions in body weight, total body fat (%, visceral and subcutaneous fat and HOMA-IR, as well as a significant increase of fat free mass (%. Conclusions: Our results may suggest that habitual H-GI diet could upregulate orexigenic pathways, contributing to vicious cycle between undesirable diets, deregulates energy balance and predispose to obesity. One the other hand, one year of interdisciplinary therapy can significant improves metabolic profile and central obesity in adolescents.

  15. Hypothalamic Agouti-Related Peptide mRNA is Elevated During Natural and Stress-Induced Anorexia.

    Science.gov (United States)

    Dunn, I C; Wilson, P W; D'Eath, R B; Boswell, T

    2015-09-01

    As part of their natural lives, animals can undergo periods of voluntarily reduced food intake and body weight (i.e. animal anorexias) that are beneficial for survival or breeding, such as during territorial behaviour, hibernation, migration and incubation of eggs. For incubation, a change in the defended level of body weight or 'sliding set point' appears to be involved, although the neural mechanisms reponsible for this are unknown. We investigated how neuropeptide gene expression in the arcuate nucleus of the domestic chicken responded to a 60-70% voluntary reduction in food intake measured both after incubation and after an environmental stressor involving transfer to unfamiliar housing. We hypothesised that gene expression would not change in these circumstances because the reduced food intake and body weight represented a defended level in birds with free access to food. Unexpectedly, we observed increased gene expression of the orexigenic peptide agouti-related peptide (AgRP) in both incubating and transferred animals compared to controls. Also pro-opiomelanocortin (POMC) mRNA was higher in incubating hens and significantly increased 6 days after exposure to the stressor. Conversely expression of neuropeptide Y and cocaine- and amphetamine-regulated transcript gene was unchanged in both experimental situations. We conclude that AgRP expression remains sensitive to the level of energy stores during natural anorexias, which is of adaptive advantage, although its normal orexigenic effects are over-ridden by inhibitory signals. In the case of stress-induced anorexia, increased POMC may contribute to this inhibitory role, whereas, for incubation, reduced feeding may also be associated with increased expression in the hypothalamus of the anorexigenic peptide vasoactive intestinal peptide. PMID:26017156

  16. Copy number variation and missense mutations of the agouti signaling protein (ASIP) gene in goat breeds with different coat colors.

    Science.gov (United States)

    Fontanesi, L; Beretti, F; Riggio, V; Gómez González, E; Dall'Olio, S; Davoli, R; Russo, V; Portolano, B

    2009-01-01

    In goats, classical genetic studies reported a large number of alleles at the Agouti locus with effects on coat color and pattern distribution. From these early studies, the dominant A(Wt) (white/tan) allele was suggested to cause the white color of the Saanen breed. Here, we sequenced the coding region of the goat ASIP gene in 6 goat breeds (Girgentana, Maltese, Derivata di Siria, Murciano-Granadina, Camosciata delle Alpi, and Saanen), with different coat colors and patterns. Five single nucleotide polymorphisms (SNPs) were identified, 3 of which caused missense mutations in conserved positions of the cysteine-rich carboxy-terminal domain of the protein (p.Ala96Gly, p.Cys126Gly, and p.Val128Gly). Allele and genotype frequencies suggested that these mutations are not associated or not completely associated with coat color in the investigated goat breeds. Moreover, genotyping and sequencing results, deviation from Hardy-Weinberg equilibrium, as well as allele copy number evaluation from semiquantitative fluorescent multiplex PCR, indicated the presence of copy number variation (CNV) in all investigated breeds. To confirm the presence of CNV and evaluate its extension, we applied a bovine-goat cross-species array comparative genome hybridization (aCGH) experiment using a custom tiling array based on bovine chromosome 13. aCGH results obtained for 8 goat DNA samples confirmed the presence of CNV affecting a region of less that 100 kb including the ASIP and AHCY genes. In Girgentana and Saanen breeds, this CNV might cause the A(Wt) allele, as already suggested for a similar structural mutation in sheep affecting the ASIP and AHCY genes, providing evidence for a recurrent interspecies CNV. However, other mechanisms may also be involved in determining coat color in these 2 breeds.

  17. Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene.

    Science.gov (United States)

    Jethwa, P H; Warner, A; Fowler, M J; Murphy, M; de Backer, M W; Adan, R A H; Barrett, P; Brameld, J M; Ebling, F J P

    2010-06-01

    Many vertebrates express profound annual cycles of body fattening, although it is not clear whether these represent differential activity of the central pathways known to mediate homeostatic control of food intake and energy expenditure, or whether the recent discovery of a major role for pars tuberalis-ependymal signalling points towards novel mechanisms. We examined this in the Siberian hamster (Phodopus sungorus) by using gene transfection to up-regulate a major orexigenic peptide, agouti-related peptide (AgRP), and then determined whether this increased anabolic drive could prevent the short-day induced winter catabolic state. Infusions of a recombinant adeno-associated virus encoding an AgRP construct into the hypothalamus of hamsters in the long-day obese phase of their seasonal cycle produced a 20% gain in body weight over 6 weeks compared to hamsters receiving a control reporter construct, reflecting a significant increase in food intake and a significant decrease in energy expenditure. However, all hamsters showed a significant, prolonged decrease in body weight when exposed to short photoperiods, despite the hamsters expressing the AgRP construct maintaining a higher food intake and lower energy expenditure relative to the control hamsters. Visualisation of the green fluorescent protein reporter and analysis of AgRP-immunoreactivity confirmed widespread expression of the construct in the hypothalamus, which was maintained for the 21-week duration of the study. In conclusion, the over-expression of AgRP in the hypothalamus produced a profoundly obese state but did not block the seasonal catabolic response, suggesting a separation of rheostatic mechanisms in seasonality from those maintaining homeostasis of energy metabolism.

  18. UN ÍNDICE PARA LA EVALUACIÓN DEL HÁBITAT DE AGOUTI TACZANOWSK/1 (RODENTIA: AGOUTIDAE) EN ÁREAS DE BOSQUE ANDINO NUBLADO

    OpenAIRE

    Jairo Pérez-Torres

    2002-01-01

    Se presenta un índice que permitirá evaluar el hábitat de la "Lapa andiim" o "Tinajo" (Agouti taczanowskii) en zonas de bosque andino nublado. El objetivo fundamental de este índice, es obtener elementos que sirvan para la toma de decisiones en cuanto al diseño de áreas de reserva y planes de manejo sobre esta especie. Este índice se basa en la aplicación de criterios tanto cualitativos como cuantitativos, los cuales son tabulados y computados para sacar un valor de calidad de hábitat para ca...

  19. Dietary Calcium and Dairy Modulation of Oxidative Stress and Mortality in aP2-Agouti and Wild-type Mice

    OpenAIRE

    Antje Bruckbauer; Zemel, Michael B

    2009-01-01

    Oxidative and inflammatory stress have been implicated as major contributors to the aging process. Dietary Ca reduced both factors in short-term interventions, while milk exerted a greater effect than supplemental Ca. In this work, we examined the effects of life-long supplemental and dairy calcium on lifespan and life-span related biomarkers in aP2-agouti transgenic (model of diet-induced obesity) and wild-type mice fed obesigenic diets until their death. These data demonstrate that dairy Ca...

  20. Electroacupuncture Improves Insulin Resistance by Reducing Neuroprotein Y/Agouti-Related Protein Levels and Inhibiting Expression of Protein Tyrosine Phosphatase 1B in Diet-induced Obese Rats.

    Science.gov (United States)

    Liu, Xia; He, Jun-Feng; Qu, Ya-Ting; Liu, Zhi-Jun; Pu, Qing-Yang; Guo, Sheng-Tong; Du, Jia; Jiang, Peng-Fei

    2016-04-01

    Electroacupuncture (EA) has been shown to exert beneficial effects on obesity, but the mechanism is unclear. This study investigated the effects of EA on diet-induced obese (DIO) rats. Fifty male Sprague-Dawley rats were randomly divided into low-fat diet (LFD, 10 rats) and high-fat diet (HFD, 40 rats) groups. After the DIO models had been established, successful model rats were randomly divided into HFD, EA, and orlistat (OLST) groups. The EA group received EA at Zusanli (ST36) and Quchi (LI11) for 20 minutes once per day for 28 days. The OLST group was treated with orlistat by gavage. The body weight, homeostasis model assessment-insulin resistance index, adipocyte diameters, and neuroprotein Y/agouti-related protein and protein tyrosine phosphatase 1B levels were significantly lower in the EA group than in the HFD group. The rats of the OLST group showed watery stools and yellow hairs whereas those of the EA group had regular stools and sleek coats. The effect of EA on weight loss may be related to improved insulin resistance caused by changes in the adipocyte size and by reductions in the expressions of neuroprotein Y/agouti-related protein and protein tyrosine phosphatase 1B. This study indicates that EA may be a better method of alternative therapy for treating obesity and other metabolic diseases. PMID:27079226

  1. The high glycemic index diet was an independent predictor to explain changes in agouti-related protein in obese adolescents.

    Science.gov (United States)

    Dal Molin Netto, Bárbara; Landi Masquio, Deborah Cristina; Da Silveira Campos, Raquel Munhoz; De Lima Sanches, Priscila; Campos Corgosinho, Flavia; Tock, Lian; Missae Oyama, Lila; Túlio de Mello, Marco; Tufik, Sergio; Dâmaso, Ana Raimunda

    2014-02-01

    La Dieta de alto índice glucémico es un predictor independiente para explicar los cambios en la proteína relacionada al agouti en adolescentes obesos. Introducción y objetivos: El papel de la dieta de índice glucémico (GI) en el control de los factores orexigénicos y anorexígenos del balance de energía todavía no está claro. El presente estudio tuvo como objetivo evaluar si la dieta habitual, de acuerdo con diferentes alimentos con IG, ejerce influencia sobre la regulación de los marcadores del balance de energía y los efectos de la intervención interdisciplinaria en adolescentes obesos. Métodos: Un total de 55 adolescentes obesos, con edades de 14 a 19 años, han sido sometidos a un año de tratamiento interdisciplinario y se dividieron en dos grupos, de acuerdo al patrón de dieta predominante de la ingesta de alimentos: el grupo IG alto (H-GI; n = 29) y GI moderada/bajo grupo (M/L-GI, n = 26). Resultados: La concentración de orexigenic factor de AgRP (p consumo habitual de alimentos H-GI fue un predictor independiente para explicar los cambios en las concentraciones de AgRP. Después de un año de tratamiento interdisciplinario, los adolescentes presentan una reducción significativa en el peso corporal, la grasa corporal total (%), visceral y la grasa subcutánea y el HOMA-IR, así como un aumento significativo de la masa libre de grasa (%). Conclusiones: Nuestros resultados pueden sugerir que la dieta H-GI habitual podría upregulate vías orexigénicos, contribuyendo al círculo vicioso entre las dietas indeseables, desregula el equilibrio energético y predisponen a la obesidad. Uno por otro lado, un año de tratamiento interdisciplinario puede perfil metabólico mejora significativa y la obesidad central en los adolescentes.

  2. Solid-Phase Peptide Head-to-Side Chain Cyclodimerization: Discovery of C2-Symmetric Cyclic Lactam Hybrid α-Melanocyte-Stimulating Hormone (MSH)/Agouti-Signaling Protein (ASIP) Analogues with Potent Activities at the Human Melanocortin Receptors

    OpenAIRE

    Mayorov, Alexander V.; Cai, Minying; Palmer, Erin S.; Liu, Zhihua; Cain, James P.; Vagner, Josef; Trivedi, Dev; Victor J. Hruby

    2010-01-01

    A novel hybrid melanocortin pharmacophore was designed based on the pharmacophores of the Agouti signaling protein (ASIP), an endogenous melanocortin antagonist, and α-melanocyte-stimulating hormone (α-MSH), an endogenous melanocortin agonist. The designed hybrid ASIP/MSH pharmacophore was explored in monomeric cyclic, and cyclodimeric templates. The monomeric cyclic disulfide series yielded peptides with hMC3R-selective non-competitive binding affinities. The direct on-resin peptide lactam c...

  3. Leishmaniose cutânea na Amazônia: isolamento de Leishmania (Viannia lainsoni do roedor Agouti paca (Rodentia: Dasyproctidae, no estado do Pará, Brasil Cutaneous leishmaniasis in the Amazon Region: isolation of Leishmania (Viannia lainsoni from the rodent Agouti paca (Rodentia: Dasyproctidae in Pará State, Brazil

    Directory of Open Access Journals (Sweden)

    Fernando T. Silveira

    1991-02-01

    Full Text Available Fez-se o registro, pela primeira vez, do isolamento de Leishmania (V. lainsoni de um mamífero silvestre, o roedor Agouti paca (Rodentia: Dasyproctidae, no Estado do Pará, Brasil. As amostras do parasita foram isoladas da pele, aparentemente íntegra, de 3 espécimes desse roedor, capturados no município de Tucuruí (ilha de Tocantins, em área que seria inundada pela formação do lago da hidrelétrica construída naquele município. Nenhum isolamento foi obtido de vísceras de qualquer dos animais. A identificação das amostras de L. (V. lainsoni baseou-se na morfologia de amastigotas e promastigotas, no comportamento da infecção em "hamsters", na análise bioquímica de isoenzimas e, ainda, através de testes com anticorpos monoclonais. A natureza inaparente da infecção nos animais faz supor que o mamífero em questão possa representar um hospedeiro definitivo do parasita na região Amazônica.The isolation of Leishmania (V. lainsoni is recorded for the first time from a wild animal, the rodent Agouti paca (Rodentia: Dasyproctidae, from Pará State, north Brazil. Isolates of the parasite were made from apparently normal skin of 3 specimens of this rodent captured on the Island of Tocantins, in the municipality of Tucuruí, an area subsequently flooded in the formation of the lake associated with the Tucuruí hydroeletric dam. No isolations were made from the viscera. Identification of the parasite was in each case based on morphology of the amastigotes and promastigotes, behavior of the organism in hamsters, isoenzymes profiles and the use of monoclonal antibodies. The inapparent nature of the infection leads us to suggest that the "paca", Agouti paca, represents a primitive host of L. (V. lainsoni in the Amazon Region.

  4. Distinct Roles for JNK and IKK Activation in Agouti-Related Peptide Neurons in the Development of Obesity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Eva Tsaousidou

    2014-11-01

    Full Text Available Activation of c-Jun N-terminal kinase 1 (JNK1- and inhibitor of nuclear factor kappa-B kinase 2 (IKK2-dependent signaling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. Here, we demonstrate that constitutive JNK activation in agouti-related peptide (AgRP-expressing neurons of the hypothalamus is sufficient to induce weight gain and adiposity in mice as a consequence of hyperphagia. JNK activation increases spontaneous action potential firing of AgRP cells and causes both neuronal and systemic leptin resistance. Similarly, activation of IKK2 signaling in AgRP neurons also increases firing of these cells but fails to cause obesity and leptin resistance. In contrast to JNK activation, IKK2 activation blunts insulin signaling in AgRP neurons and impairs systemic glucose homeostasis. Collectively, these experiments reveal both overlapping and nonredundant effects of JNK- and IKK-dependent signaling in AgRP neurons, which cooperate in the manifestation of the metabolic syndrome.

  5. Co-infections of the cestode Echinococcus vogeli and the nematode Calodium hepaticum in the hystricomorphic rodent Agouti paca from a forest reserve in Acre, Brazil.

    Science.gov (United States)

    Almeida, F; Caldas, R; Corrêa, C; Rodrigues-Silva, R; Siqueira, N; Machado-Silva, J R

    2013-12-01

    The helminth fauna of Agouti paca (Linnaeus, 1766) has seldom been studied. In this paper, we report an unusual mixed infection of Echinococcus vogeli Rausch & Bernstein, 1972 and Calodium hepaticum (syn. Capillaria hepatica Bancroft, 1863) in free-ranging paca from a forested region in Acre (Brazil). Gross morphological examination revealed that paca liver contained multiple spherical to subspherical white or translucent lesions, which were isolated or frequently contiguous and partially covered by Glisson's capsule. Microscopic examination revealed unilocular cystic structures that contained abundant brood capsules in which numerous protoscolices budded from the inner surface. The protoscolices possessed rostellar hooks (33-41 μm in length), a morphological characteristic of the blade and calcareous corpuscles that is consistent with the metacestode E. vogeli. The diagnosis of C. hepaticum infection was based on the morphology and morphometry of the egg-shaped ellipsoids with bipolar plugs (44.8 ± 1.9 μm (length) × 24.4 ± 2.0 μm (width)) and liver histopathology. This finding expands the known range of C. hepaticum hosts in South America and, to the best of our knowledge, it is the first case of a mixed infection of E. vogeli and C. hepaticum. Furthermore, our data provide evidence that wild animal meat may be a source of C. hepaticum infection.

  6. Anorexigenic and Orexigenic Hormone Modulation of Mammalian Target of Rapamycin Complex 1 Activity and the Regulation of Hypothalamic Agouti-Related Protein mRNA Expression

    Directory of Open Access Journals (Sweden)

    Kenneth R. Watterson

    2012-03-01

    Full Text Available Activation of mammalian target of rapamycin 1 (mTORC1 by nutrients, insulin and leptin leads to appetite suppression (anorexia. Contrastingly, increased AMP-activated protein kinase (AMPK activity by ghrelin promotes appetite (orexia. However, the interplay between these mechanisms remains poorly defined. The relationship between the anorexigenic hormones, insulin and leptin, and the orexigenic hormone, ghrelin, on mTORC1 signalling was examined using S6 kinase phosphorylation as a marker for changes in mTORC1 activity in mouse hypothalamic GT1-7 cells. Additionally, the contribution of AMPK and mTORC1 signalling in relation to insulin-, leptin- and ghrelin-driven alterations to mouse hypothalamic agouti-related protein (AgRP mRNA levels was examined. Insulin and leptin increase mTORC1 activity in a phosphoinositide-3-kinase (PI3K- and protein kinase B (PKB-dependent manner, compared to vehicle controls, whereas increasing AMPK activity inhibits mTORC1 activity and blocks the actions of the anorexigenic hormones. Ghrelin mediates an AMPK-dependent decrease in mTORC1 activity and increases hypothalamic AgRP mRNA levels, the latter effect being prevented by insulin in an mTORC1-dependent manner. In conclusion, mTORC1 acts as an integration node in hypothalamic neurons for hormone-derived PI3K and AMPK signalling and mediates at least part of the assimilated output of anorexigenic and orexigenic hormone actions in the hypothalamus.

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

    Science.gov (United States)

    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. Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose.

    Science.gov (United States)

    Hao, Lihong; Sheng, Zhenyu; Potian, Joseph; Deak, Adam; Rohowsky-Kochan, Christine; Routh, Vanessa H

    2016-10-01

    A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast. Mice which express green fluorescent protein (GFP) on their NPY promoter were used to identify NPY/AgRP neurons. Fasting for 24h and LPS injection decreased blood glucose levels. As we have found previously, fasting increased c-fos expression in NPY/AgRP neurons and increased the activation of NPY/AgRP-GI neurons by decreased glucose. As we predicted, LPS blunted these effects of fasting at the 24h time point. Moreover, the inflammatory cytokine tumor necrosis factor alpha (TNFα) blocked the activation of NPY/AgRP-GI neurons by decreased glucose. These data suggest that LPS and TNFα may alter glucose and energy homeostasis, in part, due to changes in the glucose sensitivity of NPY/AgRP neurons. Interestingly, our findings also suggest that NPY/AgRP-GI neurons use a distinct mechanism to sense changes in extracellular glucose as compared to our previous studies of GI neurons in the adjacent ventromedial hypothalamic nucleus.

  9. Establishment and assessment of rheumatoid arthritis model induced by pristane in Dark-Agouti rats%降植烷诱导的DA大鼠类风湿性关节炎模型的建立和评估

    Institute of Scientific and Technical Information of China (English)

    张利文; 文凯; 袁泉

    2013-01-01

    Objective: To establish animal model of rheumatoid arthritis( RA) and measure the indexes for RA,to provide evidence for reseach and clinical treatments of RA. Methods; The present study was performed on the Dark-Agouti (DA) rats. The RA model was induced by intracutaneous injection of pristane (300 fjul) into the root of the tail. The body weight, pathological score for joints, paw volume, motion of joint, mechanical withdrawal threshold (MWT) , heat withdrawal latency (HWL) were examined before and after the establishment of the RA model. Results; Arthritic manifestations occurred in all the DA rats 7-14 days after injection of pristane,including joint swelling in metacarpophalangeal joints, interphalangeal joint and ankle joint, increase in paw volume, trouble walking, decline in range of motion, decrease in mechanical withdrawal threshold, and so on. All these manifestations reached the peak at 21-28 days. Conclusion; The RA model induced by pristane in DA rats have some characteristics such as high incidence,simple operation,similar to the patients with RA. Thus,it could be conclude that pristane induced arthritis (PIA) model in DA rats is a better model for RA.%目的:建立大鼠类风湿性关节炎(rheumatoid arthritis,RA)模型及检测相关指标,为研究RA的发病机制及其临床治疗提供依据.方法:本研究以Dark-Agouti (DA)大鼠为模型动物,采用尾根部皮内一次性注射降植烷300μl的方法建立RA模型,并检测不同时间点大鼠体重、关节病理评分、爪容积、后爪关节活动度、机械缩爪阈值、热缩爪潜伏期等指标.结果:注射降植烷后7 ~ 14 d DA大鼠100%发病,表现为四肢掌指关节、指间关节以及踝关节红肿,爪容积增加,动物行走障碍,关节活动度下降,机械缩爪阈值明显下降,第21~28天达高峰.结论:降植烷尾根部注射引起的DA大鼠关节炎发病率高,操作简单易行,与临床RA患者表现有高度相似性,是一种较好的RA模型.

  10. Polymorphism of Agouti Signaling Protein Gene in Guizhou Pony, Southwest Horse and ILi Horse%贵州矮马、西南马和伊犁马刺豚鼠信号蛋白基因的多态性

    Institute of Scientific and Technical Information of China (English)

    党珍; 王嘉福; 赵星艳; 田松军; 黄勇; 冉雪琴

    2011-01-01

    为了探索贵州矮马、西南马、伊犁马刺豚鼠信号蛋白( Agouti signaling protein,ASIP)基因与马品种毛色之间的关系,采用缺口PCR技术分析了141份贵州矮马、西南马、伊犁马的ASIP基因型,并进行克隆测序.结果表明,扩增出的793 bp和385 bp 2个片段为ASIP基因,793 bp片段中缺失一段11 bp的核苷酸,定义为a基因型,385 bp片段结构完整,定义为A基因型;3个马群体中A等位基因在骝毛中占优势;但aa基因型对应的毛色只有小部分为黑毛,绝大部分为栗毛、骝毛和复色毛,与已知的aa基因型决定黑毛的规律不相符,说明aa基因型可能不是中国马品种黑毛的决定基因型.%The ASIP genotypes of 141 samples from Guizhou pony, Southwest horse and Ili horse were analyzed by the gap PCR and their sequence was determined by the cloning technique to study the relationship between ASIP gene and hair color. The results show that amplified 793bp and 385bp fragments are named as ASIP genes, the nucleotide of 793 bp fragment with 11 bp deletion and intact 385 bp structure are defined as a genotype and A genotype respectively, A allele is the dominant in bay hair of three horse populations but the hair of most horses with the aa genotype is chestnut, bay and complex color and only a small number of horses with the aa genotype is of black hair color, which does not quite match with the regularity of black hair color controlled by the aa genotype. Therefore, the black hair color of indigenous Chinese horse may not be controlled by the aa genotype.

  11. An Autochthonous Case of Echinococcus vogeli Rausch & Bernstein, 1972 Polycystic Echinococcosis in the State of Rondônia, Brazil

    Directory of Open Access Journals (Sweden)

    Rosângela Rodrigues-Silva

    2002-01-01

    Full Text Available The present case report refers to a patient from the State of Rondônia, North region of Brazil, attended with clinical suspicion of hepatic echinococcosis. Examination by imaging (ultrasonography and computerized tomography revealed a conglomerate of cystic lesions, with mobile contents within the cyst. The serology (immunoblot for Echinococcus sp. was positive (21 and 31 kDa bands. This case is the first reported in Rondônia, suggesting the need to investigate the polycystic echinococcosis in individuals with hepatic cysts from areas of tropical forest and hunting habits where wild life was present as wild dogs, cats and rodents, particularly Agouti paca (paca and Dasyprocta aguti (agouti.

  12. Discovery of a β-Hairpin Octapeptide, c[Pro-Arg-Phe-Phe-Dap-Ala-Phe-DPro], Mimetic of Agouti-Related Protein(87-132) [AGRP(87-132)] with Equipotent Mouse Melanocortin-4 Receptor (mMC4R) Antagonist Pharmacology.

    Science.gov (United States)

    Ericson, Mark D; Wilczynski, Andrzej; Sorensen, Nicholas B; Xiang, Zhimin; Haskell-Luevano, Carrie

    2015-06-11

    Agouti-related protein (AGRP) is a potent orexigenic peptide that antagonizes the melanocortin-3 and -4 receptors (MC3R and MC4R). While the C-terminal domain of AGRP, AGRP(87-132), is equipotent to the full-length peptide, further truncation decreases potency at the MC3R and MC4R. Herein, we report AGRP-derived peptides designed to mimic the active β-hairpin secondary structure that contains the hypothesized Arg-Phe-Phe pharmacophore. The most potent scaffold, c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro], comprised the hexa-peptide β-hairpin loop from AGRP cyclized through a DPro-Pro motif. A 20 compound library was synthesized from this scaffold for further structure-activity relationship studies. The most potent peptide from this library was an asparagine to diaminopropionic acid substitution that possessed sub-nanomolar antagonist activity at the mMC4R and was greater than 160-fold selective for the mMC4R versus the mMC3R. The reported ligands may serve as probes to characterize the melanocortin receptors in vivo and leads in the development of novel therapeutics. PMID:25898270

  13. Serological survey for Leishmania sp. infection in wild animals from the municipality of Maringá, Paraná state, Brazil

    Directory of Open Access Journals (Sweden)

    EM Voltarelli

    2009-01-01

    Full Text Available Leishmania sp. infection was investigated in wild animals from the Ingá Park, in the municipality of Maringá, Paraná state, Brazil, where American cutaneous leishmaniasis (ACL is an endemic disease. Sixty-five mammals, comprising Didelphis albiventris, Cerdocyon thous, Lycalopex vetulus, Cebus apella, Dasyprocta azarae, Dasypus novemcinctus, Procyon cancrivorus and Nasua nasua, were captured. Blood samples were collected for parasite cultivation. Antibodies were investigated by direct agglutination test (DAT using Leishmania (Viannia braziliensis as antigen. Flagellates were observed in blood cultures of 14 (35.9% Didelphis albiventris. Anti-Leishmania antibodies were detected in 31 (51.6% specimens of Cerdocyon thous, Lycalopex vetulus, Cebus apella, Dasyprocta azarae, Procyon cancrivorus and Nasua nasua. These results suggest that Cerdocyon thous and Lycalopex vetulus (crab-eating fox, Cebus apella (capuchin monkey, Dasyprocta azarae (agouti, Procyon cancrivorus (crab-eating raccoon and Nasua nasua (coati play an important role in the ACL transmission cycle in the northwestern region of Paraná, Brazil.

  14. Ecological Relationships of Meso-Scale Distribution in 25 Neotropical Vertebrate Species

    Science.gov (United States)

    Michalski, Lincoln José; Norris, Darren; de Oliveira, Tadeu Gomes; Michalski, Fernanda

    2015-01-01

    Vertebrates are a vital ecological component of Amazon forest biodiversity. Although vertebrates are a functionally important part of various ecosystem services they continue to be threatened by anthropogenic impacts throughout the Amazon. Here we use a standardized, regularly spaced arrangement of camera traps within 25km2 to provide a baseline assessment of vertebrate species diversity in a sustainable use protected area in the eastern Brazilian Amazon. We examined seasonal differences in the per species encounter rates (number of photos per camera trap and number of cameras with photos). Generalized linear models (GLMs) were then used to examine the influence of five variables (altitude, canopy cover, basal area, distance to nearest river and distance to nearest large river) on the number of photos per species and on functional groups. GLMs were also used to examine the relationships between large predators [Jaguar (Panthera onca) and Puma (Puma concolor)] and their prey. A total of 649 independent photos of 25 species were obtained from 1,800 camera trap days (900 each during wet and dry seasons). Only ungulates and rodents showed significant seasonal differences in the number of photos per camera. The number of photos differed between seasons for only three species (Mazama americana, Dasyprocta leporina and Myoprocta acouchy) all of which were photographed more (3 to 10 fold increase) during the wet season. Mazama americana was the only species where a significant difference was found in occupancy, with more photos in more cameras during the wet season. For most groups and species variation in the number of photos per camera was only explained weakly by the GLMs (deviance explained ranging from 10.3 to 54.4%). Terrestrial birds (Crax alector, Psophia crepitans and Tinamus major) and rodents (Cuniculus paca, Dasyprocta leporina and M. acouchy) were the notable exceptions, with our GLMs significantly explaining variation in the distribution of all species

  15. Light microscope observations on the epididymis of paca (Agouti paca).

    Science.gov (United States)

    Schimming, Bruno Cesar; Machado, Márcia Rita Fernandes; Simões, Karina; da Cruz, Claudinei; Domeniconi, Raquel Fantin

    2013-01-01

    The features of paca epididymis, based on its appearance in light microscope, is described in this paper. The cellular population of the epithelial lining comprises principal cells, basal cells, apical cells, narrows cells, and hallo cells. The epididymis is divided in five distinct and continuous regions, Zone I, or initial segment, and zone II, are both localized into the head. Zone III comprises the distal head and all the body. Zones IV and V are restricted to the tail, in the proximal and distal cauda epididymis respectively. Each zone can be readily distinguished on the basis of morphological characteristics. The height of epididymal epithelium is greater in zone I. There is a progressive increase in the diameter of the tubular lumen through the different areas, with the maximum in the zone V. The presence of a high epithelium, and the virtual absence of sperm in zone I suggest fast transit of spermatozoa in this region. Zone V comprises the distal tail, has smaller epithelial lining, greater luminal diameter, shorter stereocilia than the other zones, and contains spermatozoa packed inside the lumen, that characterizes this zone as a place of sperm storage. The findings are compared with other reports in rodents and other domestic animals, to contribute to the understanding of epididymal morphophysiology.

  16. Agouti-related protein prevents self-starvation

    NARCIS (Netherlands)

    Kas, M J H; van Dijk, G; Scheurink, A J W; Adan, R A H

    2003-01-01

    Food restriction leads to a paradoxical increase in physical activity and further suppression of food intake, such as observed in anorexia nervosa.(1,2) To understand this pathophysiological process, we induced physical hyperactivity and self-starvation in rats by restricting food in the presence of

  17. Uniparidade em pacas criadas em cativeiro (Agouti paca, Linnaeus, 1766 Uniparity in pacas bred in captivity (Agouti paca, Linnaeus, 1766

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    F.S. Oliveira

    2007-04-01

    Full Text Available Durante quatro anos foram detectadas 25 prenhezes, em 13 diferentes pacas, por meio de ultra-sonografia. Após a detecção ultra-sonográfica, as fêmeas foram separadas em baias individuais para o nascimento dos filhotes e aí mantidas até o desmame. Houve nascimento de apenas um animal por parto, ressaltando a característica reprodutiva de uniparidade, o que sugere a tendência de nascimento de apenas um filhote por parto, nessa espécie.During four years 25 pregnancies were detected in 13 different pacas by means of ultrasonography at a wild animal section. After ultrasound detection, females were separated in individual sets for delivering and kept until weaning of newborns. Only one newborn by delivery occurred, remarking the reproductive characteristic of uniparity, what suggests the trend of only one newborn in each delivery.

  18. Mammal Hunting in the Special Use Zone and Buffer Tingo Maria National Park, Huánuco, Peru

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    Fiorella Nasha Gonzales Guillén

    2014-12-01

    Full Text Available Between the months of August to November 2011 were conducted 42 semi-structured interviews to assess the hunting of mammals in areas of special purpose (ZUE and buffer (ZA National Park Tingo María surveys. The results indicate that 43% of the population practiced hunting as a secondary activity, the main smallholder agriculture. The methodology used for hunting are the "tramperas" while the hunting is often 2-3 times a month. Hunting is more common after the wet season, it is selective and responds to the taste of meat that an economic need. Among the most hunted mammals include agouti Dasyprocta sp. and picuro Cuniculus paca, while animals higher biomass as the peccary Pecari tajacu are rare in the area, so it is recommended to increase the control of hunting of vulnerable species in the villages which are inside and in the vicinity of the Park.

  19. Zygomycetes from herbivore dung in the ecological reserve of Dois Irmãos, Northeast Brazil

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    André Luiz Cabral Monteiro de Azevedo Santiago

    2011-03-01

    Full Text Available Thirty-eight taxa of Zygomycetes distributed in 15 genera were recorded from tapir (Tapirus terrestris, camel (Camelus bactrianus, horse (Equus caballus, deer (Cervus elaphus, agouti (Dasyprocta aguti, donkey (Equus asinus, llama (Llama glama and waterbuck (Kobus ellipsiprymnus dung collected at the Reserva Ecológica de Dois Irmãos located in Recife, State of Pernambuco, Northeast Brazil. The samples were collected on a monthly basis from June 2005 to May 2006, taken to the laboratory and incubated in moist chambers. Higher number of taxa was observed in the excrements of tapir, followed by deer and donkey. The highest number of species was detected for Mucor, followed by Pilobolus. Statistical analyses showed significant differences in richness of Zygomycetes taxa between the herbivore dung types. Differences of species composition, however, were weak. Seasonality influenced the Zygomycetes species composition but not its richness. Variations in taxa composition between ruminants and non-ruminants dung were non significant.

  20. The roles of ghrelin/agouti-related protein/peptide YY signal pathway in gastric bypass operation for type 2 diabetes%胃饥饿素/肽YY/刺鼠相关蛋白信号在胃旁路手术治疗2型糖尿病中的作用

    Institute of Scientific and Technical Information of China (English)

    高寅生; 侯亚勃; 杨晓军; 高鹏; 曹农

    2016-01-01

    Objective To study the roles of ghrelin,agouti-related protein (AGRP) and peptide YY (PYY) signal in treatment of type 2 diabetes mellitus by gastric bypass operation.Methods Twenty adult SD rats were used to establish the model of type 2 diabetes mellitus,and divided into 2 groups:No operation group (NO,n =10) and Roux-en-Y gastric bypass operation group (RYGB,n =10),and another ten adult rats were used as the Normal Control group (NC,n =10).The RYGB group were performed operation after the rat model of type 2 diabetes mellitus were established successfully.The blood were separately collected to examine ghrelin,blood sugar,cholesterol and triglyceride before and after operation,and we monitored the consumption of food and water everyday.The hypothalamus tissues were collected at the 4th week after operation to examine the expression of AGRP and PYY mRNA.Results At the 4th week after operation,the blood sugar dropped to (6.18 ±0.77) mmol/L,Triglycerides dropped to (2.45 ±0.23) mmol/L;Cholesterol dropped to (2.07 ± 0.22) mmoL/L and the consumption of food,water of RYGB group were nearly down to normal level.The level of ghrelin dropped to (410.60 ± 58.33) ng/L,AGRP mRNA dropped to 0.80 ±0.13 in hypothalamus were lower than NO group after operation,the level of PYY mRNA rised to 1.60 ± 0.25 were significantly increased (P < 0.05).Conclusion We can conclude that the situation of type 2 diabetes mellitus can be controlled by Roux-en-Y gastric bypass operation.Ghrelin may regulate the energy metabolism of type 2 diabetes mellitus via AGRP and PYY signals.Our results suggest that the roles of ghrelin,AGRP and PYY signals may play an important role in the control of type 2 diabetes mellitus after Roux-en-Y gastric bypass operation.%目的 探讨胃饥饿素(Ghrelin)、肽YY(PYY)、刺鼠相关蛋白(AGRP)信号通路在胃旁路手术治疗2型糖尿病中的作用及其机制.方法 采用20只成年SD雄性大鼠成功建立2型糖尿病大鼠模型,随机分

  1. Genetic Effect of Tyrosinase (TYR), Microphthalmia-associated Transcription Factor (MITF) and Agouti Signaling Protein (ASIP) Genes on Melanin Deposition of White Silky Fowl (Gallus gallus domesticus Brisson)%酪氨酸酶(TYR)、小眼畸形相关转录因子(MITF)和刺鼠信号蛋白(ASIP)基因对白绒乌骨鸡黑色素沉积的遗传效应

    Institute of Scientific and Technical Information of China (English)

    郑嫩珠; 李丽; 辛清武; 缪中纬; 朱志明; 陈黎; 刘凤辉; 吴剑飞; 黄勤楼

    2015-01-01

    为研究白绒乌骨鸡(Gallus gallus domesticus Brisson)黑色素沉积分子机制,本研究采用实时荧光定量PCR(quantitative Real-time PCR,qRT-PCR)的2-△△Ct检测酪氨酸酶(tyrosinase,TYR)、刺鼠信号蛋白(agouti signaling protein,ASIP)和小眼畸形相关转录因子(microphthalmia-associated transcription factor,MITF)基因在乌骨鸡皮肤、肌肉、肝脏、肾脏和肌胃的表达情况,采用紫外分光光度法测定不同组织黑色素含量,探索3个基因在不同组织中mRNA表达量与黑色素沉积之间的关系.结果表明,TYR、MITF和ASIP在所有组织中均有表达,且各基因mRNA相对表达量在各组织间差异极显著(P<0.01),其中MITF和TYR mRNA表达量依次为皮肤>肾脏>肌胃>肝脏>肌肉,与乌骨鸡各组织黑色素沉积规律基本一致;ASIP基因表达量则与其相反,表现为肌肉>肝脏>肌胃>肾脏>皮肤.相关性分析表明,TYR和MITF基因在各个组织中的表达量与其黑色素含量呈显著正相关(P<0.05),ASIP基因表达量与其呈显著负相关(P<0.05).由此提示,TYR、MITF和ASIP与白绒乌骨鸡黑色素沉积均具有一定的相关性,其中TYR和MITF基因的高表达可能促进乌骨鸡黑色素沉积,ASIP则相反.本研究为进一步阐明黑色素沉积的遗传调控机制提供了理论基础.

  2. Wild Rodents as Experimental Intermediate Hosts of Lagochilascaris minor Leiper, 1909

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    Julieta Machado Paçô

    1999-07-01

    Full Text Available A total of 25 specimens of Cavia porcellus (guinea pig, 5 Dasyprocta agouti (agouti, and 22 Calomys callosus (vesper mice were inoculated with infective eggs of Lagochilascaris minor. The inoculum was prepared with embryonated eggs and orally administered to each individual animal through an esophagus probe. In parallel, 100 specimens of Felis catus domesticus were individually fed with 55-70 nodules containing 3rd-stage larvae encysted in tissues of infected rodents. Animals were examined and necropsied at different time intervals. The migration and encystment of L3 larva was observed in viscera, skeletal muscle, adipose and subcutaneous tissues from all rodents. Adult worms localized at abscesses in the cervical region, rhino, and oropharynx were recovered from domestic cats inoculated with infected rodent tissues. Through this study we can conclude that: (1 wild rodents act as intermediate hosts, characterizing this ascarid heteroxenic cycle; (2 in natural conditions rodents could possibly act as either intermediate hosts or paratenic hosts of Lagochilascaris minor; (3 despite the occurrence of an auto-infecting cycle, in prime-infection of felines (definite hosts the cycle is only completed when intermediate hosts are provided; and (4 in the wild, rodents could serve as a source of infection for humans as they are frequently used as food in regions with the highest incidence of human lagochilascariasis.

  3. Utilização dos recursos naturais por comunidades humanas do Parque Ecoturístico do Guamá, Belém, Pará Utilization of natural resources by the human communities of the Guamá Ecotouristic Park, Belém, Pará

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    Ana Sílvia Sardinha Ribeiro

    2007-06-01

    Full Text Available O trabalho apresenta dados sobre o uso dos recursos naturais por populações humanas em pequenas comunidades (vilas localizadas no entorno (n = 6 e no interior (n = 1 do Parque Ecoturístico do Guamá (PEG, visando avaliar os impactos sobre a fauna e flora local, ante a implantação de um projeto de infra-estrutura rodoviária local. A metodologia consistiu da aplicação de dois modelos de questionários. Um direcionado a pessoas-chave, como: moradores mais antigos, presidentes de associações, agentes de saúde, etc, e o outro aplicado aleatoriamente aos adultos locais. Buscou-se atingir pelo menos 50% das famílias das pequenas localidades (11 famílias. Em todos os casos é realizado o extrativismo da fauna e flora, principalmente com o objetivo de subsistência. As espécies mais caçadas foram Agouti paca,Dasyprocta agouti,Nasua nasua, Euphractus sexcintus e Hydrochaeris hydrochaeris. A complementação da renda familiar através do comércio de caça sob encomenda é realizada em todas as comunidades estudadas. Frutíferas como Euterpe oleracea Mart., Musa spp e Theobroma cacao foram encontradas em 100% das comunidades (n=7. Plantas medicinais são rotineiramente cultivadas e empregadas. As espécies madeireiras exploradas são utilizadas com o objetivo de produção de carvão, construção de casas e de meios de transporte, predominando o Inga edulis, Virola surinamensis (Rol. Warb e Simaruba amara (Aubl.. O trabalho discute os resultados sob o aspecto da implantação do projeto viário, oferecendo recomendações para a minimização dos impactos do mesmo sobre a fauna, a flora e o modo tradicional de vida das comunidades.This work shows data about the use of natural resources by the human population located in (n=1 and around (n=6 the Guamá Ecotouristic Park (GEP, in order to evaluate the impact on the local fauna and flora in view of the project for constructing a road through the park. The methodology utilized in this community

  4. Agouti-related peptide plays a critical role in leptin's effects on female puberty and reproduction

    OpenAIRE

    Sheffer-Babila, Sharone; Sun, Yan; Israel, Davelene D.; Liu, Shun-Mei; Neal-Perry, Genevieve; Streamson C Chua

    2013-01-01

    Deficient leptin signaling causes infertility via reduced activity of GnRH neurons, causing a hypogonadal state in both rodents and humans. Because GnRH neurons do not express leptin receptors, leptin's effect on GnRH neurons must be indirect. Neurons within the hypothalamic arcuate nucleus that coexpress AGRP and NPY are considered to be important intermediate neurons involved in leptin regulation of GnRH neurons. Previously, we reported that the absence of AGRP and haploinsufficiency of MC4...

  5. Scatter hoarding by the Central American agouti: a test of optimal cache spacing theory

    NARCIS (Netherlands)

    Gálvez, D.; Kranstauber, B.; Kays, R.W.; Jansen, P.A.

    2009-01-01

    Optimal cache spacing theory predicts that scatter-hoarding animals store food at a density that balances the gains of reducing cache robbery against the costs of spacing out caches further. We tested the key prediction that cache robbery and cache spacing increase with the economic value of food: t

  6. Scatter hoarding by the Central American agouti : a test of optimal cache spacing theory

    NARCIS (Netherlands)

    Galvez, Dumas; Kranstauber, Bart; Kays, Roland W.; Jansen, Patrick A.

    2009-01-01

    Optimal cache spacing theory predicts that scatter-hoarding animals store food at a density that balances the gains of reducing cache robbery against the costs of spacing out caches further. We tested the key prediction that cache robbery and cache spacing increase with the economic value of food: t

  7. Morphology of accessory genital glands of spotted paca (Agouti paca Linnaeus, 1766).

    Science.gov (United States)

    Borges, Edson Moreira; Branco, Érika; de Lima, Ana Rita; Leal, Leonardo Martins; Martins, Leandro Luiz; Reis, Ana Carolina Gonçalves; Cruz, Claudinei; Machado, Márcia Rita Fernandes; Miglino, Maria Angelica

    2014-02-01

    The spotted paca is the second largest rodent in Brazil, where it is of great economic interest in impoverished regions in view of its prominence as a low-cost source of protein. Little is known about the morphology of the accessory genital glands of this species. Thus, we studied the position and morphology of the genitals in ten adult male spotted pacas. The animals were divided into two groups, five animals were used for fixing of samples in 10% aqueous formaldehyde for macroscopic studies and the other five animals were designated for microscopic analysis. These were arranged in pairs and had the vesicular, prostate, coagulating and bulbourethral glands identified, being structured as mucous glands, which lead into the pelvic urethra. It was concluded that the accessory genital glands found in the paca are the same as those found in most rodents, showing similar histological aspects.

  8. Scatter hoarding of seeds confers survival advantages and disadvantages to large-seeded tropical plants at different life stages.

    Directory of Open Access Journals (Sweden)

    Erin K Kuprewicz

    Full Text Available Scatter hoarding of seeds by animals contributes significantly to forest-level processes, including plant recruitment and forest community composition. However, the potential positive and negative effects of caching on seed survival, germination success, and seedling survival have rarely been assessed through experimental studies. Here, I tested the hypothesis that seed burial mimicking caches made by scatter hoarding Central American agoutis (Dasyprocta punctate enhances seed survival, germination, and growth by protecting seeds from seed predators and providing favorable microhabitats for germination. In a series of experiments, I used simulated agouti seed caches to assess how hoarding affects seed predation by ground-dwelling invertebrates and vertebrates for four plant species. I tracked germination and seedling growth of intact and beetle-infested seeds and, using exclosures, monitored the effects of mammals on seedling survival through time. All experiments were conducted over three years in a lowland wet forest in Costa Rica. The majority of hoarded palm seeds escaped predation by both invertebrates and vertebrates while exposed seeds suffered high levels of infestation and removal. Hoarding had no effect on infestation rates of D. panamensis, but burial negatively affected germination success by preventing endocarp dehiscence. Non-infested palm seeds had higher germination success and produced larger seedlings than infested seeds. Seedlings of A. alatum and I. deltoidea suffered high mortality by seed-eating mammals. Hoarding protected most seeds from predators and enhanced germination success (except for D. panamensis and seedling growth, although mammals killed many seedlings of two plant species; all seedling deaths were due to seed removal from the plant base. Using experimental caches, this study shows that scatter hoarding is beneficial to most seeds and may positively affect plant propagation in tropical forests, although

  9. Scatter hoarding of seeds confers survival advantages and disadvantages to large-seeded tropical plants at different life stages.

    Science.gov (United States)

    Kuprewicz, Erin K

    2015-01-01

    Scatter hoarding of seeds by animals contributes significantly to forest-level processes, including plant recruitment and forest community composition. However, the potential positive and negative effects of caching on seed survival, germination success, and seedling survival have rarely been assessed through experimental studies. Here, I tested the hypothesis that seed burial mimicking caches made by scatter hoarding Central American agoutis (Dasyprocta punctate) enhances seed survival, germination, and growth by protecting seeds from seed predators and providing favorable microhabitats for germination. In a series of experiments, I used simulated agouti seed caches to assess how hoarding affects seed predation by ground-dwelling invertebrates and vertebrates for four plant species. I tracked germination and seedling growth of intact and beetle-infested seeds and, using exclosures, monitored the effects of mammals on seedling survival through time. All experiments were conducted over three years in a lowland wet forest in Costa Rica. The majority of hoarded palm seeds escaped predation by both invertebrates and vertebrates while exposed seeds suffered high levels of infestation and removal. Hoarding had no effect on infestation rates of D. panamensis, but burial negatively affected germination success by preventing endocarp dehiscence. Non-infested palm seeds had higher germination success and produced larger seedlings than infested seeds. Seedlings of A. alatum and I. deltoidea suffered high mortality by seed-eating mammals. Hoarding protected most seeds from predators and enhanced germination success (except for D. panamensis) and seedling growth, although mammals killed many seedlings of two plant species; all seedling deaths were due to seed removal from the plant base. Using experimental caches, this study shows that scatter hoarding is beneficial to most seeds and may positively affect plant propagation in tropical forests, although tradeoffs in seed

  10. Seed predation by mammals in forest fragments in Monteverde, Costa Rica.

    Science.gov (United States)

    Chinchilla, Federico A

    2009-09-01

    Few studies have evaluated seed predation in fragmented landscapes, in which lower species diversity is expected to modifying ecological interactions. The rates of seed removal by mammals were investigated in a continuous forest and two fragmented patches of Premontane Tropical Moist Forest, in Monteverde, Costa Rica. The composition of mammalian seed-predators in each site was recorded during 16 months. The removal of four native tree species of experimental seeds: Ocotea valeriana and Ocotea whitei (Lauraceae), Panopsis costaricensis (Proteaceae) and Billia colombiana (Hippocastanaceae) in forest understories was followed during two annual fruiting seasons for each species. Results indicated similar species composition of seed-predators between continuous forest, the largest fragment (350 ha). However the smaller fragment (20 ha), had fewer seed predators. In this fragment, the specialized seed predator Heteromys desmarestianus (Rodentia) was more abundant. Unexpectedly, seed-predation in the two forest fragments and the continuous forest did not differ statistically for any of the seed species. Apparently, the higher abundance of small seed-predators in the fragments was compensated by the absence of medium and large seed-predators, like Agouti paca, Dasyprocta punctata (both Rodentia) and Pecari tajacu (Artiodactyla) recorded in continuous forest. Removal of experimentally-placed seeds was higher when the number of naturally occurring seeds in the sites was lower. This result could best be attributed to differential satiation of seed predators rather than differences in richness or abundance of seed predators.

  11. Le mini-élevage, son développement villageoiset l'action de BEDIM

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    Jacques Hardouin

    1997-01-01

    Full Text Available Minilivestock, village development and the role of BEDIM.Minilivestock encompasses all animals of small site, and little-known in terras of production but usable as food, feed or revenues if not eaten. Sustainable breeding becomes possible, and should progressively replace uncontrolled gathering in the wild. Amongst vertebrates, an important meat supply is based on edible rodents like Thryonomys, Cricetomys, Xerus, Atherurus, Tenrec; Hydrochoerus, Dasyprocta, Myocastor, Capromys, Dolichotis, Agouti, etc. The saine applies to the guinea-pig Cavia porcellus and to frogs. Invertebrates farming is also practised through breeding of maggots, termites, butterflies (pupae and adults for consumption or sale; giant snails are also highly appreciated in many African countries. Minilivestock development is usually a back-yard activity, hence its interest as it relies on local species, substrates and raw materials for infrastructure. The demand for minilivestock product is high but there is still reluctance often from the official authorities, unfortunately. However minilivestock is not an utopia, and a country like Papua-New-Guinea, which bas officially adopted minilivestock production as a tool to help to develop remote villages, is an excellent example of success

  12. Molecular identification of trypanosomatids in wild animals.

    Science.gov (United States)

    Tenório, M S; Oliveira e Sousa, L; Alves-Martin, M F; Paixão, M S; Rodrigues, M V; Starke-Buzetti, W A; Araújo Junior, J P; Lucheis, S B

    2014-06-16

    Diverse wild animal species can be reservoirs of zoonotic flagellate parasites, which can cause pathologic Chagas disease. The present study aimed to detect the natural occurrence of flagellate parasites through direct microscopic examination of the parasites in blood samples and through PCR of whole blood and blood culture (haemoculture) samples from 38 captive and 65 free-living wild animals in the Centre for Conservation of Wild Fauna (CCWF), an area endemic for leishmaniasis. For this study, PCR was accomplished using primers for the ribosomal region (ITS-1) of the flagellate parasites. The amplified fragments were cloned and sequenced to identify DNA of the Trypanosomatid parasite species, observed in blood cultures from 3.9% (04/103) of the animals. Through these techniques, Trypanosoma cruzi was identified in haemoculture samples of the following three free-living species: common agouti (Dasyprocta aguti), white-eared opossum (Didelphis albiventris), and nine-banded armadillo (Dasypus novemcinctus). Furthermore, Trypanosoma minasense was identified in whole blood samples from 01 (0.9%) captive animal (black howler monkey-Alouatta caraya). These results demonstrated the first report of T. cruzi isolation in wild species from the CCWF using blood culture, which can be applied in addition to molecular tools for epidemiological studies and to identify trypanosomatids in wild animals. PMID:24636787

  13. PESO PÓS-PARTO, FREQÜÊNCIA E PREVALÊNCIA DO TIPO DE PARTO DE CUTIAS (Dasyprocta sp) CRIADAS EM CATIVEIRO

    OpenAIRE

    Maria Acelina Martins Carvalho; Airton Mendes Conde Júnior; Luís Madeira Martins Júnior; Sandovaldo Gonçalves de Moura; Mônica Marcos de Almeida; Rildênio Renato Cavalcante; João Batista Lopes

    2006-01-01

    A pesquisa objetivou avaliar parâmetros de desenvolvimento de cutias, buscando fornecer dados para contribuir com a seleção, o melhoramento genético e formas adequadas de manejo para estes animais. Foram observados o peso pós-parto, freqüência e a prevalência do tipo de parto em função da época do ano em 33 fêmeas. Constatou-se que não houve interação entre época do ano e tipo de parto (P>0,05). O peso médio pós-parto foi de 2,24 Kg e 2,39 Kg, para o período de janeiro a dezembro, respecti...

  14. PESO PÓS-PARTO, FREQÜÊNCIA E PREVALÊNCIA DO TIPO DE PARTO DE CUTIAS (Dasyprocta sp CRIADAS EM CATIVEIRO

    Directory of Open Access Journals (Sweden)

    Maria Acelina Martins de Carvalho

    2006-10-01

    Full Text Available A pesquisa objetivou avaliar parâmetros de desenvolvimento de cutias, buscando fornecer dados para contribuir com a seleção, o melhoramento genético e formas adequadas de manejo para estes animais. Foram observados o peso pós-parto, freqüência e a prevalência do tipo de parto em função da época do ano em 33 fêmeas. Constatou-se que não houve interação entre época do ano e tipo de parto (P>0,05. O peso médio pós-parto foi de 2,24 Kg e 2,39 Kg, para o período de janeiro a dezembro, respectivamente, não apresentando diferença significativa para esta variável (P>0,05. Com relação ao tipo de parto, as cutias com parto simples apresentaram peso médio de 2,32 Kg e as com parto duplo 2,38 Kg, não sendo estes valores significativamente diferentes entre si (P>0,05. Concluiu-se que o peso da cutia fêmea pós-parto, a freqüência e o tipo de parto (simples e duplos não sofrem influência da época do ano e que a cutia em cativeiro se comporta como poliéstrica contínua. PALAVRAS-CHAVE: Cutia, peso pós-parto, prevalência, tipo de parto.

  15. Efeito das atividades de ecoturismo sobre a riqueza e a abundância de espécies de mamíferos de médio e grande porte na região do Cristalino, Mato Grosso, Brasil Effect of ecotourism activities on richness and abundance of species of medium and large mammals in the Cristalino region, Mato Grosso, Brazil

    Directory of Open Access Journals (Sweden)

    Ednaldo Cândido Rocha

    2012-12-01

    Full Text Available Este estudo foi desenvolvido nas Reservas Particulares do Patrimônio Natural Cristalino (670 ha e Lote Cristalino (6.539 ha e no Parque Estadual Cristalino (184.900 ha. Essas unidades de conservação são contíguas e estão localizadas no extremo centro-norte do estado do Mato Grosso, em locais considerados prioritários para a conservação, em função da alta biodiversidade e endemismos, além da elevada pressão antrópica. Desta forma, este trabalho objetivou conhecer, avaliar e comparar a estrutura das populações de mamíferos de médio e grande porte, em termos de riqueza e abundância das espécies em ambientes sem turismo e com atividades de ecoturismo na região do Cristalino. Para tanto, no período compreendido entre maio de 2008 a fevereiro de 2010 foram amostrados ambientes com floresta primária, os quais apresentavam dois níveis de perturbação antrópica: sem turismo e com atividades de ecoturismo. Os dados foram coletados utilizando a amostragem de distâncias em transecções lineares, que totalizou 468,3 Km percorridos nos períodos diurno e noturno, e registro de pegadas em parcelas previamente preparadas (n = 660 parcelas vistoriadas, além de percursos fluviais no rio Cristalino e buscas aleatórias nos locais onde não ocorriam caminhos. Registros de 37 espécies de mamíferos foram obtidos, sendo 33 de médio e grande porte e quatro de pequeno porte. Não houve diferença estatisticamente significativa na riqueza de espécies dos ambientes sem turismo e com ecoturismo, sendo que a similaridade de espécies entre eles foi alta (88%. No entanto, três táxons apresentaram abundância inferior nos ambientes com turismo: Dasyprocta leporina (Linnaeus, 1766, Mazama spp. e Dasypus kappleri Krauss, 1862. Percebe-se, portanto, que o impacto negativo das atividades de ecoturismo desenvolvidas na área de estudo foi de pequena magnitude, em termos de riqueza e abundância de mamíferos de médio e grande porte. Assim

  16. Rhizobium grahamii sp. nov., from nodules of Dalea leporina, Leucaena leucocephala and Clitoria ternatea, and Rhizobium mesoamericanum sp. nov., from nodules of Phaseolus vulgaris, siratro, cowpea and Mimosa pudica.

    Science.gov (United States)

    López-López, Aline; Rogel-Hernández, Marco A; Barois, Isabelle; Ortiz Ceballos, Angel I; Martínez, Julio; Ormeño-Orrillo, Ernesto; Martínez-Romero, Esperanza

    2012-09-01

    Two novel related Rhizobium species, Rhizobium grahamii sp. nov. and Rhizobium mesoamericanum sp. nov., were identified by a polyphasic approach using DNA-DNA hybridization, whole-genome sequencing and phylogenetic and phenotypic characterization including nodulation of Leucaena leucocephala and Phaseolus vulgaris (bean). As similar bacteria were found in the Los Tuxtlas rainforest in Mexico and in Central America, we suggest the existence of a Mesoamerican microbiological corridor. The type strain of Rhizobium grahamii sp. nov. is CCGE 502(T) (= ATCC BAA-2124(T) = CFN 242(T) = Dal4(T) = HAMBI 3152(T)) and that of Rhizobium mesoamericanum sp. nov. is CCGE 501(T) (= ATCC BAA-2123(T) = HAMBI 3151(T) = CIP 110148(T) = 1847(T)). PMID:22081714

  17. Hemi-ovariossalpingohisterectomia em pacas prenhes e posterior ocorrência de prenhez (Agouti paca, Linnaeus, 1766 Hemiovarysalpingohysterectomy in pregnant pacas and further occurrency of pregnancy (Agouti paca, Linnaeus, 1766

    Directory of Open Access Journals (Sweden)

    Fabrício Singaretti de Oliveira

    2003-06-01

    Full Text Available Foi descrita a hemi-ovariossalpingohisterectomia em cinco pacas prenhes mantidas em cativeiro no Setor de Animais Silvestres da Faculdade de Ciências Agrárias e Veterinárias (FCAV-UNESP de Jaboticabal, São Paulo, Brasil, a fim de observar futura prenhez no corno restante. A tranqüilização foi obtida após aplicação de azaperone (4mg/kg seguida da aplicação de sulfato de atropina (0,06mg/kg e da associação de cloridrato de quetamina (20mg/kg e cloridrato de xilazina (1,5mg/kg, ambos na mesma seringa, para indução da anestesia. A anestesia geral foi obtida mediante inalação de halotano por máscara. Por meio de laparotomia mediana, foram retirados o corno uterino prenhe, o ovário e a tuba uterina, todos do mesmo antímero. Antibióticos (30.000UI/kg de três penicilinas e 12,5mg/kg de duas estreptomicinas e analgésico (0,02mg/kg de buprenorfina foram aplicados imediatamente após a cirurgia, sendo repetidos após dois dias. Todas as aplicações foram feitas por via intramuscular. Apesar da permanência de apenas um ovário após a cirurgia, nova prenhez ocorreu no corno restante nas cinco fêmeas submetidas à cirurgia, com o nascimento de filhotes (apenas um por parto após 215, 248, 276, 302 e 310 dias da hemi-ovariossalpingohisterectomia.The hemiovarysalpingohysterectomy in five captive pregnant pacas kept on the Wild Animal Section at the College of Agricultural and Veterinarian Sciences (FCAV-UNESP in Jaboticabal, São Paulo, Brazil, was conducted aiming at verifying the further occurrence of pregnancy on the remaining uterine horn. The tranquilization was achieved by using azaperone (4mg/kg and consequent application of atropine sulphate (0.06mg/kg and the association of ketamine (20mg/kg and xylazine (1.5mg/kg cloridrates, on the same syringe, for induction of anesthesia. The general anesthesia was performed via a face mask with halothane. By means of median laparotomy, the uterine horn with the fetus, the ovary and the uterine tube, all from the same antimere, were taken out. Antibiotics (30,000IU/kg of three penicillins and 12.5mg/kg of two streptomycins and analgesic (buprenorfine 0.02 mg/kg were injected immediately after surgery and repeated after two days. All injections were made intramuscularly. In spite of the permanence of only one ovary after surgery, new pregnancy occurred in the remaining uterine horn in the five females which went through surgery, and the birth (solely one by delivery happened 210, 248, 276, 302 and 310 days after the hemiovarysalpingohysterectomy.

  18. Hemi-ovariossalpingohisterectomia em pacas prenhes e posterior ocorrência de prenhez (Agouti paca, Linnaeus, 1766) Hemiovarysalpingohysterectomy in pregnant pacas and further occurrency of pregnancy (Agouti paca, Linnaeus, 1766)

    OpenAIRE

    Fabrício Singaretti de Oliveira; Gilson Hélio Toniollo; Márcia Rita Fernandes Machado; Daniela Paura

    2003-01-01

    Foi descrita a hemi-ovariossalpingohisterectomia em cinco pacas prenhes mantidas em cativeiro no Setor de Animais Silvestres da Faculdade de Ciências Agrárias e Veterinárias (FCAV-UNESP) de Jaboticabal, São Paulo, Brasil, a fim de observar futura prenhez no corno restante. A tranqüilização foi obtida após aplicação de azaperone (4mg/kg) seguida da aplicação de sulfato de atropina (0,06mg/kg) e da associação de cloridrato de quetamina (20mg/kg) e cloridrato de xilazina (1,5mg/kg), ambos na mes...

  19. ANÁLISE DA ORIGEM E DISTRIBUIÇÃO DOS NERVOS PERIFÉRICOS DO PLEXO BRAQUIAL DA PACA (Agouti paca, LINNAEUS, 1766) ORIGIN AND DITRIBUTION ANALYSIS OF THE BRACHIAL PLEXUS PERIPHERAL NERVES OF PACA (Agouti paca, LINNAEUS, 1766)

    OpenAIRE

    Sílvia Helena Brendolan Gerbasi; Fabrício Singaretti de Oliveira; Gregório Corrêa Guimarães; Márcia Rita Fernandes Machado; Alessandra Regina Freixo Scavone

    2008-01-01

    O plexo braquial é um conjunto de nervos que surge na região medular cervicotorácica e que se distribui pelos membros torácicos e porção interna do tórax. O plexo braquial de oito pacas foi dissecado para evidenciação da origem e distribuição de seus nervos. O nervo supraescapular distribuía-se para os músculos supra e infra-espinhal, e o subescapular para o músculo subescapular. O nervo axilar ramificava-se para os músculos redondo maior, subescapular, redondo menor e deltóide. Os nervos uln...

  20. Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness

    NARCIS (Netherlands)

    de Rijke, Corine E; Jackson, Pilgrim J; Garner, Keith M; van Rozen, Rea J; Douglas, Nick R; Kas, Martien J H; Millhauser, Glenn L; Adan, Roger A H

    2005-01-01

    AgRP is a neuropeptide that stimulates food intake through inhibition of central melanocortin receptors (MCRs). In humans, the non-conservative amino acid substitution Alanine (Ala) 67 Threonine (Thr) has been associated with Anorexia Nervosa and with leanness. In the present study, the cellular dis

  1. Seguimiento y monitoreo participativo de la actividad de cacería en la región de Puerto Nariño, Amazonas, Colombia

    Directory of Open Access Journals (Sweden)

    Rodríguez Carlos

    2004-12-01

    Full Text Available Se describen los patrones generales de la actividad de cacería en el casco urbano de Puerto Nariño a partir del registro continuo de las jornadas de caza durante el período de aguas ascendentes (enero-julio, 2003, a través de un análisis comparativo entre el aprovechamiento de fauna en las zonas de várzea y tierra firme, con una perspectiva integrada que incluye principios históricos, culturales y biológicos. Se determinan los parámetros de captura, esfuerzo y captura por unidad de esfuerzo (CPUE y se describe la composición y distribución de la captura. La captura total fue de 238 individuos correspondientes a 44 especies. Las especies
    con mayores valores de captura fueron Alouatta seniculus, Ara manilata y Phalacrocorax olivaceus, en la zona de várzea y en tierra firme fueron Agouti paca, Dasypus novemcinctus y Dasyprocta fuliginosa. Tomando la jornada como unidad de esfuerzo, se definen los tipos de jornada identificados, se analiza el esfuerzo perdido con base en las jornadas no exitosas y se describe la tipología de los cazadores. Entre algunos de los aspectos socioculturales que enmarcan la actividad de cacería, se describe la visión actual de la cacería por parte de los indígenas Ticuna de Puerto Nariño y los aspectos tradicionales que aún forman parte de esta actividad. El proyecto se abordó a través de una metodología participativa en la cual los pobladores locales se involucraron activamente en el monitoreo, proceso que permitió a los cazadores organizarse y continuar autónomamente con la toma de registros durante el período de aguas bajas.

  2. [Seasonal evaluation of mammal species richness and abundance in the "Mário Viana" municipal reserve, Mato Grosso, Brasil].

    Science.gov (United States)

    Rocha, Ednaldo Cândido; Silva, Elias; Martins, Sebastião Venâncio; Barreto, Francisco Cândido Cardoso

    2006-09-01

    We evaluated seasonal species presence and richness, and abundance of medium and large sized mammalian terrestrial fauna in the "Mário Viana" Municipal Biological Reserve, Nova Xavantina, Mato Grosso, Brazil. During 2001, two monthly visits were made to an established transect, 2,820 m in length. Records of 22 mammal species were obtained and individual footprint sequences quantified for seasonal calculation of species richness and relative abundance index (x footprints/km traveled). All 22 species occurred during the rainy season, but only 18 during the dry season. Pseudalopex vetulus (Lund, 1842) (hoary fox), Eira barbara (Linnaeus, 1758) (tayra), Puma concolor (Linnaeus, 1771) (cougar) and Hydrochaeris hydrochaeris (Linnaeus, 1766) (capybara) were only registered during the rainy season. The species diversity estimated using the Jackknife procedure in the dry season (19.83, CI = 2.73) was smaller than in the rainy season (25.67, CI = 3.43). Among the 18 species common in the two seasons, only four presented significantly different abundance indexes: Dasypus novemcinctus Linnaeus, 1758 (nine-banded armadillo), Euphractus sexcinctus (Linnaeus, 1758) (six-banded armadillo), Dasyprocta azarae Lichtenstein, 1823 (Azara's Agouti) and Tapirus terrestris (Linnaeus, 1758) (tapir). On the other hand, Priodontes maximus (Kerr, 1792) (giant armadillo) and Leopardus pardalis (Linnaeus, 1758) (ocelot) had identical abundance index over the two seasons. Distribution of species abundance in the sampled area followed the expected pattern for communities in equilibrium, especially in the rainy season, suggesting that the environment still maintains good characteristics for mammal conservation. The present study shows that the reserve, although only 470 ha in size, plays an important role for conservation of mastofauna of the area as a refuge in an environment full of anthropic influence (mainly cattle breeding in exotic pasture). PMID:18491629

  3. Both overexpression of agouti-related peptide or neuropeptide Y in the paraventricular nucleus or lateral hypothalamus induce obesity in a neuropeptide- and nucleus specific manner

    NARCIS (Netherlands)

    M.W.A. de Backer; S.E. la Fleur; R.A.H. Adan

    2011-01-01

    Both reduction of melanocortin signaling and increase in neuropeptide Y signaling in the brain result in obesity. However, where in the brain reduced melanocortin or increased neuropeptide Y signaling mediate these effects is poorly understood. In separate experiments we have injected recombinant ad

  4. Effects of Portabella mushrooms on collagen-induced arthritis, inflammatory cytokines, and body composition in dilute brown non-agouti (DBA1 mice

    Directory of Open Access Journals (Sweden)

    Stanley A. Lightfoot

    2011-09-01

    Full Text Available Background:Exotic mushrooms have long been used in Asia for treatment and/or prevention of chronic diseases due to their immunomodulatory properties. However, the health benefits of portabella mushrooms (PM (brown Agaricus bisporous, on collagen-induced arthritis (CIA and associated complications, (i.e. loss of lean mass, increased fat mass and inflammatory cytokines, have not been previously investigated.Methods:We investigated CIA pathogenesis, body composition and plasma levels of IL- 6, TNF-α and sICAM1 in DBA1 female mice fed either the AIN76 diet or the same diet fortified with 5% lyophilized PM (n=19-20/group. Ten mice/group were immunized with 100 μg bovine collagen type II on day 42 of the protocol, followed by 50 μg lipopolysaccharides on day 62, and euthanized on day 73-74. Cytokines were measured by ELISA.Results:Compared to baseline diet, PM had: no protective effect from CIA since all collagen-immunized mice developed severe edema, bone erosion, and mononuclear cell infiltration in paws. In mice with and those without CIA, feeding a PM-fortified diet resulted in higher percent of body fat than feeding the baseline diet (p<0.05. After CIA induction, PM provided the followingFunctional Foods in Health and Disease 2011; 9:279-296beneficial effects: (a a smaller reduction in lean mass and absolute thymus weight; (b a higher fat mass loss; and (c lower plasma TNF-α levels (p <0.05. PM-fortification did not alter plasma IL-6 and sICAM1 regardless of CIA status; but it increased in vitro IL-6 secretion by mitogen-treated spleen cells.Conclusion:Our data suggest that PM may reduce plasma TNF-α, attenuate lean mass loss and thymus atrophy associated with arthritis, and protect spleen cell function assessed by IL-6 secretion. However, PM-fortification did not attenuate overall CIA pathogenesis which may be due to lack of effect on plasma IL-6. Decreased TNF-α without alterations in IL-6 may reduce the risk of other conditions associated with chronic inflammation such as cardiovascular disease.

  5. Polypores on Spruce in Northeast China

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Poroid species of wood-inhabiting fungi growing on spruce (Picea koraiensis Nakai or Picea yezoensis (Sieb. & Zucc.) Carriere) in Northeast China were investigated during 1993-2002, and 71 species were recorded from these trees or their wood. Skeletocutis lilacina A. David & Jean Keller and Skeletocutis papyracea A. David are new to China. Fomitopsis pinicola (Sw.:Fr.) P. Karst., Onnia leporina (Fr.) H. Jahn, Perenniporia subacida (Peck) Donk, Phaeolus sckweinitzii (Fr.:Fr.) Pat., Phellinidium sulphuras...

  6. Epigenetic’s role in fish pigmentation

    Directory of Open Access Journals (Sweden)

    Laura Cal Delgado

    2014-04-01

    Full Text Available The agouti coat colour gene encodes a paracrine signalling molecule whose differential expression produces the characteristic dorsal-ventral pigment pattern observed in most mammals. We have recently demonstrated that this well-characterised mechanism from mammals also applies to fish with their much more complex pigment patterns. However, the developmental mechanism through which agouti acts to establish these colour differences remains unclear. The present study was undertaken to explore the molecular mechanisms that regulate agouti gene expression by in-vivo functional characterization of the agouti promoter and identification of possible putative regulatory elements that govern basal promoter activity. Specifically, the investigation was focused on the occurrence and role of CpG dinucleotides methylation in the agouti putative promoter sequence and on a possible epigenetic level of regulation of agouti expression. We report here expression analyses of eGFP expression from transgenic zebrafish containing an 8kb-agouti-Tol2-eGFP construct. eGFP expression was specifically found in the brain area and neural tube of Tol2 transposon vector transgenic embryos. Computer-based analysis revealed a putative CpG island immediately proximal to the translation start site. Global inhibition of methylation with 5-aza-2'-deoxycytidine promoted agouti production in association with decreasing CpG methylation. Taken together, these data identify a contributory role for DNA methylation in regulating agouti expression in zebrafish embryogenesis.

  7. 山羊Agouti基因第1内含子T128缺失在中国主要地方山羊品种中的变异%Study on Genetic Diversity of T128 del in Agouti Gene Intron 1 in Chinese Main Indigenous Goat Breeds

    Institute of Scientific and Technical Information of China (English)

    唐春娟; 李祥龙; 周荣艳; 李兰会; 冯付军; 李东锋; 王建涛

    2009-01-01

    Agouti基因在哺乳动物毛色形成过程中扮演着很重要的角色,通过对山羊Agouti基因序列测定发现第1内含子T128缺失位点,利用PCR-RFLP技术检测该位点在国内10个山羊品种中的多态性,并将其与毛色进行相关性分析.结果表明,T128位点存在2个等位基因A(不缺失)和B(缺失),产生3种基因型AA、AB和BB,其中AB基因型在白色山羊品种中占优势(76.14%),AA基因型在棕褐色山羊品种中频率较高(77.41%),BB基因型是黑色山羊品种的优势基因型(87.92%),推测该位点可能在山羊毛色形成过程中发挥一定作用.T128缺失位点在10个山羊品种的平均期望杂合度仅为0.471 8,基因流为0.319 0,遗传分化系数为0.439 3,表明这10个山羊群体间遗传分化程度较低,遗传多样性相对贫乏.

  8. Dorsoventral patterning of the mouse coat by Tbx15.

    OpenAIRE

    Candille, Sophie I.; Van Raamsdonk, Catherine D.; Changyou Chen; Sanne Kuijper; Yanru Chen-Tsai; Andreas Russ; Frits Meijlink; Barsh, Gregory S.

    2004-01-01

    Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (de(H)), affects dorsoventral skin characteristics, especially those under control of the Agouti gene. Mice carrying the Agouti allele black-and-tan (a(t)) normally have a sharp boundary between dorsal black hair and yellow ventral hair; the de(H) mutati...

  9. Genetic polymorphism of adult reindeer coat colour in a herding cooperative in Finnish Lapland

    OpenAIRE

    Jean J. Lauvergne; Mauri Nieminen

    2011-01-01

    In a random sample of 188 adult reindeer belonging to a reindeer herding cooperative in Finnish Lapland, the following coat colour mutants were identified: Abf at the locus Agouti (A), kalppinokka (WNk) at the locus White Nose (WN) and white at the locus W (White). Coefficients of coat colour phenotypic polymorphism K were estimated, in order to quantify this genetic polymorphism. Estimations of K were 12.8% for the locus A (Agouti), 5.1% for the locus WN (White Nose), and 7.5% for the locus ...

  10. New mammalian records in the Parque Nacional Cerros de Amotape, northwestern Peru

    Directory of Open Access Journals (Sweden)

    Cindy M. Hurtado

    2015-04-01

    Full Text Available The Pacific Tropical Rainforest and Equatorial Dry Forest are found only in southern Ecuador and northern Peru, and are among the most poorly known ecosystems of South America. Even though these forests are protected in Parque Nacional Cerros de Amotape (PNCA, they are threatened by fragmentation because of farming and agriculture. The aim of this study was to determine the medium and large mammalian species richness, using transect census, camera trapping, and specimen bone collection. Nine transects were established and 21 camera trap stations were placed along 16 km2 in three localities of PNCA, from August 2012 to April 2013. Total sampling effort was 215 km of transects and 4077 camera-days. We documented 22 species; including 17 with camera trapping, 11 with transect census, and 10 with specimen collection.  Camera traps were the most effective method, and four species (Dasyprocta punctata, Cuniculus paca, Leopardus wiedii and Puma concolor were documented only with this method. This comprised the first Peruvian record for Dasyprocta punctata, and the first record for the western slope of the Peruvian Andes for Cuniculus paca. Also, both specimen collections and sightings confirm the presence of Potos flavus, first record in the western slope of the Peruvian Andes. Panthera onca, Tremarctos ornatus and Saimiri sciureus are considered locally extinct, while several species are in need of further research. We highlight the importance of the high diversity of this rainforests and encourage local authorities to give the area the highest priority in conservation.

  11. Presença de anticorpos da classe IgM de Leptospira interrogans em animais silvestres do Estado do Tocantins, 2002 Presence of IgM antibodies for Leptospira interrogans in wild animals from Tocantins State, 2002

    Directory of Open Access Journals (Sweden)

    Milton Formiga de Souza Júnior

    2006-06-01

    Full Text Available Quatrocentos e vinte e sete amostras de soro provenientes de animais silvestres foram testadas frente a 18 sorovariedades de Leptospira interrogans. De 286 amostras de Cebus apella, 46 (16,1% foram positivas para as sorovariedades pomona, brasiliensis, mini, swajizak, grippothyphosa, sarmin, fluminense, autumnalis, hebdomadis, guaratuba, javanica e icterohaemorhagiae. Das 82 de Alouatta caraya, 2 (2,4% foram positivas para as sorovariedades mangus e fluminense. Das 31 de Nasua nasua, 4 (12,9% foram positivas para as sorovariedades fluminense e javanica. Das 10 amostras de Cerdocyon thous, 2 (20% foram positivas para as sorovariedades fluminense e brasiliensis. Sete de Dasyprocta sp, 6 de Tamandua tetradactila e 5 de Euphractus sexcintus não apresentaram reatividade.Four hundred and twenty-seven serum samples of wild animals were tested against 18 serovars of Leptospira interrogans. Of 286 samples of Cebus apella, 46 (16.1% were positive for the serovars pomona, brasiliensis, mini, swajizak, grippotyphosa, sarmin, fluminense, autumnalis, hebdomadis, guaratuba, javanica and icterohaemorrhagiae. Of 82 samples of Alouatta caraya, 2 (2.4% were positive for the serovars mangus and fluminense. Of 31 samples of Nasua nasua, 4 (12.9% were positive for the serovars fluminense and javanica, and of 10 samples of Cerdocyon thous, 2 (20 % were positive for the serovars fluminense and brasiliensis. Seven samples of Dasyprocta sp, 6 of Tamandua tetradactyla and 5 of Euphractus sexcintus did not present reactivity.

  12. Adaptive variation in beach mice produced by two interacting pigmentation genes.

    Directory of Open Access Journals (Sweden)

    Cynthia C Steiner

    2007-09-01

    Full Text Available Little is known about the genetic basis of ecologically important morphological variation such as the diverse color patterns of mammals. Here we identify genetic changes contributing to an adaptive difference in color pattern between two subspecies of oldfield mice (Peromyscus polionotus. One mainland subspecies has a cryptic dark brown dorsal coat, while a younger beach-dwelling subspecies has a lighter coat produced by natural selection for camouflage on pale coastal sand dunes. Using genome-wide linkage mapping, we identified three chromosomal regions (two of major and one of minor effect associated with differences in pigmentation traits. Two candidate genes, the melanocortin-1 receptor (Mc1r and its antagonist, the Agouti signaling protein (Agouti, map to independent regions that together are responsible for most of the difference in pigmentation between subspecies. A derived mutation in the coding region of Mc1r, rather than change in its expression level, contributes to light pigmentation. Conversely, beach mice have a derived increase in Agouti mRNA expression but no changes in protein sequence. These two genes also interact epistatically: the phenotypic effects of Mc1r are visible only in genetic backgrounds containing the derived Agouti allele. These results demonstrate that cryptic coloration can be based largely on a few interacting genes of major effect.

  13. Molecular mechanism of agonism and inverse agonism in the melanocortin receptors: Zn(2+) as a structural and functional probe

    DEFF Research Database (Denmark)

    Holst, Birgitte; Schwartz, Thue W

    2003-01-01

    Among the rhodopsin-like 7TM receptors, the MC receptors are functionally unique because their high constitutive signaling activity is regulated not only by endogenous peptide agonists-MSH peptides-but also by endogenous inverse agonists, namely, the proteins agouti and AGRP. Moreover, the metal...

  14. Central melanocortins regulate the motivation for sucrose reward

    NARCIS (Netherlands)

    Pandit, Rahul; Van Der Zwaal, Esther M.; Luijendijk, Mieneke C M; Brans, Maike A D; Van Rozen, Andrea J.; Oude Ophuis, Ralph J A; Vanderschuren, Louk J M J; Adan, Roger A H; Fleurla, Susanne E.

    2015-01-01

    The role of the melanocortin (MC) system in feeding behavior is well established. Food intake is potently suppressed by central infusion of the MC 3/4 receptor agonist α-melanocyte stimulating hormone (α-MSH), whereas the MC 3/4 receptor inverse-agonist Agouti Related Peptide (AGRP) has the opposite

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

    Science.gov (United States)

    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...

  16. Locked Nucleic Acid-Based In Situ Hybridization Reveals miR-7a as a Hypothalamus-Enriched MicroRNA with a Distinct Expression Pattern

    DEFF Research Database (Denmark)

    Herzer, S; Silahtaroglu, A; Meister, B

    2012-01-01

    , it was shown that miR-7a was preferentially present in small orexigenic neuropeptide Y (NPY)/agouti-related protein (AgRP)-containing-neurons located in the ventromedial aspect of the arcuate nucleus, but not in large pro-opiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART...

  17. Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice.

    Directory of Open Access Journals (Sweden)

    Marnie E Blewitt

    2006-04-01

    Full Text Available There is increasing evidence in both plants and animals that epigenetic marks are not always cleared between generations. Incomplete erasure at genes associated with a measurable phenotype results in unusual patterns of inheritance from one generation to the next, termed transgenerational epigenetic inheritance. The Agouti viable yellow (A(vy allele is the best-studied example of this phenomenon in mice. The A(vy allele is the result of a retrotransposon insertion upstream of the Agouti gene. Expression at this locus is controlled by the long terminal repeat (LTR of the retrotransposon, and expression results in a yellow coat and correlates with hypomethylation of the LTR. Isogenic mice display variable expressivity, resulting in mice with a range of coat colours, from yellow through to agouti. Agouti mice have a methylated LTR. The locus displays epigenetic inheritance following maternal but not paternal transmission; yellow mothers produce more yellow offspring than agouti mothers. We have analysed the DNA methylation in mature gametes, zygotes, and blastocysts and found that the paternally and maternally inherited alleles are treated differently. The paternally inherited allele is demethylated rapidly, and the maternal allele is demethylated more slowly, in a manner similar to that of nonimprinted single-copy genes. Interestingly, following maternal transmission of the allele, there is no DNA methylation in the blastocyst, suggesting that DNA methylation is not the inherited mark. We have independent support for this conclusion from studies that do not involve direct analysis of DNA methylation. Haplo-insufficiency for Mel18, a polycomb group protein, introduces epigenetic inheritance at a paternally derived A(vy allele, and the pedigrees reveal that this occurs after zygotic genome activation and, therefore, despite the rapid demethylation of the locus.

  18. Illustrations and studies in Neotropical Orchidaceae. 6. The Lepanthes guatemalensis group (Pleurothallidinae in Costa Rica

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    Pupulin, Franco

    2014-06-01

    Full Text Available We revise and characterize the group of species close to Lepanthes guatemalensis. The group comprises eight species in Costa Rica. Three new species are described and illustrated. Lepanthes durikäensis is distinguished by the non resupinate flowers, the lateral sepals ovate with the apical tails diverging, the lower lobe of petals lanceolate-subfalcate, up-curved and the pinkish column. Lepanthes leporina is recognized by the resupinate flowers with yellow sepals, faintly suffused with red, the petals violet, the lip orange, the bifid synsepal with the apices of the lateral sepals not forming tails, the lateral sepals subequal to the dorsal sepal, the petals markedly convex with the upper lobe elliptic-lanceolate and the lobes of the lip connivent at apex. Lepanthes sanctiorum is characterized by the small plants less than 1.1 cm tall, the short peduncle less than 10 mm long, the petals as wide as the lip length and the blades of the lip distinctly diverging at apex. All the species are described and illustrated on the basis of Costa Rican material. A key to the species of the group is provided.Revisamos y caracterizamos el grupo de especies cercanas a Lepanthes guatemalensis. El grupo está compuesto por ocho especies en Costa Rica. Se describen e ilustran tres especies nuevas. Lepanthes durikäensis se caracteriza por las flores no resupinadas, los sépalos laterales ovados, con las colas apicales divergentes, el lóbulo inferior de los pétalos lanceolado-subfalcado, con curvatura hacia arriba y la columna rosada. Lepanthes leporina es reconocida por las flores resupinadas, los sépalos amarillos y ligeramente teñidos de rojo, los pétalos violeta, el labelo naranja, el sinsépalo bífido con los ápices de los sépalos laterales que no forman colas, los sépalos laterales subiguales al sépalo dorsal, los pétalos marcadamente convexo con el lóbulo superior elíptico-lanceolado y los lóbulos del labelo conniventes en el ápice. Lepanthes

  19. Infecções experimentaes na Leishmaniose visceral americana Experimental infections in american visceral leishmaniasis

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    Aristides Marques da Cunha

    1938-01-01

    Leishmaniae being located mainly in the mucous membrane, in infiltration cells located amongst Lieberkuehn's glands and some parasited macrophages could also be observed in the sub-mucosa. Mice as well as the rodents Dasyprocta agouti and Proechymis oris when inoculated, did not become infeced. From the exposed we may conclude that the experimental infections obtained, present a complete analogy with those described in the Mediterrean Kala-azar. On the other hand, the sero-agglutination test, as shown by us in a previous paper, allows no distinction of the species of Leishmania, as all the strains when recently isolated, have the same antigenic constitution which later on undergoes modifications when the Leishmaniae are preserved in culture for a long time. Thus, we feel authorized to conclude that the agent of the visceral american leishmaniasis is identical with L. infantum.

  20. Arborescent palm seed morphology and seedling distribution.

    Science.gov (United States)

    Salm, Rodolfo

    2005-11-01

    This study examines how the seed morphology of two large arborescent palms, Attalea maripa (Aubl.) Mart. and Astrocaryum aculeatum G. Mey, may affect their seed shadow in a seasonally dry Amazonian forest. In addition to being smaller and produced in larger numbers than those of A. aculeatum, A. maripa seeds also presented a substantially lower amount of nutritional reserves available for the embryo. However, A. maripa seedlings were found in much higher numbers than those of A. aculeatum. The results suggest that, within the spatial scale considered, the seed rain of A. maripa is more restricted to the area surrounding around reproductive conspecifics than that of A. aculeatum. Furthermore, in comparison with those of A. aculeatum, the smaller seeds of A. maripa might be less attractive to scatterhoarding rodents (e.g. Dasyprocta aguti). The pattern observed emphasizes the importance of scatterhoarding rodents as dispersers of large-seeded plant species in Neotropical forests. PMID:16532195

  1. Notas sôbre a evolução do virus vacínico em animais silvestres da fauna brasileira

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    Cicero Alves Moreira

    1956-06-01

    Full Text Available A note on the evolution of cow-pox virus in wild animals of Brazilian fauna. We have tried the sensibility of wild animals of Brazilian fauna to the cow-pox virus. The following specimens were submitted to experiences: Procyon cancrivorus, Hydrochoerus capybara, Cavea aperea, Coendu villosus, Didelphis aurita, Bradypus tridactylus, Euphractus sexcintus, Tamandua tetradactylus, Nasua narica, Dasyprocta aguti and Testudo tabulata. In all these animals, - excepting Bradypus tridactylus - we have obtained an infection with incubation (five days, aspect and duration similar to cow-pox of the laboratorial animals (calf and rabbit. In the Bradypus tridactylus howewer, the incubation was very long. Only after 30 days of inoculation we verified the infection with the formation of vesiculae and postulae.

  2. Composição e abundância relativa dos mamíferos de médio e grande porte no Parque Estadual do Turvo, Rio Grande do Sul, Brasil Composition and relative abundance of the medium-large ized mammals of Turvo State Park, Rio Grande do Sul, Brazil

    OpenAIRE

    Carlos B. Kasper; Fábio D. Mazim; José B. G. Soares; Tadeu G. de Oliveira; Marta E. Fabián

    2007-01-01

    Entre janeiro de 2005 e dezembro de 2006 foram realizados estudos sobre a composição e abundância relativa dos mamíferos de médio e grande porte do Parque Estadual do Turvo. Para tanto, foram utilizados registros de armadilhas fotográficas além de visualizações e dados sobre presença e ausência de pegadas ao longo de transectos pré-determinados. No total foram registradas 29 espécies de mamíferos de médio e grande porte, das quais Dasyprocta azarae Lichtenstein, 1823 e Sylvilagus brasiliensis...

  3. Fatty acids composition of fruits of selected Central European sedges (Carex L. Cyperaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Bogucka-Kocka, A.; Janyszek, M.

    2010-07-01

    Fatty acids in the fruits of 13 sedge species (Ca rex L., Cyperaceae) were analyzed. The oil contents in the fruits of the studied sedges ranged from 3.73 and 46.52%. In the studied fruit oils 14 different fatty acids were identified. The main unsaturated fatty acids were: linoleic, a-linolenic, oleic, oleo palmitic n-7; oleo palmitic n-9, octadecenic, and eicosenoic acids. The following acids were found in the greatest quantities: linoleic, oleic, a-linolenic and palmitic acids. Based on the fatty acid composition, studied taxa can be divided in two groups. The first group (C. flava, C. pseudocyperus, C. riparia, C. leporina) is a very good source of linoleic acid. The second group, including the remaining species, is a good source of a-linolenic acid. The highest oleic acid contents were observed in C. vulpina. The studied material has shown a low concentration of saturated fatty acids, among which palmitic acid was the main one.Results of the analyses allow for the inclusion of the studied species among plants whose fruits are characterized by a high content of unsaturated fatty acids. (Author)

  4. Genetic polymorphism of adult reindeer coat colour in a herding cooperative in Finnish Lapland

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    Jean J. Lauvergne

    2011-04-01

    Full Text Available In a random sample of 188 adult reindeer belonging to a reindeer herding cooperative in Finnish Lapland, the following coat colour mutants were identified: Abf at the locus Agouti (A, kalppinokka (WNk at the locus White Nose (WN and white at the locus W (White. Coefficients of coat colour phenotypic polymorphism K were estimated, in order to quantify this genetic polymorphism. Estimations of K were 12.8% for the locus A (Agouti, 5.1% for the locus WN (White Nose, and 7.5% for the locus W (White. This polymorphism results probably from a change in fitness coefficient of genotypes carrying colour mutants following domestication in a random mating context which has not yet been proved.

  5. The Melanocortinergic Pathway Is Rapidly Recruited by Emotional Stress and Contributes to Stress-Induced Anorexia and Anxiety-Like Behavior

    OpenAIRE

    Liu, Jing; Garza, Jacob C.; Truong, Ha V.; Henschel, John; Zhang, Wei; Lu, Xin-Yun

    2007-01-01

    Neurons producing melanocortin receptor agonist, α-MSH derived from proopiomelanocortin, and antagonist, agouti-related protein, are known to be sensitive to metabolic stress such as food deprivation and glucoprivation. However, how these neurons respond to emotional/psychological stress remained to be elucidated. We report here that acute emotional stressors, i.e. restraint and forced swim, evoked mRNA expression of c-fos, a neuronal activation marker, in a high percentage of proopiomelanoco...

  6. Inheritance of a Parotid Secretory Protein in Mice and Its Use in Determining Salivary Amylase Quantitative Variants

    OpenAIRE

    Owerbach, David; Hjorth, J. Peter

    1980-01-01

    Among inbred strains of mice, a major protein, PSP, produced and secreted by the parotid glands, shows variation in electrophoretic mobility and in the peptides produced by cyanogen bromide treatment. This variation is inherited as a single Mendelian factor with two alleles showing co-dominant expression. In genetic crosses, it segregates independently from the amylase complex and is closely linked to the agouti locus on chromosome 2. The protein ratios between amylase and PSP in saliva, obta...

  7. Pleiotropy in the melanocortin system, coloration and behavioural syndromes.

    OpenAIRE

    Ducrest A.L.; Keller L; Roulin A.

    2008-01-01

    In vertebrates, melanin-based coloration is often associated with variation in physiological and behavioural traits. We propose that this association stems from pleiotropic effects of the genes regulating the synthesis of brown to black eumelanin. The most important regulators are the melanocortin 1 receptor and its ligands, the melanocortin agonists and the agouti-signalling protein antagonist. On the basis of the physiological and behavioural functions of the melanocortins, we predict five ...

  8. Linkage and Segregation Analysis of Black and Brindle Coat Color in Domestic Dogs

    OpenAIRE

    Kerns, Julie A.; Cargill, Edward J; Clark, Leigh Anne; Candille, Sophie I.; Berryere, Tom G.; Olivier, Michael; Lust, George; Todhunter, Rory J.; Schmutz, Sheila M.; Murphy, Keith E; Barsh, Gregory S

    2007-01-01

    Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red–yellow pheomelanin vs. black–brown eumelanin. However, in domestic dogs, historical studies based on pedigree and segregation analysis have suggested that the pigment type-switching sy...

  9. Melanocortin-1 receptor-mediated signalling pathways activated by NDP-MSH and HBD3 ligands

    OpenAIRE

    Beaumont, Kimberley A.; Smit, Darren J.; Liu, Yan Yan; Chai, Eric; Patel, Mira P.; Millhauser, Glenn L.; Smith, Jennifer J.; Alewood, Paul F.; Sturm, Richard A.

    2012-01-01

    Binding of melanocortin peptide agonists to the melanocortin-1 receptor of melanocytes results in eumelanin production, whereas binding of the agouti signalling protein inverse agonist results in pheomelanin synthesis. Recently, a novel melanocortin-1 receptor ligand was reported. A β-defensin gene mutation was found to beresponsible for black coat colour in domestic dogs. Notably, the human equivalent, β-defensin 3, was found to bind with high affinity to the melanocortin-1 receptor; however...

  10. Starvation after AgRP neuron ablation is independent of melanocortin signaling

    OpenAIRE

    Wu, Qi; Howell, Maureen P.; Cowley, Michael A.; Palmiter, Richard D.

    2008-01-01

    Ablation of inhibitory agouti-related protein (AgRP)-expressing neurons in the arcuate nucleus that also synthesize γ-amino-butyric acid (GABA) and neuropeptide Y in adult mice leads to starvation within 1 week. The removal of inhibition from the AgRP neurons onto neighboring proopiomelanocortin neurons and their common postsynaptic neurons is predicted to stimulate melanocortin signaling, which is known to inhibit appetite. To examine the importance of uncontrolled melanocortin signaling in ...

  11. Effects of Leptin and Melanocortin Signaling Interactions on Pubertal Development and Reproduction

    OpenAIRE

    Israel, Davelene D.; Sheffer-Babila, Sharone; de Luca, Carl; Jo, Young-Hwan; Liu, Shun Mei; Xia, Qiu; Spergel, Daniel J.; Dun, Siok L.; Dun, Nae J.; Chua, Streamson C.

    2012-01-01

    Leptin and melanocortin signaling control ingestive behavior, energy balance, and substrate utilization, but only leptin signaling defects cause hypothalamic hypogonadism and infertility. Although GnRH neurons do not express leptin receptors, leptin influences GnRH neuron activity via regulation of immediate downstream mediators including the neuropeptides neuropeptide Y and the melanocortin agonist and antagonist, α-MSH, agouti-related peptide, respectively. Here we show that modulation of m...

  12. Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions*

    OpenAIRE

    Hou, Wei-kun; Meng, Lie-su; Zheng, Fang; Wen, Yu-rong; Zhu, Wen-Hua; Jiang, Cong-shan; He, Xiao-Jing; Zhou, Yan; Lu, She-Min

    2011-01-01

    Objective: This study was carried out to test the effects of methotrexate (MTX) and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats. Methods: Inbred dark agouti (DA) rats were induced by a single subcutaneous injection of pristane, and then treated with MTX or BSO. Arthritis severity was evaluated macroscopically and microscopically. Plasma nitric oxide (NO) concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-t...

  13. Differential expression of proteoglycans in tissue remodeling and lymphangiogenesis after experimental renal transplantation in rats.

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    Heleen Rienstra

    Full Text Available BACKGROUND: Chronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction. METHODS: Renal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin and chondroitin sulfate proteoglycan (versican expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively expression were (semi- quantitatively analyzed using immunofluorescence. FINDINGS: Arteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso- and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (p<0.01 compared to isografts and non-transplanted controls, which was associated with induced perlecan expression underneath the lymphatic endothelium (p<0.05 and p<0.01 compared to isografts and non-transplanted controls, respectively. Both the magnitude of lymphangiogenesis and perlecan expression correlated with severity of interstitial fibrosis and impaired graft function

  14. The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia

    OpenAIRE

    Dallmann, R; Weyermann, P.; Anklin, C; Boroff, M.; Bray-French, K.; Cardel, B; Courdier-Fruh, I; Deppe, H.; Dubach-Powell, J.; Erb, M.; Haefeli, R H; Henneböhle, M; Herzner, H.; Marks, D. L.; Hufschmid, M

    2011-01-01

    BACKGROUND: Under physiological conditions, the melanocortin system is a crucial part of the complex network regulating food intake and energy expenditure. In pathological states, like cachexia, these two parameters are deregulated, i.e., food intake is decreased and energy expenditure is increased-a vicious combination leading to catabolism. Agouti-related protein (AgRP), the endogenous antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food intake and to reduce energy ...

  15. Adaptive radiation-induced epigenetic alterations mitigated by antioxidants

    OpenAIRE

    Bernal, Autumn J.; Dolinoy, Dana C; Huang, Dale; Skaar, David A.; Weinhouse, Caren; Jirtle, Randy L

    2013-01-01

    Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (Avy) locus in a sex-specific man...

  16. Dorsoventral patterning of the mouse coat by Tbx15.

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    Sophie I Candille

    2004-01-01

    Full Text Available Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (de(H, affects dorsoventral skin characteristics, especially those under control of the Agouti gene. Mice carrying the Agouti allele black-and-tan (a(t normally have a sharp boundary between dorsal black hair and yellow ventral hair; the de(H mutation raises the pigmentation boundary, producing an apparent dorsal-to-ventral transformation. We identify a 216 kb deletion in de(H that removes all but the first exon of the Tbx15 gene, whose embryonic expression in developing mesenchyme correlates with pigmentary and skeletal malformations observed in de(H/de(H animals. Construction of a targeted allele of Tbx15 confirmed that the de(H phenotype was caused by Tbx15 loss of function. Early embryonic expression of Tbx15 in dorsal mesenchyme is complementary to Agouti expression in ventral mesenchyme; in the absence of Tbx15, expression of Agouti in both embryos and postnatal animals is displaced dorsally. Transplantation experiments demonstrate that positional identity of the skin with regard to dorsoventral pigmentation differences is acquired by E12.5, which is shortly after early embryonic expression of Tbx15. Fate-mapping studies show that the dorsoventral pigmentation boundary is not in register with a previously identified dermal cell lineage boundary, but rather with the limb dorsoventral boundary. Embryonic expression of Tbx15 in dorsolateral mesenchyme provides an instructional cue required to establish the future positional identity of dorsal dermis. These findings represent a novel role for T-box gene action in embryonic development, identify a previously unappreciated aspect of dorsoventral patterning that is widely represented in furred mammals, and provide insight into the mechanisms that underlie

  17. Agent-based modeling for the landuse change of hunter-gather societies and the impacts on biodiversity in Guyana

    Science.gov (United States)

    Iwamura, T.; Fragoso, J.; Lambin, E.

    2012-12-01

    The interactions with animals are vital to the Amerindian, indigenous people, of Rupunini savannah-forest in Guyana. Their connections extend from basic energy and protein resource to spiritual bonding through "paring" to a certain animal in the forest. We collected extensive dataset of 23 indigenous communities for 3.5 years, consisting 9900 individuals from 1307 households, as well as animal observation data in 8 transects per communities (47,000 data entries). In this presentation, our research interest is to model the driver of land use change of the indigenous communities and its impacts on the ecosystem in the Rupunini area under global change. Overarching question we would like to answer with this program is to find how and why "tipping-point" from hunting gathering society to the agricultural society occurs in the future. Secondary question is what is the implication of the change to agricultural society in terms of biodiversity and carbon stock in the area, and eventually the well-being of Rupunini people. To answer the questions regarding the society shift in agriculture activities, we built as simulation with Agent-Based Modeling (Multi Agents Simulation). We developed this simulation by using Netlogo, the programming environment specialized for spatially explicit agent-based modeling (ABM). This simulation consists of four different process in the Rupunini landscape; forest succession, animal population growth, hunting of animals, and land clearing for agriculture. All of these processes are carried out by a set of computational unit, called "agents". In this program, there are four types of agents - patches, villages, households, and animals. Here, we describe the impacts of hunting on the biodiversity based on actual demographic data from one village named Crush Water. Animal population within the hunting territory of the village stabilized but Agouti/Paca dominates the landscape with little population of armadillos and peccaries. White-tailed deers

  18. Diversidad de mamíferos terrestres de talla grande y media de una selva subcaducifolia del noreste de Oaxaca, México Diversity of large and medium sized land mammals of a subcaducifolious tropical forest of north eastern of Oaxaca, Mexico

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    Gabriela Pérez-Irineo

    2012-03-01

    Full Text Available El estado de Oaxaca en el sureste de México alberga una biodiversidad extraordinaria. Sin embargo, las actividades humanas han propiciado alteraciones considerables, incluida la disminución de diferentes ambientes naturales, especialmente de los bosques tropicales; por ello es importante documentar la diversidad de estos ambientes, así como su respuesta a las transformaciones antropocéntricas. Este trabajo tiene como objetivo estimar la diversidad de mamíferos terrestres en una selva mediana en el noreste del estado de Oaxaca, México. Se recorrieron 3 senderos para la búsqueda de rastros, captura de organismos, avistamientos y fototrampeo de septiembre de 2007 a agosto de 2008. Se registraron 15 especies de 6 órdenes, 11 familias y 14 géneros, entre ellas 7 nuevas para la región. Las especies más abundantes fueron Nasua narica, Pecari tajacu, Dasyprocta mexicana, Cuniculus paca y Leopardus pardalis. A pesar de presentar un índice de diversidad bajo con respecto a otros estudios comparables, la presencia de especies consideradas en riesgo por la legislación mexicana, como L. pardalis, L. wiedii, Eira barbara y Tamandua mexicana hacen a la zona valiosa para la conservación de la diversidad en la región.The state of Oaxaca, in southeast Mexico is home to an extraordinary biodiversity. But human activities have led to significant changes, including reduction of different natural habitats, especially tropical forests, so it is important to document the diversity of these environments, and their response to the anthropocentric changes. Therefore, this study aimed to estimate the diversity of terrestrial mammals in a tropical forest in northeastern of the state of Oaxaca, Mexico. Three transects were walked to search for tracks, catches of organisms, sightings, and phototrapping from September 2007 to August 2008. There were recorded 15 species of 6 orders, 11 families, and 14 genera, 7 of this not previously known in the region. The

  19. Comprehensive Assessment of Oxidatively Induced Modifications of DNA in a Rat Model of Human Wilson's Disease.

    Science.gov (United States)

    Yu, Yang; Guerrero, Candace R; Liu, Shuo; Amato, Nicholas J; Sharma, Yogeshwar; Gupta, Sanjeev; Wang, Yinsheng

    2016-03-01

    Defective copper excretion from hepatocytes in Wilson's disease causes accumulation of copper ions with increased generation of reactive oxygen species via the Fenton-type reaction. Here we developed a nanoflow liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry coupled with the isotope-dilution method for the simultaneous quantification of oxidatively induced DNA modifications. This method enabled measurement, in microgram quantities of DNA, of four oxidative stress-induced lesions, including direct ROS-induced purine cyclonucleosides (cPus) and two exocyclic adducts induced by byproducts of lipid peroxidation, i.e. 1,N(6)-etheno-2'-deoxyadenosine (εdA) and 1,N(2)-etheno-2'-deoxyguanosine (εdG). Analysis of liver tissues of Long-Evans Cinnamon rats, which constitute an animal model of human Wilson's disease, and their healthy counterparts [i.e. Long-Evans Agouti rats] showed significantly higher levels of all four DNA lesions in Long-Evans Cinnamon than Long-Evans Agouti rats. Moreover, cPus were present at much higher levels than εdA and εdG lesions. In contrast, the level of 5-hydroxymethyl-2'-deoxycytidine (5-HmdC), an oxidation product of 5-methyl-2'-deoxycytidine (5-mdC), was markedly lower in the liver tissues of Long-Evans Cinnamon than Long-Evans Agouti rats, though no differences were observed for the levels of 5-mdC. In vitro biochemical assay showed that Cu(2+) ions could directly inhibit the activity of Tet enzymes. Together, these results suggest that aberrant copper accumulation may perturb genomic stability by elevating oxidatively induced DNA lesions, and by altering epigenetic pathways of gene regulation.

  20. Anorexia in rats caused by a valine-deficient diet is not ameliorated by systemic ghrelin treatment.

    Science.gov (United States)

    Goto, S; Nagao, K; Bannai, M; Takahashi, M; Nakahara, K; Kangawa, K; Murakami, N

    2010-03-10

    Rodents exhibit aversive behavior toward a diet that lacks at least one of the essential amino acids. We sought to determine whether the particular form of anorexia caused by such diets could be ameliorated by the administration of orexigenic peptides while simultaneously analyzing the neural mechanisms underlying anorexia. Rats were fed a valine-deficient diet, which induced severe anorexia (reducing food consumption by 80%). The severe anorexia was associated with a significant decrease in the cerebrospinal fluid valine concentration and hyper-ghrelinemia. Between 6 and 12 days after initiation of the valine-deficient diet, we injected rats twice daily with valine and/or an orexigenic peptide (ghrelin, neuropeptide Y, or agouti-related protein) either i.p. or i.c.v.. We then measured dietary intake. An i.c.v. valine injection allowed earlier food intake compared with an i.p valine injection and increased the density of c-Fos-positive ependymal cells lining the third ventricle. Whereas an i.c.v. injection of ghrelin or neuropeptide Y increased consumption of the valine-deficient diet, i.p injection of ghrelin or i.c.v. injection of agouti-related protein did not. Following i.c.v. administration of either valine or ghrelin, we did not observe complete recovery of consumption of the valine-deficient diet. This may be due to the ineffectiveness of peripheral ghrelin and central agouti-related protein and/or to conditioned aversion to the valine-deficient diet. Since ghrelin is known to be involved in food anticipatory activities, whether the hyper-ghrelinemia observed in valine-deficient rats play role in foraging behavior other than food intake is the future study to be investigated.

  1. Comprehensive Assessment of Oxidatively Induced Modifications of DNA in a Rat Model of Human Wilson's Disease.

    Science.gov (United States)

    Yu, Yang; Guerrero, Candace R; Liu, Shuo; Amato, Nicholas J; Sharma, Yogeshwar; Gupta, Sanjeev; Wang, Yinsheng

    2016-03-01

    Defective copper excretion from hepatocytes in Wilson's disease causes accumulation of copper ions with increased generation of reactive oxygen species via the Fenton-type reaction. Here we developed a nanoflow liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry coupled with the isotope-dilution method for the simultaneous quantification of oxidatively induced DNA modifications. This method enabled measurement, in microgram quantities of DNA, of four oxidative stress-induced lesions, including direct ROS-induced purine cyclonucleosides (cPus) and two exocyclic adducts induced by byproducts of lipid peroxidation, i.e. 1,N(6)-etheno-2'-deoxyadenosine (εdA) and 1,N(2)-etheno-2'-deoxyguanosine (εdG). Analysis of liver tissues of Long-Evans Cinnamon rats, which constitute an animal model of human Wilson's disease, and their healthy counterparts [i.e. Long-Evans Agouti rats] showed significantly higher levels of all four DNA lesions in Long-Evans Cinnamon than Long-Evans Agouti rats. Moreover, cPus were present at much higher levels than εdA and εdG lesions. In contrast, the level of 5-hydroxymethyl-2'-deoxycytidine (5-HmdC), an oxidation product of 5-methyl-2'-deoxycytidine (5-mdC), was markedly lower in the liver tissues of Long-Evans Cinnamon than Long-Evans Agouti rats, though no differences were observed for the levels of 5-mdC. In vitro biochemical assay showed that Cu(2+) ions could directly inhibit the activity of Tet enzymes. Together, these results suggest that aberrant copper accumulation may perturb genomic stability by elevating oxidatively induced DNA lesions, and by altering epigenetic pathways of gene regulation. PMID:26362317

  2. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    OpenAIRE

    Mayado Andrea; Torres Elisa; Gutierrez-Lopez Maria D; Colado Maria I; O'Shea Esther

    2011-01-01

    Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p.) 96 h before receiving neurotoxic MDMA (12.5 mg/kg, ...

  3. STEAROYL-CoA DESATURASE-1 DEFICIENCY ATTENUATES OBESITY AND INSULIN RESISTANCE IN LEPTIN-RESISTANT OBESE MICE

    OpenAIRE

    Miyazaki, Makoto; Sampath, Harini; Liu, Xueqing; Flowers, Matthew T.; Chu, Kiki; Dobrzyn, Agnieszka; Ntambi, James M.

    2009-01-01

    Obesity and adiposity greatly increase the risk for secondary conditions such as insulin resistance. Mice deficient in the enzyme stearoyl-CoA desaturase-1 (SCD1) are lean and protected from diet-induced obesity and insulin resistance. In order to determine the effect of SCD1 deficiency on various mouse models of obesity, we introduced a global deletion of the Scd1 gene into leptin-deficient ob/ob mice, leptin-resistant Agouti (Ay/a) mice, and high-fat diet-fed obese (DIO) mice. SCD1 deficien...

  4. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    OpenAIRE

    Tadashi Okamura; Xiang Yuan Pei; Ichiro Miyoshi; Yukiko Shimizu; Rieko Takanashi-Yanobu; Yasumasa Mototani; Takao Kanai; Jo Satoh; Noriko Kimura; Noriyuki Kasai

    2013-01-01

    Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose into...

  5. Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse

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    Suto Jun-ichi

    2012-11-01

    Full Text Available Abstract Background Adrenal gland of mice contains a transient zone between the adrenal cortex and the adrenal medulla: the X-zone. There are clear strain differences in terms of X-zone morphology. Nulliparous females of the inbred mouse DDD strain develop adrenal X-zones containing exclusively vacuolated cells, whereas females of the inbred mouse B6 strain develop X-zones containing only non-vacuolated cells. The X-zone vacuolation is a physiologic process associated with the X-zone degeneration and is tightly regulated by genetic factors. Identification of the genetic factors controlling such strain differences should help analyze the X-zone function. In this study, a quantitative trait locus (QTL analysis for the extent of X-zone vacuolation was performed for two types of F2 female mice: F2Ay mice (F2 mice with the Ay allele and F2 non-Ay mice (F2 mice without the Ay allele. These were produced by crossing B6 females and DDD.Cg-Ay males. DDD.Cg-Ay is a congenic mouse strain for the Ay allele at the agouti locus and is used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested. The Ay allele is dominant and homozygous lethal; therefore, living Ay mice are invariably heterozygotes. Results Single QTL scans identified significant QTLs on chromosomes 1, 2, 6, and X for F2 non-Ay mice, and on chromosomes 2, 6, and 12 for F2Ay mice. The QTL on chromosome 2 was considered to be because of the agouti locus, which has been suggested to be associated with X-zone vacuolation. A significant QTL that interacted with the agouti locus was identified on chromosome 8. Conclusions The extent of X-zone vacuolation in DDD females was controlled by multiple genes with complex interactions. The murine X-zone is considered analogous structure to the human fetal zone. Therefore, the results of this study will aid in understanding function of not only of the X-zone but also of the human fetal zone

  6. Genetic analysis of the cat population of north and south of cali, colombia

    OpenAIRE

    PEÑA-CRUZ, Andrés F.; SANDOVAL ARANGO, Stephania; Angie PATIÑO MONTOYA; BEDOYA, Mailyn; RODRÍGUEZ ORTIZ, Alejandra; ORJUELA VASQUEZ, Juan; Ortega, Alejandra; F. LÓPEZ, Juan; Edward MOLINA HENAO; Angélica GUZMÁN; GIL, Julian; Heiber CÁRDENAS HENAO

    2014-01-01

    The coat genetic markers and skeleton abnormalities have allowed characterize the profile from more than 400 domestic cat populations around the world. 15 years ago, that profile was established in the city of Cali (Colombia). In this study it was determined if north and south of the city are subpopulations and it was compared the total profile against past study. A decrease in allele frequency of a (non-agouti) and d (dilution) was found, but an increase of five alleles was found, especially...

  7. Regulation of eumelanin / pheomelanin synthesis and visible pigmentation in melanocytes by ligands of the melanocortin 1 receptor

    OpenAIRE

    Le Pape, Elodie; Wakamatsu, Kazumasa; Ito, Shosuke; Wolber, Rainer; Hearing, Vincent J.

    2008-01-01

    The production of melanin in the hair and skin is tightly regulated by the melanocortin 1 receptor (MC1R) whose activation is controlled by 2 secreted ligands, α-melanocyte stimulating hormone (αMSH) and agouti signal protein (ASP). Since melanin is extremely stable, lasting years in biological tissues, the mechanism underlying the relatively rapid decrease in visible pigmentation elicited by ASP is of obvious interest. In this study, the effects of ASP and αMSH on the regulation of melanin s...

  8. Role of hypothalamic melanocortin system in adaptation of food intake to food protein increase in mice.

    OpenAIRE

    Pillot, Bruno; Duraffourd, Céline; Bégeot, Martine; Joly, Aurélie; Luquet, Serge; Houberdon, Isabelle; Naville, Danielle; Vigier, Michèle; Gautier-Stein, Amandine; Magnan, Christophe; Mithieux, Gilles

    2011-01-01

    The hypothalamic melanocortin system--the melanocortin receptor of type 4 (MC4R) and its ligands: α-melanin-stimulating hormone (α-MSH, agonist, inducing hypophagia), and agouti-related protein (AgRP, antagonist, inducing hyperphagia)--is considered to play a central role in the control of food intake. We tested its implication in the mediation of the hunger-curbing effects of protein-enriched diets (PED) in mice. Whereas there was a 20% decrease in food intake in mice fed on the PED, compare...

  9. Regulation of Prolactin in Mice with Altered Hypothalamic Melanocortin Activity

    OpenAIRE

    Dutia, Roxanne; Kim, Andrea J.; Mosharov, Eugene; Savontaus, Eriika; Chua, Streamson C.; Wardlaw, Sharon L.

    2012-01-01

    This study used two mouse models with genetic manipulation of the melanocortin system to investigate prolactin regulation. Mice with overexpression of the melanocortin receptor (MC-R) agonist, α-melanocyte-stimulating hormone (Tg-MSH) or deletion of the MC-R antagonist agouti-related protein (AgRP KO) were studied. Male Tg-MSH mice had lower blood prolactin levels at baseline (2.9±0.3 vs 4.7±0.7 ng/ml) and after restraint stress(68 ±6.5 vs 117±22 ng/ml) versus WT (p

  10. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease.

    OpenAIRE

    Li, Y; Togashi, Y; S. Sato; Emoto, T; J. H. Kang; TAKEICHI N.; Kobayashi, H; Y. Kojima; Une, Y.; Uchino, J

    1991-01-01

    Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decr...

  11. [Wildlife damage mitigation in agricultural crops in a Bolivian montane forest].

    Science.gov (United States)

    Perez, Eddy; Pacheco, Luis F

    2014-12-01

    Wildlife is often blamed for causing damage to human activities, including agricultural practices and the result may be a conflict between human interests and species conservation. A formal assessment of the magnitude of damage is necessary to adequately conduct management practices and an assessment of the efficiency of different management practices is necessary to enable managers to mitigate the conflict with rural people. This study was carried out to evaluate the effectiveness of agricultural management practices and controlled hunting in reducing damage to subsistence annual crops at the Cotapata National Park and Natural Area of Integrated Management. The design included seven fields with modified agricultural practices, four fields subjected to control hunting, and five fields held as controls. We registered cultivar type, density, frequency of visiting species to the field, crops lost to wildlife, species responsible for damage, and crop biomass. Most frequent species in the fields were Dasyprocta punctata and Dasypus novemcinctus. Hunted plots were visited 1.6 times more frequently than agriculturally managed plots. Crop lost to wildlife averaged 7.28% at agriculturally managed plots, 4.59% in plots subjected to hunting, and 27.61% in control plots. Species mainly responsible for damage were Pecari tajacu, D. punctata, and Sapajus apella. We concluded that both management strategies were effective to reduce damage by >50% as compared to unmanaged crop plots.

  12. Polyspecific associations between squirrel monkeys (Saimiri sciureus) and other primates in eastern Amazonia.

    Science.gov (United States)

    Pinheiro, Tatyana; Ferrari, Stephen F; Lopes, Maria Aparecida

    2011-11-01

    One of the most common types of polyspecific association observed in Neotropical primate communities is that between squirrel monkeys (Saimiri) and capuchins (Cebus). The present study focused on association patterns in two Saimiri sciureus groups in eastern Brazilian Amazonia, between March and October, 2009. The associations were analyzed in terms of the species involved, the degree of association, and niche breadth and overlap. The study involved two S. sciureus groups (B4 and GI) on the right and left bank of the Tocantins River, respectively, within the area of the Tucuruí reservoir in southeastern Pará. Relations between species were classified as associations (individuals within 50 m and moving in the same direction), and encounters (individuals within 50 m and no coordinated movement). Group B4 was in association with Cebus apella during 100% of monitoring, and with Chiropotes satanas in 20.2%. By contrast, Group GI associated with Cebus 54.8% of the time, and with Chiropotes utahickae 2.5%. Encounters with Alouatta belzebul and Saguinus niger were recorded at both sites, with Aotus azarae and Dasyprocta prymnolopha at B4, and with Callicebus moloch, Dasyproct aleporina, Mazama gouazoubira, and Nasua nasua at GI. Overall, Saimiri had a broader niche than Cebus in terms of vertical spacing and diet, but not for substrate use. This pattern did not appear to be affected by association. While group GI spent significantly (P foraging patterns at the two sites, and the varying potential benefits of association for Saimiri. PMID:21809365

  13. Hunting and use of terrestrial fauna used by Caiçaras from the Atlantic Forest coast (Brazil

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    Alves Rômulo RN

    2009-11-01

    Full Text Available Abstract Background The Brazilian Atlantic Forest is considered one of the hotspots for conservation, comprising remnants of rain forest along the eastern Brazilian coast. Its native inhabitants in the Southeastern coast include the Caiçaras (descendants from Amerindians and European colonizers, with a deep knowledge on the natural resources used for their livelihood. Methods We studied the use of the terrestrial fauna in three Caiçara communities, through open-ended interviews with 116 native residents. Data were checked through systematic observations and collection of zoological material. Results The dependence on the terrestrial fauna by Caiçaras is especially for food and medicine. The main species used are Didelphis spp., Dasyprocta azarae, Dasypus novemcinctus, and small birds (several species of Turdidae. Contrasting with a high dependency on terrestrial fauna resources by native Amazonians, the Caiçaras do not show a constant dependency on these resources. Nevertheless, the occasional hunting of native animals represents a complimentary source of animal protein. Conclusion Indigenous or local knowledge on native resources is important in order to promote local development in a sustainable way, and can help to conserve biodiversity, particularly if the resource is sporadically used and not commercially exploited.

  14. Monitoring the status and trends of tropical forest terrestrial vertebrate communities from camera trap data: a tool for conservation.

    Science.gov (United States)

    Ahumada, Jorge A; Hurtado, Johanna; Lizcano, Diego

    2013-01-01

    Reducing the loss of biodiversity is key to ensure the future well being of the planet. Indicators to measure the state of biodiversity should come from primary data that are collected using consistent field methods across several sites, longitudinal, and derived using sound statistical methods that correct for observation/detection bias. In this paper we analyze camera trap data collected between 2008 and 2012 at a site in Costa Rica (Volcan Barva transect) as part of an ongoing tropical forest global monitoring network (Tropical Ecology Assessment and Monitoring Network). We estimated occupancy dynamics for 13 species of mammals, using a hierarchical modeling approach. We calculated detection-corrected species richness and the Wildlife Picture Index, a promising new indicator derived from camera trap data that measures changes in biodiversity from the occupancy estimates of individual species. Our results show that 3 out of 13 species showed significant declines in occupancy over 5 years (lowland paca, Central American agouti, nine-banded armadillo). We hypothesize that hunting, competition and/or increased predation for paca and agouti might explain these patterns. Species richness and the Wildlife Picture Index are relatively stable at the site, but small herbivores that are hunted showed a decline in diversity of about 25%. We demonstrate the usefulness of longitudinal camera trap deployments coupled with modern statistical methods and advocate for the use of this approach in monitoring and developing global and national indicators for biodiversity change. PMID:24023898

  15. Monitoring the status and trends of tropical forest terrestrial vertebrate communities from camera trap data: a tool for conservation.

    Directory of Open Access Journals (Sweden)

    Jorge A Ahumada

    Full Text Available Reducing the loss of biodiversity is key to ensure the future well being of the planet. Indicators to measure the state of biodiversity should come from primary data that are collected using consistent field methods across several sites, longitudinal, and derived using sound statistical methods that correct for observation/detection bias. In this paper we analyze camera trap data collected between 2008 and 2012 at a site in Costa Rica (Volcan Barva transect as part of an ongoing tropical forest global monitoring network (Tropical Ecology Assessment and Monitoring Network. We estimated occupancy dynamics for 13 species of mammals, using a hierarchical modeling approach. We calculated detection-corrected species richness and the Wildlife Picture Index, a promising new indicator derived from camera trap data that measures changes in biodiversity from the occupancy estimates of individual species. Our results show that 3 out of 13 species showed significant declines in occupancy over 5 years (lowland paca, Central American agouti, nine-banded armadillo. We hypothesize that hunting, competition and/or increased predation for paca and agouti might explain these patterns. Species richness and the Wildlife Picture Index are relatively stable at the site, but small herbivores that are hunted showed a decline in diversity of about 25%. We demonstrate the usefulness of longitudinal camera trap deployments coupled with modern statistical methods and advocate for the use of this approach in monitoring and developing global and national indicators for biodiversity change.

  16. Behind melanocortin antagonist overexpression in the zebrafish brain: A behavioral and transcriptomic approach.

    Science.gov (United States)

    Guillot, Raúl; Cortés, Raúl; Navarro, Sandra; Mischitelli, Morena; García-Herranz, Víctor; Sánchez, Elisa; Cal, Laura; Navarro, Juan Carlos; Míguez, Jesús M; Afanasyev, Sergey; Krasnov, Aleksei; Cone, Roger D; Rotllant, Josep; Cerdá-Reverter, Jose Miguel

    2016-06-01

    Melanocortin signaling is regulated by the binding of naturally occurring antagonists, agouti-signaling protein (ASIP) and agouti-related protein (AGRP) that compete with melanocortin peptides by binding to melanocortin receptors to regulate energy balance and growth. Using a transgenic model overexpressing ASIP, we studied the involvement of melanocortin system in the feeding behaviour, growth and stress response of zebrafish. Our data demonstrate that ASIP overexpression results in enhanced growth but not obesity. The differential growth is explained by increased food intake and feeding efficiency mediated by a differential sensitivity of the satiety system that seems to involve the cocaine- and amphetamine- related transcript (CART). Stress response was similar in both genotypes. Brain transcriptome of transgenic (ASIP) vs wild type (WT) fish was compared using microarrays. WT females and males exhibited 255 genes differentially expressed (DEG) but this difference was reduced to 31 after ASIP overexpression. Statistical analysis revealed 1122 DEG when considering only fish genotype but 1066 and 981 DEG when comparing ASIP males or females with their WT counterparts, respectively. Interaction between genotype and sex significantly affected the expression of 97 genes. Several neuronal systems involved in the control of food intake were identified which displayed a differential expression according to the genotype of the fish that unravelling the flow of melanocortinergic information through the central pathways that controls the energy balance. The information provided herein will help to elucidate new central systems involved in control of obesity and should be of invaluable use for sustaining fish production systems. PMID:27156808

  17. Preliminary study on MC1R polymorphism in some cattle breeds raised in Italy

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    C. Renieri

    2011-03-01

    Full Text Available Most of the Western European cattle breeds consist of standardised breeds with a definite coat colour (Renieri et al., 1984. Thus coat colour could be useful to detect genetic markers for cattle breed identification. In cattle the pigmentation is determined by the distribution of two pigments: eu- and pheomelanin, producing brown or black and red to yellow pigmentation respectively. Tyrosinase, the rate-limiting enzyme involved in the synthesis of both melanins, is regulated by the melanocyte stimulating hormone (αMSH. This hormone and several other melanotropic peptides stimulate melanin formation in melanocytes by binding to the melanocortin-1-receptor (MC1R, a G-protein-coupled receptor encoded by the Extension gene (Robbins et al., 1993. In addition, the amounts of eu- and pheomelanin in the melanocyte are controlled by the agouti gene encoding the Agouti Signal Protein (ASP, that acts as an antagonist of MSH signalling through the MC1R, even if its mechanism of action is controversial (Furumura et al., 1998..........

  18. Composição e abundância relativa dos mamíferos de médio e grande porte no Parque Estadual do Turvo, Rio Grande do Sul, Brasil Composition and relative abundance of the medium-large ized mammals of Turvo State Park, Rio Grande do Sul, Brazil

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    Carlos B. Kasper

    2007-12-01

    Full Text Available Entre janeiro de 2005 e dezembro de 2006 foram realizados estudos sobre a composição e abundância relativa dos mamíferos de médio e grande porte do Parque Estadual do Turvo. Para tanto, foram utilizados registros de armadilhas fotográficas além de visualizações e dados sobre presença e ausência de pegadas ao longo de transectos pré-determinados. No total foram registradas 29 espécies de mamíferos de médio e grande porte, das quais Dasyprocta azarae Lichtenstein, 1823 e Sylvilagus brasiliensis (Linnaeus, 1758 foram as espécies com maior número de registros. No que se refere a Carnivora, Nasua nasua (Linnaeus, 1766 e Leopardus pardalis (Linnaeus, 1758 tiveram os maiores índices de registro, enquanto Leopardus tigrinus (Schreber, 1775, Leopardus wiedii (Schinz, 1782 e Galictis cuja (Molina 1782 os menores. Entre os ungulados apenas Pecari tajacu (Linnaeus, 1758 mostrou-se freqüente, sendo a quarta espécie em número de registros. Algumas espécies comuns em outros ambientes apresentaram baixos índices de registro no Parque Estadual do Turvo, tais como Dasypus novemcinctus Linnaeus, 1758 e Didelphis albiventris Lund, 1840. Finalmente, constata-se a provável extinção local de Tayassu pecari (Link, 1795, uma vez que não foram obtidos registros de sua presença ao longo do estudo. A conservação dos mamíferos de médio e grande porte do Parque está fortemente associada à preservação do "Corredor Verde de Misiones", que provavelmente representa uma área fonte para diversas espécies.Between January of 2005 and December of 2006, studies on the composition and relative abundance of medium and large sized mammals were carried out in Turvo State Park. Records came from camera-trapping, in addition to visualization and presence and absence data from track surveys along pre determined transects. At total, 29 species of medium-large sized mammals were listed. Of these, Dasyprocta azarae Lichtenstein, 1823 and Sylvilagus

  19. Observações sobre calazar em Jacobina, Bahia. VI - Investigações sobre reservatórios silvestres e comensais

    Directory of Open Access Journals (Sweden)

    I. A. Sherlock

    1988-03-01

    Full Text Available Durante os anos de 1982 a 1986, a investigação sobre mamíferos comensais e silvestres, da periferia da cidade de Jacobina, Bahia, mostrou, ao lado do escasso número de exemplares, uma reduzida variedade específica dessa fauna. Capturou-se apenas 11 espécies, entre as quais, predominou o Didelphis albiventris, que abrangeu 44% dos 213 espécimens capturados. Entre os 193 com exames já concluídos, 84 eram exemplares de D. albiventris e 2 estavam infectados pela Leishmania donovani senso lato, 1 por L. mexicana amazonensis, 1 por L. braziliensis, subespécie e 3 por Trypanosoma cruzi Também foram observadas formas suspeitas de serem amastigotas de leishmanics, nos esfregaços de órgãos de 3 exemplares de Dasyprocta aguti, 1 Cercomys cunicularius - e 1 Oryzomys eliurus. 0 restante dos exemplares, inclusive 14 de Lycalopex vetulus, estava negativo para flagelados. Apesar de reforçado por outros indicadores epidemiológicos, como a predominância específica, a freqüência domiciliar, a atratividade para a vetora Lutzomyia longipalpis, e a concomitância com casos humanos nos mesmos locais, o índice de 2,3% de infecção natural do Didelphis albiventris, não autoriza a conclusão definitiva de ser o marsupial o mais importante reservatório natural da leishmaniose visceral em Jacobina.From 1982 to 1986, investigations on the natural infection with leishmanias of the sylvatic and commensal mammals were carried out around the city of Jacobina, Bahia, one of the oldest endemic foci of visceral leishmaniasis in Brazil. The species of Marsupialia Didelphis albiventris predominated, with the rate of 44%, over the total of 213 specimens belonging to only 11 different species of mammals collected there. Among the 84 specimens of D. albiventris examined, 2(2.3% were infected with Leishmania donovani sensu lato; 1 with L. mexicana amazonensis, 1 with L. braziliensis sub species, and 3 with Trypanosoma cruzi. Also, amastigote suspected bodies were

  20. Environmentally associated ticks (Acari: Ixodidae in Campo Grande, Mato Grosso do Sul, Brazil Carrapatos (Acari: Ixodidae associados com o ambiente em Campo Grande, Mato Grosso do Sul, Brasil

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    Marcos Valério Garcia

    2013-03-01

    Full Text Available Herein, we report tick species found on wild and domestic animals and in the environment during a one-year sampling period at the Brazilian Farming Research Company beef cattle unit (Embrapa Beef Cattle, which is located within the urban area of Campo Grande, Mato Grosso do Sul, Brazil. From 55 wild hosts including six different species (Nasua nasua, Cebus spp., Cerdocyon thous, Myrmecophaga tridactyla, Tamandua tetradactyla and Dasyprocta aguti, 323 ticks were collected. Amblyomma ovale ticks were found solely on coatis, and Amblyomma nodosum was identified solely on anteaters. No ticks were found on capuchin monkeys. However, Amblyomma cajennense was found on all parasitized host species with the exception of capuchin monkeys. Giant anteaters displayed the highest infestation abundance, with a mean of 53 ticks∕animal. Environmental sampling yielded 166 adult A. cajennense ticks. The tick species found on domestic animals (Rhipicephalus (Boophilus microplus, R. sanguineus, Dermacentor nitens and A. cajennense were those typically found on these hosts in Brazil. The most prevalent tick species, A. cajennense, was found on both wild and domestic animals and was also prevalent in the environment. Thus, this tick species is the primary vector that allows pathogens to bridge wild and domestic animals in the Cerrado.Neste trabalho são descritas as espécies de carrapatos de animais selvagens e domésticos e do ambiente coletados por um ano na EMBRAPA Gado de Corte localizado na área urbana de Campo Grande, Mato Grosso do Sul, Brasil. Dos 55 hospedeiros selvagens de seis espécies diferentes (Nasua nasua, Cebus spp., Cerdocyon thous, Myrmecophaga tridactyla, Tamandua tetradactyla e Dasyprocta aguti foram coletados 323 carrapatos. Amblyomma ovale foi encontrado apenas em quatis e Amblyomma nodosum apenas sobre tamanduás. Nenhum carrapato foi encontrado sobre macacos-prego. Por outro lado, Amblyomma cajennense foi encontrado em todos os hospedeiros

  1. Composição e caracterização da fauna de mamíferos de médio e grande porte em uma pequena reserva de cerrado em Mato Grosso, Brasil Composition and characterization of the medium and large size mammal fauna in a small cerrado reserve in Mato Grosso, Brazil

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    Ednaldo Cândido Rocha

    2006-08-01

    Full Text Available Este estudo foi realizado na Reserva Biológica Municipal "Mário Viana", Nova Xavantina, MT, objetivando inventariar e avaliar a abundância e diversidade de mamíferos terrestres de médio e grande porte. Para tanto, foram realizadas duas visitas mensais a um transecto com 2.820 m de extensão, durante todo o ano de 2001, para o levantamento de pegadas (rastreamentos e outras evidências de mamíferos. Um total de 29 espécies foram registradas na área de estudo, sendo que 22 ocorreram no transecto e tiveram suas seqüências individuais de pegadas quantificadas para realização do cálculo dos índices de abundância e de diversidade de Shannon-Wiener (H'. De acordo com seus índices de abundância, as espécies foram classificadas em raras, comuns e abundantes. Dentre outras, onça-parda (Puma concolor - Linnaeus, 1771 e tatu-canastra (Priodontes maximus - Keer, 1792 mostraram-se raras; jaguatirica (Leopardus pardalis - Linnaeus, 1758, e tamanduá-bandeira (Myrmecophaga tridactyla - Linnaeus, 1758, comuns; e cutia (Dasyprocta azarae - Lichtenstein, 1823 e tapeti (Sylvilagus brasiliensis - Linnaeus, 1758, abundantes. O H' encontrado foi 2,40, sendo considerado significativo. O presente trabalho apontou que, apesar de pequena (470 ha, a área de estudo desempenha importante papel para a conservação da mastofauna da região de Nova Xavantina, MT.This study was carried out at the 'Mario Viana' Municipal Biological Reserve in Nova Xavantina, MT, aiming to make an inventory and evaluate the abundance and diversity of terrestrial mammals of medium and large size. Thus, two monthly visits were made to a 2.820 m long transect throughout 2001 to assess tracking and other evidences of mammals. Twenty-nine species were recorded in the study area, with 22 in the transect and two individual tracking sequences being quantified for calculation of the Shannon-Wiener (H' abundance and diversity indices. According to the abundance indices, the species were

  2. Observações sobre calazar em Jacobina, Bahia. VI - Investigações sobre reservatórios silvestres e comensais

    Directory of Open Access Journals (Sweden)

    I. A. Sherlock

    1988-03-01

    Full Text Available Durante os anos de 1982 a 1986, a investigação sobre mamíferos comensais e silvestres, da periferia da cidade de Jacobina, Bahia, mostrou, ao lado do escasso número de exemplares, uma reduzida variedade específica dessa fauna. Capturou-se apenas 11 espécies, entre as quais, predominou o Didelphis albiventris, que abrangeu 44% dos 213 espécimens capturados. Entre os 193 com exames já concluídos, 84 eram exemplares de D. albiventris e 2 estavam infectados pela Leishmania donovani senso lato, 1 por L. mexicana amazonensis, 1 por L. braziliensis, subespécie e 3 por Trypanosoma cruzi Também foram observadas formas suspeitas de serem amastigotas de leishmanics, nos esfregaços de órgãos de 3 exemplares de Dasyprocta aguti, 1 Cercomys cunicularius - e 1 Oryzomys eliurus. 0 restante dos exemplares, inclusive 14 de Lycalopex vetulus, estava negativo para flagelados. Apesar de reforçado por outros indicadores epidemiológicos, como a predominância específica, a freqüência domiciliar, a atratividade para a vetora Lutzomyia longipalpis, e a concomitância com casos humanos nos mesmos locais, o índice de 2,3% de infecção natural do Didelphis albiventris, não autoriza a conclusão definitiva de ser o marsupial o mais importante reservatório natural da leishmaniose visceral em Jacobina.

  3. Neuroendocrine and Molecular Interactions in Eating Disorders

    Directory of Open Access Journals (Sweden)

    Selma Bozkurt Zincir

    2014-08-01

    Full Text Available There are three basic pillars for the development of eating disorders: genetic predisposition, neuro-endocrine-molecular changes in the brain and metabolic response to it. As a result of neuroendocrine research, a close relationship has been found between neuroendocrine functions and symptom domains of psychiatric disorders such as eating disorders and mood disorders. Certain hormones, neurotransmitters and other molecules which might have effect on the basis of eating disorders can be listed as estrogen, serotonin, leptin, ghreline, alpha-melanocyte stimulating hormone, cholecystokinin, dopamine, noradrenaline, brain-derived neurotropic factor, agouti-related protein, neuropeptide-Y, opioids and their receptors, thiamine, zinc, omega-3 acids. In this review, main neuroendocrine-molecular changes and interactions that occur in the eating disorders have been discussed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 389-400

  4. Mammalian comparative sequence analysis of the Agrp locus.

    Directory of Open Access Journals (Sweden)

    Christopher B Kaelin

    Full Text Available Agouti-related protein encodes a neuropeptide that stimulates food intake. Agrp expression in the brain is restricted to neurons in the arcuate nucleus of the hypothalamus and is elevated by states of negative energy balance. The molecular mechanisms underlying Agrp regulation, however, remain poorly defined. Using a combination of transgenic and comparative sequence analysis, we have previously identified a 760 bp conserved region upstream of Agrp which contains STAT binding elements that participate in Agrp transcriptional regulation. In this study, we attempt to improve the specificity for detecting conserved elements in this region by comparing genomic sequences from 10 mammalian species. Our analysis reveals a symmetrical organization of conserved sequences upstream of Agrp, which cluster into two inverted repeat elements. Conserved sequences within these elements suggest a role for homeodomain proteins in the regulation of Agrp and provide additional targets for functional evaluation.

  5. Inheritance of goat coat colors.

    Science.gov (United States)

    Adalsteinsson, S; Sponenberg, D P; Alexieva, S; Russel, A J

    1994-01-01

    Goat color inheritance was evaluated based on color description of 218 kids and their parents (10 sires, 178 dams) from mixed crosses between several goat populations in an experiment on cashmere fiber production. Altogether 10 color patterns were observed. They were postulated to be caused by 10 alleles at the Agouti locus, with the allele for white or tan color being the top dominant allele, and the nine others codominant. The bottom recessive allele, for nonagouti color, was the 11th allele at this locus. The postulated alleles are white or tan (A(wt)), black mask (A(blm)), bezoar (A(bz)), badgerface (A(b)), grey (A(g)), lightbelly (A(lb)), swiss markings (A(sm)), lateral stripes (A(ls)), mahogany (A(mh)), red cheek (A(rc)), and nonagouti (Aa). Two types of eumelanin pigment were observed, black and light brown, the latter being dominant. Recessive brown was not observed.

  6. Peromyscus as a Mammalian Epigenetic Model

    Directory of Open Access Journals (Sweden)

    Kimberly R. Shorter

    2012-01-01

    Full Text Available Deer mice (Peromyscus offer an opportunity for studying the effects of natural genetic/epigenetic variation with several advantages over other mammalian models. These advantages include the ability to study natural genetic variation and behaviors not present in other models. Moreover, their life histories in diverse habitats are well studied. Peromyscus resources include genome sequencing in progress, a nascent genetic map, and >90,000 ESTs. Here we review epigenetic studies and relevant areas of research involving Peromyscus models. These include differences in epigenetic control between species and substance effects on behavior. We also present new data on the epigenetic effects of diet on coat-color using a Peromyscus model of agouti overexpression. We suggest that in terms of tying natural genetic variants with environmental effects in producing specific epigenetic effects, Peromyscus models have a great potential.

  7. Tyrosinase Depletion Prevents the Maturation of Melanosomes in the Mouse Hair Follicle.

    Directory of Open Access Journals (Sweden)

    Elyse K Paterson

    Full Text Available The mechanisms that lead to variation in human skin and hair color are not fully understood. To better understand the molecular control of skin and hair color variation, we modulated the expression of Tyrosinase (Tyr, which controls the rate-limiting step of melanogenesis, by expressing a single-copy, tetracycline-inducible shRNA against Tyr in mice. Moderate depletion of TYR was sufficient to alter the appearance of the mouse coat in black, agouti, and yellow coat color backgrounds, even though TYR depletion did not significantly inhibit accumulation of melanin within the mouse hair. Ultra-structural studies revealed that the reduction of Tyr inhibited the accumulation of terminal melanosomes, and inhibited the expression of genes that regulate melanogenesis. These results indicate that color in skin and hair is determined not only by the total amount of melanin within the hair, but also by the relative accumulation of mature melanosomes.

  8. Tyrosinase Depletion Prevents the Maturation of Melanosomes in the Mouse Hair Follicle.

    Science.gov (United States)

    Paterson, Elyse K; Fielder, Thomas J; MacGregor, Grant R; Ito, Shosuke; Wakamatsu, Kazumasa; Gillen, Daniel L; Eby, Victoria; Boissy, Raymond E; Ganesan, Anand K

    2015-01-01

    The mechanisms that lead to variation in human skin and hair color are not fully understood. To better understand the molecular control of skin and hair color variation, we modulated the expression of Tyrosinase (Tyr), which controls the rate-limiting step of melanogenesis, by expressing a single-copy, tetracycline-inducible shRNA against Tyr in mice. Moderate depletion of TYR was sufficient to alter the appearance of the mouse coat in black, agouti, and yellow coat color backgrounds, even though TYR depletion did not significantly inhibit accumulation of melanin within the mouse hair. Ultra-structural studies revealed that the reduction of Tyr inhibited the accumulation of terminal melanosomes, and inhibited the expression of genes that regulate melanogenesis. These results indicate that color in skin and hair is determined not only by the total amount of melanin within the hair, but also by the relative accumulation of mature melanosomes. PMID:26619124

  9. Determinants of body weight regulation in humans.

    Science.gov (United States)

    Moehlecke, Milene; Canani, Luis Henrique; Silva, Lucas Oliveira Junqueira E; Trindade, Manoel Roberto Maciel; Friedman, Rogerio; Leitão, Cristiane Bauermann

    2016-04-01

    Body weight is regulated by the ability of hypothalamic neurons to orchestrate behavioral, endocrine and autonomic responses via afferent and efferent pathways to the brainstem and the periphery. Weight maintenance requires a balance between energy intake and energy expenditure. Although several components that participate in energy homeostasis have been identified, there is a need to know in more detail their actions as well as their interactions with environmental and psychosocial factors in the development of human obesity. In this review, we examine the role of systemic mediators such as leptin, ghrelin and insulin, which act in the central nervous system by activating or inhibiting neuropeptide Y, Agouti-related peptide protein, melanocortin, transcript related to cocaine and amphetamine, and others. As a result, modifications in energy homeostasis occur through regulation of appetite and energy expenditure. We also examine compensatory changes in the circulating levels of several peripheral hormones after diet-induced weight loss. PMID:26910628

  10. Cannabinoid treatment renders neurons less vulnerable than oligodendrocytes in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Hasseldam, Henrik; Johansen, Flemming Fryd

    2011-01-01

    effects. EAE was induced using MOG(1-125) in Dark Agouti rats and treatment was initiated at symptom debut and continued until first relapse culminated. The central nervous system (CNS) cell death including caspase and calpain activation, axonal degeneration and demyelination as well as a wide range......ABSTRACT Using the rat model Experimental Autoimmune Encephalomyelitis (EAE), we have investigated the cytokinetical and cellular events of axonal degeneration and demyelination following treatment with 5 mg/kg/24h R(+)WIN55,212-2 or 10 mg/kg/24h R(+)WIN55,212-2, which have immunosuppressive...... of immunological parameters were quantified. We found a significant reduction in axonal degeneration associated with reduced calpain 1 following treatment with 5 mg/kg/24h R(+)WIN55,212-2. Treatment with 10 mg/kg/24h resulted furthermore in an improved clinical performance and a reduction in inflammatory activity...

  11. Effects of "Bioactive" amino acids leucine, glutamate, arginine and tryptophan on feed intake and mRNA expression of relative neuropeptides in broiler chicks

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    Wang Songbo

    2012-08-01

    Full Text Available Abstract Feed intake control is vital to ensuring optimal nutrition and achieving full potential for growth and development in poultry. The aim of the present study was to investigate the effects of L-leucine, L-glutamate, L-tryptophan and L-arginine on feed intake and the mRNA expression levels of hypothalamic Neuropeptide involved in feed intake regulation in broiler chicks. Leucine, glutamate, tryptophan or arginine was intra-cerebroventricularly (ICV administrated to 4d-old broiler chicks respectively and the feed intake were recorded at various time points. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of Neuropeptide Y (NPY, agouti related protein (AgRP, pro-opiomelanocortin (POMC, melanocortin receptor 4 (MC4R and corticotrophin releasing factor (CRF. Our results showed that ICV administration of L-leucine (0.15 or 1.5  μmol significantly (P P 

  12. Food intake regulating-neuropeptides are expressed and regulated through pregnancy and following food restriction in rat placenta

    Directory of Open Access Journals (Sweden)

    Cepeda Libia A

    2008-04-01

    Full Text Available Abstract Background Neuropeptide Y (NPY, agouti related peptide (AgRP, cocaine and amphetamine-regulated transcript (CART and melanocortins, the products of the proopiomelanocortin (POMC, are hypothalamic peptides involved in feeding regulation and energy homeostasis. Recent evidence has demonstrated their expression in rat and human placenta. Methods In the current study, we have investigated the expression of those neuropeptides in the rat placenta by real-time PCR using a model of maternal food restriction. Results Our results showed that placental-derived neuropeptides were regulated through pregnancy and following food restriction. Conclusion These data could indicate that placental-derived neuropeptides represent a local regulatory circuit that may fine-tune control of energy balance during pregnancy.

  13. Impact of animal strain on gene expression in a rat model of acute cardiac rejection

    Directory of Open Access Journals (Sweden)

    Norsworthy Kelly J

    2009-06-01

    Full Text Available Abstract Background The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR. Using a rat heart transplant model and 2 different rat strains (Dark Agouti, and Brown Norway, microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC. Results In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ≥ 3. Only 13 genes were affected by both strain and rejection, which was Conclusion In ACR, genetic background has a large impact on the transcriptome of immune cells, but not heart tissue. Gene expression studies of ACR should avoid study designs that require cross strain comparisons between leukocytes.

  14. mTORC1 signaling in Agrp neurons mediates circadian expression of Agrp and NPY but is dispensable for regulation of feeding behavior.

    Science.gov (United States)

    Albert, Verena; Cornu, Marion; Hall, Michael N

    2015-08-21

    Orexigenic agouti-related protein/neuropeptide Y (Agrp/NPY) neurons and an orexigenic pro-opiomelanocortin (POMC) neurons of the hypothalamus regulate feeding behavior and energy homeostasis. An understanding of the molecular signaling pathways that regulate Agrp/NPY and POMC function could lead to novel treatments for metabolic disorders. Target of Rapamycin Complex 1 (TORC1) is a nutrient-activated protein kinase and central controller of growth and metabolism. We therefore investigated the role of mammalian TORC1 (mTORC1) in Agrp neurons. We generated and characterized Agrp neuron-specific raptor knockout (Agrp-raptor KO) mice. Agrp-raptor KO mice displayed reduced, non-circadian expression of Agrp and NPY but normal feeding behavior and energy homeostasis on both normal and high fat diet. Thus, mTORC1 in Agrp neurons controls circadian expression of orexigenic neuropeptides but is dispensable for the regulation of feeding behavior and energy metabolism.

  15. Lack of genetic association among coat colors, progressive retinal atrophy and polycystic kidney disease in Persian cats.

    Science.gov (United States)

    Rah, HyungChul; Maggs, David J; Lyons, Leslie A

    2006-10-01

    An inherited form of progressive retinal atrophy (PRA) is recognized in Persian cats; however, the prevalence of PRA in the breed has not been determined. Breeders suggest that cats from only brown ('chocolate') or Himalayan ('pointed') lines are at risk for PRA, suggesting the disease is not widespread. This study was designed to evaluate whether PRA in Persian cats is associated with three coat colors, including chocolate, or with a highly prevalent inherited disease in this breed--polycystic kidney disease (PKD). Sixty related cats were evaluated for PRA by ophthalmic examination and genetically typed for PKD and the mutations that cause coat color variants in agouti, brown and color (producing the pointed coloration in Himalayan). No associations were identified among any of the traits, including between PRA and chocolate. These data suggest that PRA is not limited to cats with chocolate coat coloration and breeders and veterinarians should be aware that the prevalence of the disease may be higher than currently claimed.

  16. Epigenomic Adaptation to Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gould, Michael N. [Univ. of Wisconsin, Madison, WI (United States)

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  17. Adaptive evolution of multiple traits through multiple mutations at a single gene.

    Science.gov (United States)

    Linnen, Catherine R; Poh, Yu-Ping; Peterson, Brant K; Barrett, Rowan D H; Larson, Joanna G; Jensen, Jeffrey D; Hoekstra, Hopi E

    2013-03-15

    The identification of precise mutations is required for a complete understanding of the underlying molecular and evolutionary mechanisms driving adaptive phenotypic change. Using plasticine models in the field, we show that the light coat color of deer mice that recently colonized the light-colored soil of the Nebraska Sand Hills provides a strong selective advantage against visually hunting predators. Color variation in an admixed population suggests that this light Sand Hills phenotype is composed of multiple traits. We identified distinct regions within the Agouti locus associated with each color trait and found that only haplotypes associated with light trait values have evidence of selection. Thus, local adaptation is the result of independent selection on many mutations within a single locus, each with a specific effect on an adaptive phenotype, thereby minimizing pleiotropic consequences. PMID:23493712

  18. 绵羊黑色素合成相关基因的研究进展%Research Progress of Genes Related to Melanin Synthesis in Sheep

    Institute of Scientific and Technical Information of China (English)

    孟浩浩; 许瑞霞; 代蓉; 李辉; 李良远; 万鹏程; 石国庆

    2014-01-01

    毛色是一种可利用的遗传标记。在确定杂交组合、品种纯度和亲缘关系以及评价产品质量等方面均有一定的用途。哺乳动物毛色是由黑色素细胞产生的真黑素和褐黑素二者的分布和比例决定的。控制哺乳动物毛色色素的基因有很多,着重对黑色素合成相关基因酪氨酸酶基因(TYR)、黑素皮质激素受体1基因(MC1R)、鼠灰信号蛋白基因(Agouti)、酪氨酸酶相关蛋白1基因(TYRP1)的生物学功能及其遗传变异机制进行了综述。%As a genetic marker,coat color plays an important roles in determining cross combination,breed purity and phylogenesis. Coat color of mammals is determined by the distribution and proportion of eumelanin and pheomelanin,which produced by melanocytes. This article summarized the biological functions and the genetic variation of Tyrosinase gene(Tyr),Melanocortin 1 receptor gene(MC1R),Agouti signaling protein gene(Agouti)and Tyrosinase-related protein gene(TYRP1).

  19. Plumage Genes and Little Else Distinguish the Genomes of Hybridizing Warblers.

    Science.gov (United States)

    Toews, David P L; Taylor, Scott A; Vallender, Rachel; Brelsford, Alan; Butcher, Bronwyn G; Messer, Philipp W; Lovette, Irby J

    2016-09-12

    When related taxa hybridize extensively, their genomes may become increasingly homogenized over time. This mixing via hybridization creates conservation challenges when it reduces genetic or phenotypic diversity and when it endangers previously distinct species via genetic swamping [1]. However, hybridization also facilitates admixture mapping of traits that distinguish each species and the associated genes that maintain distinctiveness despite ongoing gene flow [2]. We address these dual aspects of hybridization in the golden-winged/blue-winged warbler complex, two phenotypically divergent warblers that are indistinguishable using traditional molecular markers and that draw substantial conservation attention [3-5]. Whole-genome comparisons show that differentiation is extremely low: only six small genomic regions exhibit strong differences. Four of these divergence peaks occur in proximity to genes known to be involved in feather development or pigmentation: agouti signaling protein (ASIP), follistatin (FST), ecodysplasin (EDA), wingless-related integration site (Wnt), and beta-carotene oxygenase 2 (BCO2). Throat coloration-the most striking plumage difference between these warblers-is perfectly associated with the promoter region of agouti, and genotypes at this locus obey simple Mendelian recessive inheritance of the black-throated phenotype characteristic of golden-winged warblers. The more general pattern of genomic similarity between these warblers likely results from a protracted period of hybridization, contradicting the broadly accepted hypothesis that admixture results from solely anthropogenic habitat change in the past two centuries [4]. Considered in concert, these results are relevant to both the genetic architecture of avian feather pigmentation and the evolutionary history and conservation challenges associated with these declining songbirds. PMID:27546575

  20. Hypothalamic neuropeptide gene expression during recovery from food restriction superimposed on short-day photoperiod-induced weight loss in the Siberian hamster.

    Science.gov (United States)

    Archer, Zoë A; Moar, Kim M; Logie, Tracy J; Reilly, Laura; Stevens, Valerie; Morgan, Peter J; Mercer, Julian G

    2007-09-01

    Previously, 40% food restriction of male Siberian hamsters over 21 days in short-day (SD) photoperiod induced characteristic changes in expression of hypothalamic arcuate nucleus energy balance genes; mRNAs for neuropeptide Y, agouti-related peptide, and leptin receptor were upregulated, and those of proopiomelanocortin and cocaine- and amphetamine-regulated transcript were depressed. The present study examined the effect of refeeding hamsters for 6 days (approximately 50% recovery of weight differential) or 19 days (resumption of appropriate weight trajectory). Hyperphagia continued throughout refeeding, but differences in fat pad weights and leptin levels had disappeared after 19 days. Cocaine- and amphetamine-regulated transcript gene expression was depressed by prior restriction in both refed groups. The depressive effect of prior restriction on proopiomelanocortin gene expression had disappeared after 19 days of refeeding. There was no effect of prior food restriction on neuropeptide Y or agouti-related peptide gene expression. Expression of the anorexigenic brain-derived neurotrophic factor was downregulated in the ventromedial nucleus after SD exposure for 12 wk. In the SD food restriction study, there were effects of photoperiod on brain-derived neurotrophic factor gene expression but not of prior food restriction. Hypothalamic energy balance genes in the hamster respond asynchronously to return to a seasonally appropriate body weight. The achievement of this weight rather than the weight at which caloric restriction was imposed is the critical factor. The differential responses of hypothalamic energy balance genes to food restriction and refeeding are poorly characterized in any species, a critical issue given their potential relevance to human weight loss strategies that involve caloric restriction.

  1. Hypothalamic Non-AgRP, Non-POMC GABAergic Neurons Are Required for Postweaning Feeding and NPY Hyperphagia.

    Science.gov (United States)

    Kim, Eun Ran; Wu, Zhaofei; Sun, Hao; Xu, Yuanzhong; Mangieri, Leandra R; Xu, Yong; Tong, Qingchun

    2015-07-22

    The hypothalamus is critical for feeding and body weight regulation. Prevailing studies focus on hypothalamic neurons that are defined by selectively expressing transcription factors or neuropeptides including those expressing proopiomelanocortin (POMC) and agouti-related peptides (AgRP). The Cre expression driven by the pancreas-duodenum homeobox 1 promoter is abundant in several hypothalamic nuclei but not in AgRP or POMC neurons. Using this line, we generated mice with disruption of GABA release from a major subset of non-POMC, non-AgRP GABAergic neurons in the hypothalamus. These mice exhibited a reduction in postweaning feeding and growth, and disrupted hyperphagic responses to NPY. Disruption of GABA release severely diminished GABAergic input to the paraventricular hypothalamic nucleus (PVH). Furthermore, disruption of GABA-A receptor function in the PVH also reduced postweaning feeding and blunted NPY-induced hyperphagia. Given the limited knowledge on postweaning feeding, our results are significant in identifying GABA release from a major subset of less appreciated hypothalamic neurons as a key mediator for postweaning feeding and NPY hyperphagia, and the PVH as one major downstream site that contributes significantly to the GABA action. Significance statement: Prevalent studies on feeding in the hypothalamus focus on well characterized, selective groups neurons [e.g., proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons], and as a result, the role of the majority of other hypothalamic neurons is largely neglected. Here, we demonstrated an important role for GABAergic projections from non-POMC non-AgRP neurons to the paraventricular hypothalamic nucleus in promoting postweaning (mainly nocturnal) feeding and mediating NPY-induced hyperphagia. Thus, these results signify an importance to study those yet to be defined hypothalamic neurons in the regulation of energy balance and reveal a neural basis for postweaning (nocturnal) feeding and

  2. @@%Agouti与MITF在不同颜色被毛藏羊皮肤组织中mRNA表达量研究

    Institute of Scientific and Technical Information of China (English)

    韩吉龙; 杨博辉; 岳耀敬; 郭健; 刘建斌; 牛春娥; 郭婷婷; 冯瑞林; 孙晓萍; 吴瑜瑜

    2012-01-01

    @@%为了研究决定藏羊不同颜色被毛形成的分子机制,采用实时荧光定量PCR检测皮肤组织中决定色素形成信号通路中上游调控刺鼠信号蛋白基因(agouti signaling protein (ASIP) gene,Agouti)和下游调控小眼畸形相关转录因子基因(microphthalmia-associated transcription factor,MITF)mRNA的相对表达量,分析同一基因在黑色眼圈、棕黑色颈部和白色体侧被毛皮肤组织的相对表达量差异,对两基因在同一个体同一颜色被毛皮肤组织表达量进行相关性分析.结果表明:Agouti基因在同一个体mRNA表达水平为棕黑色皮肤组织显著性高于黑色和白色(P<0.05),MITF基因mRNA表达量黑色皮肤组织显著性高于棕黑色和白色(P<0.05).通过相关性分析得知,两基因在同一个体同一毛色皮肤组织mRNA相对表达量无显著相关性.推论得知,MITF基因mRNA高表达与藏羊眼圈周围黑色被毛显著相关,Agouti基因mRNA高表达、MITF基因mRNA低表达与其颈部棕黑色被毛可能为其原因,体侧部的白色毛与Agouti和MITF基因mRNA表达无明显相关.

  3. Heparanase affects food intake and regulates energy balance in mice.

    Directory of Open Access Journals (Sweden)

    Linda Karlsson-Lindahl

    Full Text Available Mutation of the melanocortin-receptor 4 (MC4R is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.

  4. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Tadashi Okamura

    2013-01-01

    Full Text Available Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA rat derived from Long-Evans (LE strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

  5. Changes in Ghrelin-Related Factors in Gastroesophageal Reflux Disease in Rats

    Directory of Open Access Journals (Sweden)

    Miwa Nahata

    2013-01-01

    Full Text Available To examine gastrointestinal hormone profiles and functional changes in gastroesophageal reflux disease (GERD, blood levels of the orexigenic hormone ghrelin were measured in rats with experimentally induced GERD. During the experiment, plasma acyl ghrelin levels in GERD rats were higher than those in sham-operated rats, although food intake was reduced in GERD rats. Although plasma levels of the appetite-suppressing hormone leptin were significantly decreased in GERD rats, no changes were observed in cholecystokinin levels. Repeated administration of rat ghrelin to GERD rats had no effect on the reduction in body weight or food intake. Therefore, these results suggest that aberrantly increased secretion of peripheral ghrelin and decreased ghrelin responsiveness may occur in GERD rats. Neuropeptide Y and agouti-related peptide mRNA expression in the hypothalamus of GERD rats was significantly increased, whereas proopiomelanocortin mRNA expression was significantly decreased compared to that in sham-operated rats. However, melanin-concentrating hormone (MCH and prepro-orexin mRNA expression in the hypothalamus of GERD rats was similar to that in sham-operated rats. These results suggest that although GERD rats have higher plasma ghrelin levels, ghrelin signaling in GERD rats may be suppressed due to reduced MCH and/or orexin synthesis in the hypothalamus.

  6. Mouse estrous cycle identification tool and images.

    Directory of Open Access Journals (Sweden)

    Shannon L Byers

    Full Text Available The efficiency of producing timed pregnant or pseudopregnant mice can be increased by identifying those in proestrus or estrus. Visual observation of the vagina is the quickest method, requires no special equipment, and is best used when only proestrus or estrus stages need to be identified. Strain to strain differences, especially in coat color can make it difficult to determine the stage of the estrous cycle accurately by visual observation. Presented here are a series of images of the vaginal opening at each stage of the estrous cycle for 3 mouse strains of different coat colors: black (C57BL/6J, agouti (CByB6F1/J and albino (BALB/cByJ. When all 4 stages (proestrus, estrus, metestrus, and diestrus need to be identified, vaginal cytology is regarded as the most accurate method. An identification tool is presented to aid the user in determining the stage of estrous when using vaginal cytology. These images and descriptions are an excellent resource for learning how to determine the stage of the estrous cycle by visual observation or vaginal cytology.

  7. Orally available selective melanocortin-4 receptor antagonists stimulate food intake and reduce cancer-induced cachexia in mice.

    Directory of Open Access Journals (Sweden)

    Philipp Weyermann

    Full Text Available BACKGROUND: Cachexia is among the most debilitating and life-threatening aspects of cancer. It represents a metabolic syndrome affecting essential functional circuits involved in the regulation of homeostasis, and includes anorexia, fat and muscle tissue wasting. The anorexigenic peptide alpha-MSH is believed to be crucially involved in the normal and pathologic regulation of food intake. It was speculated that blockade of its central physiological target, the melanocortin (MC-4 receptor, might provide a promising anti-cachexia treatment strategy. This idea is supported by the fact that in animal studies, agouti-related protein (AgRP, the endogenous inverse agonist at the MC-4 receptor, was found to affect two hallmark features of cachexia, i.e. to increase food intake and to reduce energy expenditure. METHODOLOGY/PRINCIPAL FINDINGS: SNT207707 and SNT209858 are two recently discovered, non peptidic, chemically unrelated, orally active MC-4 receptor antagonists penetrating the blood brain barrier. Both compounds were found to distinctly increase food intake in healthy mice. Moreover, in mice subcutaneously implanted with C26 adenocarcinoma cells, repeated oral administration (starting the day after tumor implantation of each of the two compounds almost completely prevented tumor induced weight loss, and diminished loss of lean body mass and fat mass. CONCLUSIONS/SIGNIFICANCE: In contrast to the previously reported peptidic and small molecule MC-4 antagonists, the compounds described here work by the oral administration route. Orally active compounds might offer a considerable advantage for the treatment of cachexia patients.

  8. Temporal Change in Fur Color in Museum Specimens of Mammals: Reddish-Brown Species Get Redder with Storage Time

    Directory of Open Access Journals (Sweden)

    Andrew K. Davis

    2013-01-01

    Full Text Available Museum collections have great value for zoological research, but despite careful preservation, over time specimens can show subtle changes in color. We examined the effect of storage time on fur color of two reddish-brown species, golden mice (Ochrotomys nuttalli and eastern chipmunk (Tamias striatus. Using image analysis, we obtained color data (hue, saturation, and density on 91 golden mice and 49 chipmunks from Georgia, USA. Analyses that considered body size, gender, and collection year showed significant effects of year on fur color of golden mice (hue and saturation and of agouti color of chipmunks. Older specimens tended to be redder in color than newer specimens, consistent with a prior study of red bats (Lasiurus borealis. Hair samples showed reddening of fine body hairs, but not in thicker guard hairs. There was no temporal change in black or white stripe color in chipmunks, indicating that this temporal effect would be limited to species with reddish-brown fur. This effect may be caused by breakdown of eumelanin pigments (which make dark colors over time, leaving a greater proportion of pheomelanin pigments (which make red colors. These results show that storage time needs to be considered in research projects where fur color is of importance.

  9. Neuroregulation of nonexercise activity thermogenesis and obesity resistance.

    Science.gov (United States)

    Kotz, Catherine M; Teske, Jennifer A; Billington, Charles J

    2008-03-01

    High levels of spontaneous physical activity in lean people and the nonexercise activity thermogenesis (NEAT) derived from that activity appear to protect lean people from obesity during caloric challenge, while obesity in humans is characterized by dramatically reduced spontaneous physical activity. We have similarly demonstrated that obesity-resistant rats have significantly greater spontaneous physical activity than obesity-prone rats, and that spontaneous physical activity predicts body weight gain. Although the energetic cost of activity varies between types of activity and may be regulated, individual level of spontaneous physical activity is important in determining propensity for obesity. We review the current status of knowledge about the brain mechanisms involved in controlling the level of spontaneous physical activity and the NEAT so generated. Focus is on potential neural mediators of spontaneous physical activity and NEAT, including orexin A (also known as hypocretin 1), agouti-related protein, ghrelin, and neuromedin U, in addition to brief mention of neuropeptide Y, corticotrophin releasing hormone, cholecystokinin, estrogen, leptin, and dopamine effects on spontaneous physical activity. We further review evidence that strain differences in orexin stimulation pathways for spontaneous physical activity and NEAT appear to track with the body weight phenotype, thus providing a potential mechanistic explanation for reduced activity and weight gain. PMID:18160530

  10. A high-throughput fluorescence-based assay system for appetite-regulating gene and drug screening.

    Directory of Open Access Journals (Sweden)

    Yasuhito Shimada

    Full Text Available The increasing number of people suffering from metabolic syndrome and obesity is becoming a serious problem not only in developed countries, but also in developing countries. However, there are few agents currently approved for the treatment of obesity. Those that are available are mainly appetite suppressants and gastrointestinal fat blockers. We have developed a simple and rapid method for the measurement of the feeding volume of Danio rerio (zebrafish. This assay can be used to screen appetite suppressants and enhancers. In this study, zebrafish were fed viable paramecia that were fluorescently-labeled, and feeding volume was measured using a 96-well microplate reader. Gene expression analysis of brain-derived neurotrophic factor (bdnf, knockdown of appetite-regulating genes (neuropeptide Y, preproinsulin, melanocortin 4 receptor, agouti related protein, and cannabinoid receptor 1, and the administration of clinical appetite suppressants (fluoxetine, sibutramine, mazindol, phentermine, and rimonabant revealed the similarity among mechanisms regulating appetite in zebrafish and mammals. In combination with behavioral analysis, we were able to evaluate adverse effects on locomotor activities from gene knockdown and chemical treatments. In conclusion, we have developed an assay that uses zebrafish, which can be applied to high-throughput screening and target gene discovery for appetite suppressants and enhancers.

  11. Pulmonary Immune Responses to Aspergillus Fumigatus in Rats

    Institute of Scientific and Technical Information of China (English)

    MIRKOV Ivana; EL-MUZGHI Amal Atia Mhfuod; DJOKIC Jelena; NINKOV Marina; POPOV ALEKSANDROV Aleksandra; GLAMOCLIJA Jasmina; KATARANOVSKI Milena

    2014-01-01

    Objective To evaluate immunologic mechanisms underlying Aspergillus fumigatus pulmonary infections in immunocompetent Dark Agouti (DA) and Albino Oxford (AO) rats recognized as being susceptible to some inflammatory diseases in different manners. Methods Lung fungal burden (quantitative colony forming units, CFU, assay), leukocyte infiltration (histology, cell composition) and their function (phagocytosis, oxidative activity, CD11b adhesion molecule expression) and cytokine interferon-γ(IFN-γ) and interleukin-17 and-4 (IL-17 and IL-4) lung content were evaluated following infection (intratracheally, 1x107 conidia). Results Slower reduction of fungal burden was observed in AO rats in comparison with that in DA rats, which was coincided with less intense histologically evident lung cell infiltration and leukocyte recovery as well as lower level of most of the their activities including intracellular myeloperoxidase activity, the capacity of nitroblue tetrazolium salt reduction and CD11b adhesion molecule expression (except for phagocytosis of conidia) in these rats. Differential patterns of changes in proinflammatory cytokine levels (unchanged levels of IFN-γand transient increase of IL-17 in AO rats vs continuous increase of both cytokines in DA rats) and unchanged levels of IL-4 were observed. Conclusion Genetically-based differences in the pattern of antifungal lung leukocyte activities and cytokine milieu, associated with differential efficiency of fungal elimination might be useful in the future use of rat models in studies of pulmonary aspergillosis.

  12. Use of FK506 and bone marrow mesenchymal stem cells for rat hind limb allografts

    Institute of Scientific and Technical Information of China (English)

    Youxin Song; Zhujun Wang; Zhixue Wang; Hong Zhang; Xiaohui Li; Bin Chen

    2012-01-01

    Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance. bone marrow mesenchymal stem cells were intramuscularly (gluteus maximus) injected with FK506 (tacrolimus) daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 + bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 + bone marrow mesenchymal stem cells group. The FK506 + bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.

  13. Strain difference in T-cell regulation of antibody response to polyvinylpyrrolidone. [Mice, x radiation

    Energy Technology Data Exchange (ETDEWEB)

    Muraoka, S.; Nomoto, K.; Imada, Y.; Takeya, K.

    1977-09-01

    Antibody response to polyvinylpyrrolidone (PVP), one of the thymus-independent antigens, was assessed by a passive hemagglutination test and a plaque-forming cell assay in three inbred mouse strains. C3H/He, AKR, and C57BL/6 mice were assigned to groups of high, intermediate, and low responders, respectively. This strain difference appears to be ascribable to the differences in the regulatory functions of T cells and in the responsiveness of B cells, as suggested by the antibody responses in mice partially or almost completely depleted of T cells. Genetic analysis of F/sub 1/ hybrids and their backcrosses suggested that at least two genes control the antibody response to PVP: One gene may regulate the responsiveness of B cells and another may govern the functions of T cells as a suppressor or an amplifier. The association between high responsiveness to PVP and an agouti coat color was suggested by a statistical analysis of the results in the backcrosses, but an association between the responsiveness and the sex of the mice was not found.

  14. Interleukin-7, a new cytokine targeting the mouse hypothalamic arcuate nucleus: role in body weight and food intake regulation.

    Directory of Open Access Journals (Sweden)

    Laurence Macia

    Full Text Available Body weight is controlled through peripheral (white adipose tissue and central (mainly hypothalamus mechanisms. We have recently obtained evidence that overexpression of interleukin (IL-7, a critical cytokine involved in lymphopoiesis, can protect against the development of diet-induced obesity in mice. Here we assessed whether IL-7 mediated its effects by modulating hypothalamic function. Acute subcutaneous injection of IL-7 prevented monosodium glutamate-induced obesity, this being correlated with partial protection against cell death in the hypothalamic arcuate nucleus (ARC. Moreover, we showed that IL-7 activated hypothalamic areas involved in regulation of feeding behavior, as indicated by induction of the activation marker c-Fos in neural cells located in the ventromedial part of the ARC and by inhibition of food intake after fasting. Both chains of the IL-7 receptor (IL-7Ralpha and gamma(c were expressed in the ARC and IL-7 injection induced STAT-3 phosphorylation in this area. Finally, we established that IL-7 modulated the expression of neuropeptides that tune food intake, with a stimulatory effect on the expression of pro-opiomelanocortin and an inhibitory effect on agouti-related peptide expression in accordance with IL-7 promoting anorectic effects. These results suggest that the immunomodulatory cytokine IL-7 plays an important and unappreciated role in hypothalamic body weight regulation.

  15. Antigen dose and strain variation as factors in the genetic control of the immune response to sperm whale myoglobin

    International Nuclear Information System (INIS)

    The primary and secondary immune response to the antigen sperm whale myoglobin was investigated in DBA/2, 129 and B10.BR mice over a dose range of immunization from 10 to 2000 μg. Using an antigen excess technique, the quantity of antibody produced after secondary immunization followed a sigmoidal dose-response curve and the maximal plateau level was found to be different for each strain of mice. Furthermore, the genetic control of the immune response was investigated in twelve different inbred strains of mice following secondary immunization with 500 μg of of myoglobin. A continuous distribution for the mean antibody responses was obtained for the twelve different strains of mice. High responsiveness was associated with H-2 haplotypes d, f and k located on chromosome 17, the non-agouti gene 'a' located on chromosome 2 and the chinchilla gene 'csup(ch)' located on chromosome 7. It is concluded that either a large number of IR-genes to myoglobin are present in many loci located on different chromosomes or the antibody differences could be explained by a cross-tolerance mechanism requiring no IR-genes at all. (author)

  16. Donor Heart Treatment With COMP-Ang1 Limits Ischemia-Reperfusion Injury and Rejection of Cardiac Allografts.

    Science.gov (United States)

    Syrjälä, S O; Nykänen, A I; Tuuminen, R; Raissadati, A; Keränen, M A I; Arnaudova, R; Krebs, R; Koh, G Y; Alitalo, K; Lemström, K B

    2015-08-01

    The major cause of death during the first year after heart transplantation is primary graft dysfunction due to preservation and ischemia-reperfusion injury (IRI). Angiopoietin-1 is a Tie2 receptor-binding paracrine growth factor with anti-inflammatory properties and indispensable roles in vascular development and stability. We used a stable variant of angiopoietin-1 (COMP-Ang1) to test whether ex vivo intracoronary treatment with a single dose of COMP-Ang1 in donor Dark Agouti rat heart subjected to 4-h cold ischemia would prevent microvascular dysfunction and inflammatory responses in the fully allogeneic recipient Wistar Furth rat. COMP-Ang1 reduced endothelial cell-cell junction disruption of the donor heart in transmission electron microscopy during 4-h cold ischemia, improved myocardial reflow, and reduced microvascular leakage and cardiomyocyte injury of transplanted allografts during IRI. Concurrently, the treatment reduced expression of danger signals, dendritic cell maturation markers, endothelial cell adhesion molecule VCAM-1 and RhoA/Rho-associated protein kinase activation and the influx of macrophages and neutrophils. Furthermore, COMP-Ang1 treatment provided sustained anti-inflammatory effects during acute rejection and prevented the development of cardiac fibrosis and allograft vasculopathy. These results suggest donor heart treatment with COMP-Ang1 having important clinical implications in the prevention of primary and subsequent long-term injury and dysfunction in cardiac allografts. PMID:25932532

  17. Targeted disruption of the mouse adenine phosphoribosyltransferase (aprt) gene and the production of APRT-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Engle, S.J.; Chen, J.; Tischfield, J.A. [Indiana Univ., School of Medicine, Indianapolis, IN (United States)] [and others

    1994-09-01

    Adenine phosphoribosyltransferase (APRT: EC 2.4.2.7), a ubiquitously expressed purine salvage enzyme, catalyzes the synthesis of AMP and inorganic pyrophosphate from existing adenine and 5-phosphoribosyl-1-pyrophosphate. Deficiency of this enzyme in humans results in the accumulation of 2,8-dihydroxyadenine leading to crystalluria and nephrolithiasis. In order to facilitate our study of this rare, autosomal recessive disorder, we applied the advances in gene targeting technology and mouse embryonic stem (ES) cell culture to the production of APRT-deficient mice. A positive-negative targeting strategy was used. The tageting vector contain 5.6 kb of the mouse APRT gene, a neomycin resistance gene in exon 3 as a positive selection marker, and a HSV thymidine kinase gene at the 3{prime} end of the homology as a negative selection marker. The vector was introduced into D3 ES cells by electroporation and the cells were selected for G418 and ganciclovir (GANC) resistance. G418-GANC resistant clones were screened by Southern blot. One of several correctly targeted clones was expanded and used for blastocyst microinjection to produce chimeric mice. Chimeric animals were bred and agouti progeny heterozygous for the targeted allele were obtained. Heterozygous animals have been bred to produce APRT-deficient animals. Matings are currently underway to determine the phenotype of APRT/HPRT-deficient animals.

  18. A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss)

    KAUST Repository

    Khan, Uniza Wahid

    2016-07-04

    In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity.

  19. Modulation of leptin resistance by food compounds.

    Science.gov (United States)

    Aragonès, Gerard; Ardid-Ruiz, Andrea; Ibars, Maria; Suárez, Manuel; Bladé, Cinta

    2016-08-01

    Leptin is mainly secreted by white adipose tissue and regulates energy homeostasis by inhibiting food intake and stimulating energy expenditure through its action in neuronal circuits in the brain, particularly in the hypothalamus. However, hyperleptinemia coexists with the loss of responsiveness to leptin in common obese conditions. This phenomenon has been defined as leptin resistance and the restoration of leptin sensitivity is considered to be a useful strategy to treat obesity. This review summarizes the existing literature on potentially valuable nutrients and food components to reverse leptin resistance. Notably, several food compounds, such as teasaponins, resveratrol, celastrol, caffeine, and taurine among others, are able to restore the leptin signaling in neurons by overexpressing anorexigenic peptides (proopiomelanocortin) and/or repressing orexigenic peptides (neuropeptide Y/agouti-related peptide), thus decreasing food intake. Additionally, some nutrients, such as vitamins A and D, can improve leptin transport through the blood-brain barrier. Therefore, food components can improve leptin resistance by acting at different levels of the leptin pathway; moreover, some compounds are able to target more than one feature of leptin resistance. However, systematic studies are necessary to define the actual effectiveness of each compound. PMID:26842874

  20. Perinatal stress: characteristics and effects on adult eating behavior

    Directory of Open Access Journals (Sweden)

    Matilde Cesiana da Silva

    2013-08-01

    Full Text Available Many studies have pointed out the importance of mother-child interaction in the early months of life. A few decades ago, a method called kangaroo care was developed and its main goal was to keep underweight or premature newborns in direct contact with the mother. This method has reduced the morbidity and mortality of these newborns, increasing their growth rate, breastfeeding time and mother-child contact. In rodents, the dam's presence is crucial for avoiding aggression factors that may trigger phenotypic adaptations in the pups with irreversible morphological, functional and behavioral consequences. Eating behavior is an adaptive response stemming from the external environment demand and modulated by opportunities and limitations imposed by the external environment. This behavior is regulated by a complex interaction of peripheral and central mechanisms that control hunger and satiety. The hypothalamus is a brain structure that integrates central and peripheral signals to regulate energy homeostasis and body weight. The hypothalamic nucleus have orexigenic peptides, such as neuropeptide Y and the Agouti-related peptide, and anorexigenic peptides, such as cocaine and amphetamine regulated transcript and proopiomelanocortin. An innovative study of eating behavior in experimental models of neonatal stress separates the mother from the offspring during lactation. This review describes the effects of stress during the neonatal period on general physiological factors, particularly on the control of eating behavior.

  1. Hyper abundant mesopredators and bird extinction in an Atlantic forest island

    Directory of Open Access Journals (Sweden)

    Mauro Galetti

    2009-06-01

    Full Text Available Islands can serve as model systems for understanding how biological invasions affect native species. Here we examine the negative effects of mesopredator mammals on bird richness at Anchieta Island, an 826 ha offshore island in the coast of Brazil. Anchieta Island has the highest density of mammals of the entire Atlantic forest, especially nest predators such as marmosets and coatis, introduced more than 20 years ago. This indiscriminate introduction of mammals may have affected directly the bird community, nowadays represented by 100 species comprised mainly by water-crossing birds, being 73 forest-dwelling species. A small component of these remnant bird species nests in tree holes and on the forest floor, null model analysis suggest that birds within these two nest types are under-represented on Anchieta Island. All guilds were affected negatively, but "opportunist insectivorous/omnivorous". Experiments using artificial nests showed a predation of 73% of nests on the floor while only 26% on the mainland. Camera traps recorded predation by coatis, agoutis, and opossums. The restoration of the bird community on this island is highly constrained by the high density of hyper abundant nest predators.

  2. Role of copper accumulation in spontaneous renal carcinogenesis in Long-Evans Cinnamon rats.

    Science.gov (United States)

    Kitaura, K; Chone, Y; Satake, N; Akagi, A; Ohnishi, T; Suzuki, Y; Izumi, K

    1999-04-01

    Spontaneous renal cell tumors in totals of 223 male and female Long-Evans Cinnamon (LEC) rats of 51-120 weeks old, 157 male F344 rats of 51-120 weeks old, and 14 male Long-Evans Agouti (LEA) rats of 51-70 weeks old were examined histologically. The incidences of renal cell tumors increased with age in male and female LEC rats, but no tumors developed in F344 or LEA rats. Dilated atypical tubules of the kidneys were observed at high incidence in aged LEC rats. Copper staining of LEC rat kidneys showed a positive reaction in proximal tubules of the cortex and the outer stripe of the medulla. The renal copper concentration of LEC rats reached a peak in the period of necrotizing hepatitis with renal tubular necrosis, and was higher than that in F344 rats for up to 106 weeks. In contrast, the renal iron concentration of LEC rats was lower than that in F344 rats except in the period of necrotizing hepatitis. Long-term treatment of LEC rats with D-penicillamine, a copper-chelating agent, inhibited accumulation of copper, but not iron, in the kidneys, and inhibited the development of karyomegaly of proximal tubules and dilated atypical tubules. These results suggest that persistent copper accumulation after toxic necrosis of tubules is the major cause of spontaneous renal carcinogenesis in LEC rats.

  3. Leptin Induces Hypertension and Endothelial Dysfunction via Aldosterone-Dependent Mechanisms in Obese Female Mice.

    Science.gov (United States)

    Huby, Anne-Cécile; Otvos, Laszlo; Belin de Chantemèle, Eric J

    2016-05-01

    Obesity is a major risk factor for cardiovascular disease in males and females. Whether obesity triggers cardiovascular disease via similar mechanisms in both the sexes is, however, unknown. In males, the adipokine leptin highly contributes to obesity-related cardiovascular disease by increasing sympathetic activity. Females secrete 3× to 4× more leptin than males, but do not exhibit high sympathetic tone with obesity. Nevertheless, females show inappropriately high aldosterone levels that positively correlate with adiposity and blood pressure (BP). We hypothesized that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in females. Leptin control of the cardiovascular function was analyzed in female mice sensitized to leptin via the deletion of protein tyrosine phosphatase 1b (knockout) and in agouti yellow obese hyperleptinemic mice (Ay). Hypersensitivity to leptin (wild-type, 115 ± 2; protein tyrosine phosphatase 1b knockout, 124 ± 2 mm Hg; Phypertension and endothelial dysfunction via aldosterone-dependent mechanisms in female mice and suggest that obesity leads to cardiovascular disease via sex-specific mechanisms.

  4. Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Mark A. Smith

    2015-04-01

    Full Text Available Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC and agouti-related protein (AgRP neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons.

  5. A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss)

    Science.gov (United States)

    Khan, Uniza Wahid; Øverli, Øyvind; Hinkle, Patricia M.; Pasha, Farhan Ahmad; Johansen, Ida Beitnes; Berget, Ingunn; Silva, Patricia I. M.; Kittilsen, Silje; Höglund, Erik; Omholt, Stig W.; Våge, Dag Inge

    2016-01-01

    In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity. PMID:27373344

  6. A first genotyping assay of French cattle breeds based on a new allele of the extension gene encoding the melanocortin-1 receptor (Mc1r

    Directory of Open Access Journals (Sweden)

    Julien Raymond

    2000-09-01

    Full Text Available Abstract The seven transmembrane domain melanocortin-1 receptor (Mc1r encoded by the coat color extension gene (E plays a key role in the signaling pathway of melanin synthesis. Upon the binding of agonist (melanocortin hormone, α-MSH or antagonist (Agouti protein ligands, the melanosomal synthesis of eumelanin and/or phaeomelanin pigments is stimulated or inhibited, respectively. Different alleles of the extension gene were cloned from unrelated animals belonging to French cattle breeds and sequenced. The wild type E allele was mainly present in Normande cattle, the dominant ED allele in animals with black color (i.e. Holstein, whereas the recessive e allele was identified in homozygous animals exhibiting a more or less strong red coat color (Blonde d'Aquitaine, Charolaise, Limousine and Salers. A new allele, named E1, was found in either homozygous (E1/E1 or heterozygous (E1/E individuals in Aubrac and Gasconne breeds. This allele displayed a 4 amino acid duplication (12 nucleotides located within the third cytoplasmic loop of the receptor, a region known to interact with G proteins. A first genotyping assay of the main French cattle breeds is described based on these four extension alleles.

  7. Ex vivo intracoronary gene transfer of adeno-associated virus 2 leads to superior transduction over serotypes 8 and 9 in rat heart transplants.

    Science.gov (United States)

    Raissadati, Alireza; Jokinen, Janne J; Syrjälä, Simo O; Keränen, Mikko A I; Krebs, Rainer; Tuuminen, Raimo; Arnaudova, Ralica; Rouvinen, Eeva; Anisimov, Andrey; Soronen, Jarkko; Pajusola, Katri; Alitalo, Kari; Nykänen, Antti I; Lemström, Karl

    2013-11-01

    Heart transplant gene therapy requires vectors with long-lasting gene expression, high cardiotropism, and minimal pathological effects. Here, we examined transduction properties of ex vivo intracoronary delivery of adeno-associated virus (AAV) serotype 2, 8, and 9 in rat syngenic and allogenic heart transplants. Adult Dark Agouti (DA) rat hearts were intracoronarily perfused ex vivo with AAV2, AAV8, or AAV9 encoding firefly luciferase and transplanted heterotopically into the abdomen of syngenic DA or allogenic Wistar-Furth (WF) recipients. Serial in vivo bioluminescent imaging of syngraft and allograft recipients was performed for 6 months and 4 weeks, respectively. Grafts were removed for PCR-, RT-PCR, and luminometer analysis. In vivo bioluminescent imaging of recipients showed that AAV9 induced a prominent and stable luciferase activity in the abdomen, when compared with AAV2 and AAV8. However, ex vivo analyses revealed that intracoronary perfusion with AAV2 resulted in the highest heart transplant transduction levels in syngrafts and allografts. Ex vivo intracoronary delivery of AAV2 resulted in efficient transgene expression in heart transplants, whereas intracoronary AAV9 escapes into adjacent tissues. In terms of cardiac transduction, these results suggest AAV2 as a potential vector for gene therapy in preclinical heart transplants studies, and highlight the importance of delivery route in gene transfer studies.

  8. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control

    Science.gov (United States)

    Yan, Ai-Fen; Chen, Ting; Chen, Shuang; Ren, Chun-Hua; Hu, Chao-Qun; Cai, Yi-Ming; Liu, Fang; Tang, Dong-Sheng

    2016-01-01

    In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model. PMID:27249000

  9. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control.

    Science.gov (United States)

    Yan, Ai-Fen; Chen, Ting; Chen, Shuang; Ren, Chun-Hua; Hu, Chao-Qun; Cai, Yi-Ming; Liu, Fang; Tang, Dong-Sheng

    2016-01-01

    In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model. PMID:27249000

  10. A 6-bp deletion in exon 8 and two mutations in introns of TYRP1 are associated with blond coat color in Liangshan pigs.

    Science.gov (United States)

    Wu, Xiaoqian; Zhang, Yi; Shen, Linyuan; Du, Jingjing; Luo, Jia; Liu, Chendong; Pu, Qiang; Yang, Runlin; Li, Xuewei; Bai, Lin; Tang, Guoqing; Zhang, Shunhua; Zhu, Li

    2016-03-01

    Melanocortin receptor 1 (MC1R), Agouti signaling protein (ASIP), and Tyrosinase-related protein 1 (TYRP1) are reported critical genes that regulate pheomelanin and eumelanin synthesis in mammals. Liangshan pig is a special Chinese indigenous pig breed with two completely different coat colors, solid black and blond. In this study, we detected polymorphisms of the above three genes and assessed the relationships between the variations and coat color phenotypes in Liangshan pigs. The findings revealed that the blond phenotype of Liangshan pig was related to dominant mutations in TYRP1, but not related to mutations in MC1R or ASIP. We found three closely linked mutations in TYRP1, g.8406G>A in intron 4, g.11100A>G in intron 5, and g.17599_17604del in exon 8, that were completely associated with blond coat color in Liangshan pigs. Further analysis revealed that a 6-bp deletion mutation resulted in deletion of Met and Gly residues at positions 495 and 496 in TYRP1 protein, and altered the structure of transmembrane domain of TYRP1. Together, our findings indicated that these three mutations in TYRP1 cause the blond phenotype in Liangshan pigs. PMID:26680103

  11. Melanocortin 1 Receptor: Structure, Function, and Regulation

    Science.gov (United States)

    Wolf Horrell, Erin M.; Boulanger, Mary C.; D’Orazio, John A.

    2016-01-01

    The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair (NER), the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts NER. PMID:27303435

  12. Plasticity of the melanocortin system: determinants and possible consequences on food intake

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    Danaé eNuzzaci

    2015-09-01

    Full Text Available The melanocortin system is one of the most important neuronal pathways involved in the regulation of food intake and is probably the best characterized. Agouti-related peptide (AgRP and proopiomelanocortin (POMC expressing neurons located in the arcuate nucleus of the hypothalamus are key elements of this system. These two neuronal populations are sensitive to circulating molecules and receive many excitatory and inhibitory inputs from various brain areas. According to sensory and metabolic information they integrate, these neurons control different aspects of feeding behavior and orchestrate autonomic responses aimed at maintaining energy homeostasis. Interestingly, composition and abundance of pre-synaptic inputs onto arcuate AgRP and POMC neurons vary in the adult hypothalamus in response to changes in the metabolic state, a phenomenon that can be recapitulated by treatment with hormones such as leptin or ghrelin. As described in other neuroendrocrine systems, glia might be determinant to shift the synaptic configuration of AgRP and POMC neurons. Here, we discuss the physiological outcome of the synaptic plasticity of the melanocortin system, and more particularly its contribution to the control of energy balance. The discovery of this attribute has changed how we view obesity and related disorders, and opens new perspectives for their management.

  13. Melanocortin 1 Receptor: Structure, Function and Regulation

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    Erin Marissa Wolf Horrell

    2016-05-01

    Full Text Available The melanocortin 1 receptor (MC1R is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair, the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts nucleotide excision repair.

  14. Effects of hypothalamic neurodegeneration on energy balance.

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    Allison Wanting Xu

    2005-12-01

    Full Text Available Normal aging in humans and rodents is accompanied by a progressive increase in adiposity. To investigate the role of hypothalamic neuronal circuits in this process, we used a Cre-lox strategy to create mice with specific and progressive degeneration of hypothalamic neurons that express agouti-related protein (Agrp or proopiomelanocortin (Pomc, neuropeptides that promote positive or negative energy balance, respectively, through their opposing effects on melanocortin receptor signaling. In previous studies, Pomc mutant mice became obese, but Agrp mutant mice were surprisingly normal, suggesting potential compensation by neuronal circuits or genetic redundancy. Here we find that Pomc-ablation mice develop obesity similar to that described for Pomc knockout mice, but also exhibit defects in compensatory hyperphagia similar to what occurs during normal aging. Agrp-ablation female mice exhibit reduced adiposity with normal compensatory hyperphagia, while animals ablated for both Pomc and Agrp neurons exhibit an additive interaction phenotype. These findings provide new insight into the roles of hypothalamic neurons in energy balance regulation, and provide a model for understanding defects in human energy balance associated with neurodegeneration and aging.

  15. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    Science.gov (United States)

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes. PMID:26467632

  16. Neuroendorine and Epigentic Mechanisms Subserving Autonomic Imbalance and HPA Dysfunction in the Metabolic Syndrome

    Science.gov (United States)

    Lemche, Erwin; Chaban, Oleg S.; Lemche, Alexandra V.

    2016-01-01

    Impact of environmental stress upon pathophysiology of the metabolic syndrome (MetS) has been substantiated by epidemiological, psychophysiological, and endocrinological studies. This review discusses recent advances in the understanding of causative roles of nutritional factors, sympathomedullo-adrenal (SMA) and hypothalamic-pituitary adrenocortical (HPA) axes, and adipose tissue chronic low-grade inflammation processes in MetS. Disturbances in the neuroendocrine systems for leptin, melanocortin, and neuropeptide Y (NPY)/agouti-related protein systems have been found resulting directly in MetS-like conditions. The review identifies candidate risk genes from factors shown critical for the functioning of each of these neuroendocrine signaling cascades. In its meta-analytic part, recent studies in epigenetic modification (histone methylation, acetylation, phosphorylation, ubiquitination) and posttranscriptional gene regulation by microRNAs are evaluated. Several studies suggest modification mechanisms of early life stress (ELS) and diet-induced obesity (DIO) programming in the hypothalamic regions with populations of POMC-expressing neurons. Epigenetic modifications were found in cortisol (here HSD11B1 expression), melanocortin, leptin, NPY, and adiponectin genes. With respect to adiposity genes, epigenetic modifications were documented for fat mass gene cluster APOA1/C3/A4/A5, and the lipolysis gene LIPE. With regard to inflammatory, immune and subcellular metabolism, PPARG, NKBF1, TNFA, TCF7C2, and those genes expressing cytochrome P450 family enzymes involved in steroidogenesis and in hepatic lipoproteins were documented for epigenetic modifications. PMID:27147943

  17. A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Khan, Uniza Wahid; Øverli, Øyvind; Hinkle, Patricia M; Pasha, Farhan Ahmad; Johansen, Ida Beitnes; Berget, Ingunn; Silva, Patricia I M; Kittilsen, Silje; Höglund, Erik; Omholt, Stig W; Våge, Dag Inge

    2016-01-01

    In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity. PMID:27373344

  18. Proliferation of CD8-positive T cells in blood vessels of rat renal allografts.

    Science.gov (United States)

    Grau, V; Fuchs-Moll, G; Wilker, S; Weimer, R; Padberg, W

    2011-09-01

    It is still disputed in which anatomical compartments of allograft recipients T-cells proliferate. After experimental renal transplantation, host monocytes and lymphocytes accumulate in the lumina of graft blood vessels. In this study, we test the hypothesis that T lymphocytes proliferate in the vascular bed of the graft. Kidneys were transplanted in the Dark Agouti to Lewis rat strain combination, an established experimental model for acute rejection. Isogeneic transplantation was performed as a control. Cells in the S-phase of mitosis were detected in situ three days posttransplantation by pulse-labeling with BrdU and by immunohistochemical detection of the proliferating cell nuclear antigen (PCNA). More than 20% of all T-cells in the lumina of allograft blood vessels incorporated BrdU and approximately 30% of them expressed PCNA. In the blood vessels of isografts as well as in other organs of allograft recipients, only few BrdU(+) cells were detected. A majority of the BrdU(+) cells in graft blood vessels expressed CD8. In conclusion, we demonstrate that CD8(+) T lymphocytes proliferate in the lumina of the blood vessels of renal allografts during the onset of acute rejection.

  19. [The genetic control of mouse coat color and its applications in genetics teaching].

    Science.gov (United States)

    Xing, Wanjin; Morigen, Morigen

    2014-10-01

    Mice are the most commonly used mammalian model. The coat colors of mice are typical Mendelian traits, which have various colors such as white, black, yellow and agouti. The inheritance of mouse coat color is usually stated as an example only in teaching the knowledge of recessive lethal alleles. After searched the related literatures and summarized the molecular mechanisms of mouse coat color inheritance, we further expanded the application of this example into the introduction of the basic concepts of alleles and Mendelian laws, demonstration of the gene structure and function, regulation of gene expression, gene interaction, epigenetic modification, quantitative genetics, as well as evolutionary genetics. By running this example through the whole genetics-teaching lectures, we help the student to form a systemic and developmental view of genetic analysis. At the same time, this teaching approach not only highlights the advancement and integrity of genetics, but also results in a good teaching effect on inspiring the students' interest and attracting students' attention.

  20. Partial lesion of the serotonergic system by a single dose of MDMA results in behavioural disinhibition and enhances acute MDMA-induced social behaviour on the social interaction test.

    Science.gov (United States)

    Ando, Romeo D; Benko, Anita; Ferrington, Linda; Kirilly, Eszter; Kelly, Paul A T; Bagdy, Gyorgy

    2006-06-01

    The acute effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) on anxiety-related behaviours were studied using indices of social interaction in Dark Agouti (DA) both drug naive rats and those pretreated with MDMA (15 mg/kg i.p.) 3 weeks earlier. The functional neuroanatomy of these MDMA effects was visualised using 2-deoxyglucose imaging of local cerebral glucose use (LCMRglu), whilst MDMA-induced serotonergic neurotoxicity was measured by radioligand binding with [3H]paroxetine. Acute MDMA alone markedly decreased most typical elements of social interaction but increased adjacent lying, a behaviour that also contains social elements. In animals pre-exposed to MDMA, decreased [3H]paroxetine binding indicated serotonergic terminal depletion, and in these animals significant increases in locomotor activity, exploratory behaviour and aggressive behaviour were found. Both behavioural effects and also the metabolic activation induced by acute MDMA were potentiated in rats previously exposed to the drug. In conclusion, a single dose of MDMA caused marked changes in social behaviour acutely that might be interpreted either as a decrease or increase in anxiety. Three weeks after MDMA a behavioural disinhibition similar to psychomotor agitation, a symptom connected to depression or mania, and a sensitization to the acute effects of MDMA are apparent in both the behavioural and brain metabolic effects of the drug.

  1. Peptides: Basic determinants of reproductive functions.

    Science.gov (United States)

    Celik, Onder; Aydin, Suleyman; Celik, Nilufer; Yilmaz, Musa

    2015-10-01

    Mammalian reproduction is a costly process in terms of energy consumption. The critical information regarding metabolic status is signaled to the hypothalamus mainly through peripheral peptides from the adipose tissue and gastrointestinal tract. Changes in energy stores produce fluctuations in leptin, insulin, ghrelin and glucose signals that feedback mainly to the hypothalamus to regulate metabolism and fertility. In near future, possible effects of the nutritional status on GnRH regulation can be evaluated by measuring serum or tissue levels of leptin and ghrelin in patiens suffering from infertility. The fact that leptin and ghrelin are antagonistic in their effects on GnRH neurons, their respective agonistic and antagonistic roles make them ideal candidates to use instead of GnRH agonist and antagonist. Similarly, kisspeptin expressing neurons are likely to mediate the well-established link between energy balance and reproductive functions. Exogenous kisspeptin can be used for physiological ovarian hyperstimulation for in-vitro fertilization. Moreover, kisspeptin antagonist therapy can be used for the treatment of postmenapousal women, precocious puberty, PCOS, endometriosis and uterine fibroids. In this review, we will analyze the central mechanisms involved in the integration of metabolic information and their contribution to the control of the reproductive function. Particular attention will be paid to summarize the participation of leptin, kisspeptin, ghrelin, NPY, orexin, urocortin, VIP, insulin, galanin, galanin like peptide, oxytocin, agouti gene-related peptide, and POMC neurons in this process and their possible interactions to contribute to the metabolic control of reproduction. PMID:26074346

  2. Glutamate and GABA as rapid effectors of hypothalamic peptidergic neurons

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    Cornelia eSchöne

    2012-11-01

    Full Text Available Vital hypothalamic neurons regulating hunger, wakefulness, reward-seeking, and body weight are often defined by unique expression of hypothalamus-specific neuropeptides. Gene-ablation studies show that some of these peptides, notably orexin/hypocretin (hcrt/orx, are themselves critical for stable states of consciousness and metabolic health. However, neuron-ablation studies often reveal more severe phenotypes, suggesting key roles for co-expressed transmitters. Indeed, most hypothalamic neurons, including hcrt/orx cells, contain fast transmitters glutamate and GABA, as well as several neuropeptides. What are the roles and relations between different transmitters expressed by the same neuron? Here, we consider signaling codes for releasing different transmitters in relation to transmitter and receptor diversity in behaviorally-defined, widely-projecting peptidergic neurons, such as hcrt/orx cells. We then discuss latest optogenetic studies of endogenous transmitter release from defined sets of axons in situ, which suggest that recently-characterized vital peptidergic neurons (e.g. hcrt/orx, proopiomelanocortin , and agouti-related peptide cells, as well as classical modulatory neurons (e.g. dopamine and acetylcholine cells, all use fast transmitters to control their postsynaptic targets. These optogenetic insights are complemented by recent observations of behavioral deficiencies caused by genetic ablation of fast transmission from specific neuropeptidergic and aminergic neurons. Powerful and fast (millisecond-scale GABAergic and glutamatergic signaling from neurons previously considered to be primarily modulatory raises new questions about the roles of slower co-transmitters they co-express.

  3. Anatomic aspects of the male genital organs of adult galea (Galea spixii Wagler, 1831

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    Maria Angelica Miglino

    2013-03-01

    Full Text Available The Galea spixii are hystricomorpha with reproductive and feeding activity subject to rainfall and climatic factors. Due to lack of knowledge on the reproductive system in Galea this study aimed to describe its macroscopic anatomy and topography. Ten adult animals from the Centre for Wild Animals Multiplication of Universidade Federal Rural do Semiarido were used. Then, dissections, photographs, and in situ organ description in order to better preserve topography. The male genitalia were represented by the testes, epididymis, accessory genital glands (represented by the prostate and the vesicular and bulbourethral glands, besides penis and scrotum. The testes were ovoid and located at different sites, depending on the animal’s reproductive activity. The epididymis had three regions: head, body, and tail. The prostate was divided into two lateral portions, with two lobes. The penis was cylindrical and it had a cranial flexure, bending it caudally. The gland was lined by a rough epithelium, keratinized with superficial spicules. The findings described for the male reproductive system of the Galea are similar to those described for rodents like the agouti and rock cavy, especially with regard to testicular gross anatomy, penis shape, and presence of spicules in the glands.

  4. Recurrent evolution of melanism in South American felids.

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    Alexsandra Schneider

    2015-02-01

    Full Text Available Morphological variation in natural populations is a genomic test bed for studying the interface between molecular evolution and population genetics, but some of the most interesting questions involve non-model organisms that lack well annotated reference genomes. Many felid species exhibit polymorphism for melanism but the relative roles played by genetic drift, natural selection, and interspecies hybridization remain uncertain. We identify mutations of Agouti signaling protein (ASIP or the Melanocortin 1 receptor (MC1R as independent causes of melanism in three closely related South American species: the pampas cat (Leopardus colocolo, the kodkod (Leopardus guigna, and Geoffroy's cat (Leopardus geoffroyi. To assess population level variation in the regions surrounding the causative mutations we apply genomic resources from the domestic cat to carry out clone-based capture and targeted resequencing of 299 kb and 251 kb segments that contain ASIP and MC1R, respectively, from 54 individuals (13-21 per species, achieving enrichment of ~500-2500-fold and ~150x coverage. Our analysis points to unique evolutionary histories for each of the three species, with a strong selective sweep in the pampas cat, a distinctive but short melanism-specific haplotype in the Geoffroy's cat, and reduced nucleotide diversity for both ancestral and melanism-bearing chromosomes in the kodkod. These results reveal an important role for natural selection in a trait of longstanding interest to ecologists, geneticists, and the lay community, and provide a platform for comparative studies of morphological variation in other natural populations.

  5. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    International Nuclear Information System (INIS)

    Highlights: → The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. → The level of colocalization is similar in the male and female brain. → Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. → Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  6. Arcuate AgRP neurons and the regulation of energy balance

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    Céline eCansell

    2012-12-01

    Full Text Available The arcuate nucleus of the hypothalamus contains at least two crucial populations of neurons that continuously monitor signals reflecting energy status and promote the appropriate behavioral and metabolic responses to changes in energy demand. Neurons making pro-opiomelanocortin (POMC decrease food intake and increase energy expenditure through activation of G protein-coupled receptors melanocortin receptors (MCR via the release of a-melanocyte stimulating hormone. A prevailing idea until recently was that the neighboring neurons expressing the orexigenic neuropeptides, agouti-related protein (AgRP and neuropeptide Y (NPY (AgRP neurons increased feeding by opposing the anorexigenic actions of the POMC neurons. AgRP neurons activation but not POMC neurons inhibition was recently demonstrated to be necessary and sufficient to promote feeding. AgRP expressing axons were identified in mesolimbic, midbrain and pontine structure where they regulate feeding but also feeding-independent functions such as reward or peripheral nutrient partitioning. Post-synaptic Gamma aminobutyric acid (GABA, lasting in a timeline similar to neuromodulation, was identified as the core mechanism by which hunger-activated neurons regulate feeding and non-food related processes in a melanocortin independent manner.

  7. Transgenic n-3 PUFAs enrichment leads to weight loss via modulating neuropeptides in hypothalamus.

    Science.gov (United States)

    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.

  8. Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

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    Allison eGraebner

    2015-08-01

    Full Text Available A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools have greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

  9. Neuropeptide co-expression in hypothalamic kisspeptin neurons of laboratory animals and the human

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    Katalin eSkrapits

    2015-02-01

    Full Text Available 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 species. 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.

  10. Expression profile of hypothalamic neuropeptides in chicken lines selected for high or low residual feed intake.

    Science.gov (United States)

    Sintubin, P; Greene, E; Collin, A; Bordas, A; Zerjal, T; Tesseraud, S; Buyse, J; Dridi, S

    2014-08-01

    The R(+) and R(-) chicken lines have been divergently selected for high (R(+)) or low (R(-)) residual feed intake. For the same body weight and egg production, the R(+) chickens consume 40% more food than their counterparts R(-) lines. In the present study we sought to determine the hypothalamic expression profile of feeding-related neuropeptides in these lines maintained under fed or food-deprived conditions. In the fed condition, the suppressor of cytokine signaling 3 (SOCS3) was 17-fold lower (Pneuropeptide Y and agouti-related peptide were more responsive, with higher significant levels in the R(+) compared to R(-) chickens, while no significant differences were seen for the anorexigenic neuropeptides pro-opiomelanocortin and corticotropin releasing hormone. Interestingly, C-reactive protein, adiponectin receptor 1 and ghrelin receptor gene expression were significantly higher (12-, 2- and 3-folds, respectively), however ghrelin and melanocortin 5 receptor mRNA levels were lower (4- and 2-folds, P=0.05 and P=0.03, respectively) in R(+) compared to R(-) animals. We identified several key feeding-related genes that are differently expressed in the hypothalamus of R(+) and R(-) chickens and that might explain the difference in feed intake observed between the two lines.

  11. Hypothalamic neuropeptides and the regulation of appetite.

    Science.gov (United States)

    Parker, Jennifer A; Bloom, Stephen R

    2012-07-01

    Neuropeptides released by hypothalamic neurons play a major role in the regulation of feeding, acting both within the hypothalamus, and at other appetite regulating centres throughout the brain. Where classical neurotransmitters signal only within synapses, neuropeptides diffuse over greater distances affecting both nearby and distant neurons expressing the relevant receptors, which are often extrasynaptic. As well as triggering a behavioural output, neuropeptides also act as neuromodulators: altering the response of neurons to both neurotransmitters and circulating signals of nutrient status. The mechanisms of action of hypothalamic neuropeptides with established roles in feeding, including melanin-concentrating hormone (MCH), the orexins, α-melanocyte stimulating hormone (α-MSH), agouti-gene related protein (AgRP), neuropeptide Y, and oxytocin, are reviewed in this article, with emphasis laid on both their effects on appetite regulating centres throughout the brain, and on examining the evidence for their physiological roles. In addition, evidence for the involvement of several putative appetite regulating hypothalamic neuropeptides is assessed including, ghrelin, cocaine and amphetamine-regulated transcript (CART), neuropeptide W and the galanin-like peptides. This article is part of a Special Issue entitled 'Central control of Food Intake'.

  12. Feeding behavior and gene expression of appetite-related neuropeptides in mice lacking for neuropeptide Y Y5 receptor subclass

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Higuchi; Takeshi Nild; Tomohiro Shiiya

    2008-01-01

    Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexi-genic neuropeptides such as a-melatonin stimulating hormone (MSH) and cocaine-amphetamine-regulated transcript (CART) are also involved in central feeding regulation. During fasting, NPY and AgRP gene expres-sions are up-regulated and POMC and CART gene ex-pressions are down-regulated in hypothalamus. Based on the network of peptidergic neurons, the former are involved in positive feeding regulation, and the latter are involved in negative feeding, which exert these feeding-regulated peptides especially in paraventricular nucleus (PVN). To clarify the compensatory mecha-nism of knock-out of NPY system on feeding, change in gene expressions of appetite-related neuropeptides and the feeding behavior was studied in NPY Y5-KO mice. Food intake was increased in Y5-KO mice. Fast-ing increased the amounts of food and water intake in the KO mice more profoundly. These data indicated the compensatory phenomenon of feeding behavior in YS-KO mice. RT-PCR and [SH suggested that the compensation of feeding is due to change in gene ex-pressions of AgRP, CART and POMC in hypothalamus. Thus, these findings indicated that the compensatory mechanism involves change in POMC/CART gene ex-pression in arcuate nucleus (ARC). The POMC/CART gene expression is important for central compensatory regulation in feeding behavior.

  13. The functional requirements of mammalian hair: a compromise between crypsis and thermoregulation?

    Science.gov (United States)

    Wacker, Chris B.; McAllan, Bronwyn M.; Körtner, Gerhard; Geiser, Fritz

    2016-08-01

    Mammalian fur often shows agouti banding with a proximal dark band near the skin and a lighter distal band. We examined the function of both bands in relation to camouflage, thermal properties of pelts, and thermal energetics of dunnarts ( Sminthopsis crassicaudata), which are known to use torpor and basking. Although the distal band of dunnart fur darkened with increasing latitude, which is important for camouflage, it did not affect the thermal properties and the length of the dark band and total hair length were not correlated. In contrast, the length of the proximal dark band of preserved pelts exposed to sunlight was positively correlated ( r 2 = 0.59) with the temperature underneath the pelt ( T pelt). All dunnarts offered radiant heat basked by exposing the dark band of the hair during both rest and torpor. Basking dunnarts with longer dark bands had lower resting metabolism ( r 2 = 0.69), warmed faster from torpor ( r 2 = 0.77), required less energy to do so ( r 2 = 0.32), and reached a higher subcutaneous temperature ( T sub) at the end of rewarming ( r 2 = 0.75). We provide the first experimental evidence on the possible dual function of the color banding of mammalian fur. The distal colored band appears to be important for camouflage, whereas the length of the dark proximal hair band facilitates heat gain for energy conservation and allows animals to rewarm quickly and economically from torpor.

  14. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Pawel K., E-mail: olsze005@umn.edu [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Fredriksson, Robert; Eriksson, Jenny D. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Mitra, Anaya [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Radomska, Katarzyna J. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Gosnell, Blake A. [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Solvang, Maria N. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Levine, Allen S. [Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Schioeth, Helgi B. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden)

    2011-05-13

    Highlights: {yields} The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. {yields} The level of colocalization is similar in the male and female brain. {yields} Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. {yields} Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  15. Energy Balance Regulating Neuropeptides Are Expressed through Pregnancy and Regulated by Interleukin-6 Deficiency in Mouse Placenta

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    Patricia Pazos

    2014-01-01

    Full Text Available The placenta produces a number of signaling molecules including metabolic and reproductive hormones as well as several inflammatory mediators. Among them, Interleukin-6 (IL-6, a well-known immune and metabolic regulator, acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. IL-6 interacts with key hypothalamic neuropeptidergic systems controlling energy homeostasis such as those producing the orexigenic/anabolic: neuropeptide Y (NPY and agouti-related peptide (AgRP and anorectic/catabolic neuropeptides: proopiomelanocortin (POMC and cocaine and amphetamine regulated transcript (CART. Human and rat placenta have been identified as source of these neuropeptides, but their expression and regulation in murine placental tissues remain unknown. Therefore, placental mRNA levels of IL-6, NPY, AgRP, POMC, and CART at different pregnancy stages (gestational days 13, 15, and 18 were analyzed by real time PCR, as were the effect of IL-6 deficiency (IL-6 knockout mice on their placental expression. Our results showed that placenta-derived neuropeptides were regulated by gestational age and IL-6 throughout the second half of mouse pregnancy. These data suggest that IL-6 may participate in the fine tune control of energy balance during pregnancy by extending its action as a metabolic signal to the main organ at the fetomaternal interface: the placenta.

  16. Direct modulation of GFAP-expressing glia in the arcuate nucleus bi-directionally regulates feeding

    Science.gov (United States)

    Chen, Naiyan; Barak, Boaz; Sur, Mriganka

    2016-01-01

    Multiple hypothalamic neuronal populations that regulate energy balance have been identified. Although hypothalamic glia exist in abundance and form intimate structural connections with neurons, their roles in energy homeostasis are less known. Here we show that selective Ca2+ activation of glia in the mouse arcuate nucleus (ARC) reversibly induces increased food intake while disruption of Ca2+ signaling pathway in ARC glia reduces food intake. The specific activation of ARC glia enhances the activity of agouti-related protein/neuropeptide Y (AgRP/NPY)-expressing neurons but induces no net response in pro-opiomelanocortin (POMC)-expressing neurons. ARC glial activation non-specifically depolarizes both AgRP/NPY and POMC neurons but a strong inhibitory input to POMC neurons balances the excitation. When AgRP/NPY neurons are inactivated, ARC glial activation fails to evoke any significant changes in food intake. Collectively, these results reveal an important role of ARC glia in the regulation of energy homeostasis through its interaction with distinct neuronal subtype-specific pathways. DOI: http://dx.doi.org/10.7554/eLife.18716.001 PMID:27751234

  17. A new species of Callicebus Thomas, 1903 (Primates, Pitheciidae from the states of Mato Grosso and Pará, Brazil

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    Juliana Gualda-Barros

    2012-01-01

    Full Text Available A new species of titi monkey, genus Callicebus Thomas, 1903, is described based on four individuals, one from a small tributary of the left bank of Rio Teles Pires, northern state of Mato Grosso, and three others from Largo do Souza, Rio Iriri, Pará, Brazil. The new species belongs to the Callicebus moloch species group, and the main diagnostic characteristics of the new species are the whitish forehead, sideburns and beard coloration, which are contiguous, forming a frame around the blackish face; overall body pelage coloration is pale grayish-brown agouti; hands, feet and tip of the tail whitish; belly and inner sides of fore and hind limbs uniformly orange. The pattern of pelage coloration and qualitative and quantitative skull morphology are described and compared to the other species of the Callicebus moloch group. Species of the Callicebus moloch group show great similarity in skull morphology and morphometrics, making the external morphological characters, specially the chromatic fields, the most reliable diagnostic trait to identify the species.

  18. [The interconnections of molecular mechanisms of hormone actions and their role in pathogenesis of obesity, insulin resistance, and diabetes mellitus].

    Science.gov (United States)

    Pankov, Iu A; Chekhranova, M K; Karpova, S K

    2008-01-01

    The various hormones, proteins and other compounds related to developing obesity, insulin resistance and type 2 diabetes are analyzed in the paper. 1) Leptin, ciliary neurutrophic factor, adiponectin, glucagon-like peptide 1, peptide YY, neuromedin S, as well as the protein receptors of these hormones decrease the food consumption, increase the energy turnover, and prevent obesity, insulin resistance, and type 2 diabetes development. The mediators of these hormone and receptor actions are melanocyte stimulating hormone (MSH), corticotropin-releasing hormone (CRH), and the others. 2) Ghrelin, endogenose cannabinoides, galanin-like peptide and the mediators of their actions: neuropeptide Y (NPY) and Agouti gene related protein (AGRP) increase the appetite and food consumption. Peroxisome proliferation-activated receptor (PPAR) performs the similar action on food intake. The activation of the first group compound functioning decreases the obesity, increases the energy turnover, facilitates the insulin action and prevents the insulin resistance and type 2 diabetes. Increasing the activities of the second group, as well as, decreasing the actions of the first one of substances induce the opposite effects and facilitate obesity, insulin resistance, and type 2 diabetes developments. The interconnections of the molecular mechanisms of so many hormone actions make the very complicated tusk to study the various endocrine disorders including diabetes mellitus as well.

  19. Signature of balancing selection at the MC1R gene in Kunming dog populations.

    Directory of Open Access Journals (Sweden)

    Guo-dong Wang

    Full Text Available Coat color in dog breeds is an excellent character for revealing the power of artificial selection, as it is extremely diverse and likely the result of recent domestication. Coat color is generated by melanocytes, which synthesize pheomelanin (a red or yellow pigment or eumelanin (a black or brown pigment through the pigment type-switching pathway, and is regulated by three genes in dogs: MC1R (melanocortin receptor 1, CBD103 (β-defensin 103, and ASIP (agouti-signaling protein precursor. The genotypes of these three gene loci in dog breeds are associated with coat color pattern. Here, we resequenced these three gene loci in two Kunming dog populations and analyzed these sequences using population genetic approaches to identify evolutionary patterns that have occurred at these loci during the recent domestication and breeding of the Kunming dog. The analysis showed that MC1R undergoes balancing selection in both Kunming dog populations, and that the Fst value for MC1R indicates significant genetic differentiation across the two populations. In contrast, similar results were not observed for CBD103 or ASIP. These results suggest that high heterozygosity and allelic differences at the MC1R locus may explain both the mixed color coat, of yellow and black, and the difference in coat colors in both Kunming dog populations.

  20. Acute heat stress up-regulates neuropeptide Y precursor mRNA expression and alters brain and plasma concentrations of free amino acids in chicks.

    Science.gov (United States)

    Ito, Kentaro; Bahry, Mohammad A; Hui, Yang; Furuse, Mitsuhiro; Chowdhury, Vishwajit S

    2015-09-01

    Heat stress causes an increase in body temperature and reduced food intake in chickens. Several neuropeptides and amino acids play a vital role in the regulation of food intake. However, the responses of neuropeptides and amino acids to heat-stress-induced food-intake regulation are poorly understood. In the current study, the hypothalamic mRNA expression of some neuropeptides related to food intake and the content of free amino acids in the brain and plasma was examined in 14-day-old chicks exposed to a high ambient temperature (HT; 40±1 °C for 2 or 5 h) or to a control thermoneutral temperature (CT; 30±1 °C). HT significantly increased rectal temperature and plasma corticosterone level and suppressed food intake. HT also increased the expression of neuropeptide Y (NPY) and agouti-signaling protein (ASIP) precursor mRNA, while no change was observed in pro-opiomelanocortin, cholecystokinin, ghrelin, or corticotropin-releasing hormone precursor mRNA. It was further found that the diencephalic content of free amino acids - namely, tryptophan, leucine, isoleucine, valine and serine - was significantly higher in HT chicks with some alterations in their plasma amino acids in comparison with CT chicks. The induction of NPY and ASIP expression and the alteration of some free amino acids during HT suggest that these changes can be the results or causes the suppression of food intake.

  1. Control of energy balance by hypothalamic gene circuitry involving two nuclear receptors, neuron-derived orphan receptor 1 and glucocorticoid receptor.

    Science.gov (United States)

    Kim, Sun-Gyun; Lee, Bora; Kim, Dae-Hwan; Kim, Juhee; Lee, Seunghee; Lee, Soo-Kyung; Lee, Jae W

    2013-10-01

    Nuclear receptors (NRs) regulate diverse physiological processes, including the central nervous system control of energy balance. However, the molecular mechanisms for the central actions of NRs in energy balance remain relatively poorly defined. Here we report a hypothalamic gene network involving two NRs, neuron-derived orphan receptor 1 (NOR1) and glucocorticoid receptor (GR), which directs the regulated expression of orexigenic neuropeptides agouti-related peptide (AgRP) and neuropeptide Y (NPY) in response to peripheral signals. Our results suggest that the anorexigenic signal leptin induces NOR1 expression likely via the transcription factor cyclic AMP response element-binding protein (CREB), while the orexigenic signal glucocorticoid mobilizes GR to inhibit NOR1 expression by antagonizing the action of CREB. Also, NOR1 suppresses glucocorticoid-dependent expression of AgRP and NPY. Consistently, relative to wild-type mice, NOR1-null mice showed significantly higher levels of AgRP and NPY and were less responsive to leptin in decreasing the expression of AgRP and NPY. These results identify mutual antagonism between NOR1 and GR to be a key rheostat for peripheral metabolic signals to centrally control energy balance.

  2. Interactions between SNP Alleles at Multiple Loci Contribute to Skin Color Differences between Caucasoid and Mongoloid Subjects

    Directory of Open Access Journals (Sweden)

    Sumiko Anno, Takashi Abe, Takushi Yamamoto

    2008-01-01

    Full Text Available This study aimed to identify single nucleotide polymorphism (SNP alleles at multiple loci associated with racial differences in skin color using SNP genotyping. A total of 122 Caucasians in Toledo, Ohio and 100 Mongoloids in Japan were genotyped for 20 SNPs in 7 candidate genes, encoding the Agouti signaling protein (ASIP, tyrosinase-related protein 1 (TYRP1, tyrosinase (TYR, melanocortin 1 receptor (MC1R, oculocutaneous albinism II (OCA2, microphthalmia-associated transcription factor (MITF, and myosin VA (MYO5A. Data were used to analyze associations between the 20 SNP alleles using linkage disequilibrium (LD. Combinations of SNP alleles were jointly tested under LD for associations with racial groups by performing a χ2 test for independence. Results showed that SNP alleles at multiple loci can be considered the haplotype that contributes to significant differences between the two population groups and suggest a high probability of LD. Confirmation of these findings requires further study with other ethnic groups to analyze the associations between SNP alleles at multiple loci and skin color variation among races.

  3. Defective copper binding to apo-ceruloplasmin in a rat model and patients with Wilson's disease.

    Science.gov (United States)

    Kojimahara, N; Nakabayashi, H; Shikata, T; Esumi, M

    1995-06-01

    To examine the mechanism of decrease in serum ceruloplasmin (Cp) in Long-Evans Cinnamon (LEC) rats, a proposed model of Wilson's disease, we analyzed Cp products at the stages of transcription and translation. Northern blot analysis and immunoblot analysis showed that the level and the molecular size of Cp mRNA and protein in LEC rats were similar to those in control Long-Evans-Agouti (LEA) rats. However, the ferroxidase activity of Cp was significantly decreased in LEC rats. We separated serum Cp into two forms by native polyacrylamide gel electrophoresis with pH modification: one was a holo-Cp with copper and ferroxidase activity, and the other was an inactive apo-Cp without copper. Holo-Cp was the predominant form in LEA rats and normal humans, whereas apo-Cp was the major form in LEC rats and patients with Wilson's disease. The cosegregation of apo-Cp predominance with the disease in LEC rats was analyzed using backcross rats. Apo-Cp was dominant in 8 of 11 offspring with disease but in none of 19 normal offspring. These results indicate that a genetic disturbance of copper binding to apo-Cp may be closely associated with the pathogenesis in LEC rats, and probably in Wilson's disease.

  4. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease.

    Science.gov (United States)

    Li, Y; Togashi, Y; Sato, S; Emoto, T; Kang, J H; Takeichi, N; Kobayashi, H; Kojima, Y; Une, Y; Uchino, J

    1991-05-01

    Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, resembling the histologic features of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity, and may be dealing with a rat form of Wilson's disease. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism and for developing treatment strategies for Wilson's disease and other abnormal copper metabolism in humans.

  5. How the leopard hides its spots: ASIP mutations and melanism in wild cats.

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    Alexsandra Schneider

    Full Text Available The occurrence of melanism (darkening of the background coloration is documented in 13 felid species, in some cases reaching high frequencies at the population level. Recent analyses have indicated that it arose multiple times in the Felidae, with three different species exhibiting unique mutations associated with this trait. The causative mutations in the remaining species have so far not been identified, precluding a broader assessment of the evolutionary dynamics of melanism in the Felidae. Among these, the leopard (Panthera pardus is a particularly important target for research, given the iconic status of the 'black panther' and the extremely high frequency of melanism observed in some Asian populations. Another felid species from the same region, the Asian golden cat (Pardofelis temminckii, also exhibits frequent records of melanism in some areas. We have sequenced the coding region of the Agouti Signaling Protein (ASIP gene in multiple leopard and Asian golden cat individuals, and identified distinct mutations strongly associated with melanism in each of them. The single nucleotide polymorphism (SNP detected among the P. pardus individuals was caused by a nonsense mutation predicted to completely ablate ASIP function. A different SNP was identified in P. temminckii, causing a predicted amino acid change that should also induce loss of function. Our results reveal two additional cases of species-specific mutations implicated in melanism in the Felidae, and indicate that ASIP mutations may play an important role in naturally-occurring coloration polymorphism.

  6. A central role for C1q/TNF-related protein 13 (CTRP13 in modulating food intake and body weight.

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    Mardi S Byerly

    Full Text Available C1q/TNF-related protein 13 (CTRP13, a hormone secreted by adipose tissue (adipokines, helps regulate glucose metabolism in peripheral tissues. We previously reported that CTRP13 expression is increased in obese and hyperphagic leptin-deficient mice, suggesting that it may modulate food intake and body weight. CTRP13 is also expressed in the brain, although its role in modulating whole-body energy balance remains unknown. Here, we show that CTRP13 is a novel anorexigenic factor in the mouse brain. Quantitative PCR demonstrated that food restriction downregulates Ctrp13 expression in mouse hypothalamus, while high-fat feeding upregulates expression. Central administration of recombinant CTRP13 suppressed food intake and reduced body weight in mice. Further, CTRP13 and the orexigenic neuropeptide agouti-related protein (AgRP reciprocally regulate each other's expression in the hypothalamus: central delivery of CTRP13 suppressed Agrp expression, while delivery of AgRP increased Ctrp13 expression. Food restriction alone reduced Ctrp13 and increased orexigenic neuropeptide gene (Npy and Agrp expression in the hypothalamus; in contrast, when food restriction was coupled to enhanced physical activity in an activity-based anorexia (ABA mouse model, hypothalamic expression of both Ctrp13 and Agrp were upregulated. Taken together, these results suggest that CTRP13 and AgRP form a hypothalamic feedback loop to modulate food intake and that this neural circuit may be disrupted in an anorexic-like condition.

  7. Juvenile-onset loss of lipid-raft domains in attractin-deficient mice

    International Nuclear Information System (INIS)

    Mutations at the attractin (Atrn) locus in mice result in altered pigmentation on an agouti background, higher basal metabolic rate and juvenile-onset hypomyelination leading to neurodegeneration, while studies on human immune cells indicate a chemotaxis regulatory function. The underlying biochemical defect remains elusive. In this report we identify a role for attractin in plasma membrane maintenance. In attractin's absence there is a decline in plasma membrane glycolipid-enriched rafts from normal levels at 8 weeks to a complete absence by 24 weeks. The structural integrity of lipid rafts depends upon cholesterol and sphingomyelin, and can be identified by partitioning within of ganglioside GM1. Despite a significant fall in cellular cholesterol with maturity, and a lesser fall in both membrane and total cellular GM1, these parameters lag behind raft loss, and are normal when hypomyelination/neurodegeneration has already begun thus supporting consequence rather than cause. These findings can be recapitulated in Atrn-deficient cell lines propagated in vitro. Further, signal transduction through complex membrane receptor assemblies is not grossly disturbed despite the complete absence of lipid rafts. We find these results compatible with a role for attractin in plasma membrane maintenance and consistent with the proposal that the juvenile-onset hypomyelination and neurodegeneration represent a defect in attractin-mediated raft-dependent myelin biogenesis

  8. High-fat diet-induced met-hemoglobin formation in rats prone (WOKW) or resistant (DA) to the metabolic syndrome: effect of CoQ10 supplementation.

    Science.gov (United States)

    Orlando, Patrick; Silvestri, Sonia; Brugè, Francesca; Tiano, Luca; Kloting, Ingrid; Falcioni, Giancarlo; Polidori, Carlo

    2014-01-01

    The aim of this study was to evaluate the effects of a high-fat diet (HFD) on oxidative indexes in WistarOttawaKarlsburg W (WOKW) rats used as a model of metabolic syndrome in comparison with Dark Agouti (DA) rats used as a control strain. This syndrome is defined by the occurrence of two or more risk factors including obesity, hypertension, dyslipidemia, and insulin resistance. Forty rats were used in the study and the effect of HFD was evaluated in terms of body weight and both hemoglobin and CoQ oxidative status. Moreover, 16 rats (8 of each strain) were supplemented with 3 mg/100 g b.w. of CoQ10 for 1 month in view of its beneficial properties in cardiovascular disease due to its antioxidant activity in the lipid environment. HFD promoted an increase in body weight, in particular in WOKW males, and in the methemoglobin (met-Hb) index in both strains. Moreover, HFD promoted endogenous CoQ10 oxidation. CoQ10 supplementation was able to efficiently counteract the HFD pro-oxidant effects, preventing met-Hb formation and CoQ oxidation.

  9. Diversity of sandflies (Psychodidae: Phlebotominae) captured in sandstone caves from Central Amazonia, Brazil.

    Science.gov (United States)

    Alves, Veracilda Ribeiro; Freitas, Rui Alves de; Santos, Francisco Lima; Barrett, Toby Vincent

    2011-05-01

    In the present paper we describe the diversity of phlebotomine sandflies collected in three sandstone caves in the municipality of Presidente Figueiredo, state of Amazonas, Brazil. The phlebotomines were captured during 2006 with CDC light traps. Guano samples from inside the Gruta Refúgio do Maruaga were collected to investigate the presence of immature specimens. A total of 2,160 adult phlebotomines representing 15 species were captured. Pintomyia pacae was the dominant species in Gruta dos Animais (1,723 specimens) and Gruta dos Lages (50 specimens) and Deanemyia maruaga new comb (280 specimens) was the dominant species in Gruta Refúgio do Maruaga. A total of 18 guano samples were collected and seven of these samples included immature specimens. A total of 507 immature specimens were captured; 495 of these specimens were larvae and 12 were pupae. The presence of paca (Agouti paca) footprints near Gruta dos Animais and Gruta dos Lages suggests the association of Pi. pacae with this rodent. This finding may explain the abundance of Pi. pacae in these locations, while the species is relatively rare in the forest. Deanemyia maruaga is a cave species that uses guano to breed during its immature stages. Adult specimens of this species are apparently parthenogenetic and autogenous and represent the second record of parthenogenesis for the subfamily Phlebotominae.

  10. Inflammation severely alters thyroid hormone signaling in the central nervous system during experimental allergic encephalomyelitis in rat: Direct impact on OPCs differentiation failure.

    Science.gov (United States)

    Fernández, Mercedes; Baldassarro, Vito A; Sivilia, Sandra; Giardino, Luciana; Calzà, Laura

    2016-09-01

    Differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes is severely impaired by inflammatory cytokines and this could lead to remyelination failure in inflammatory/demyelinating diseases. Due to the role of thyroid hormone in the maturation of OPCs and developmental myelination, in this study we investigated (i) the possible occurrence of dysregulation of thyroid hormone signaling in the CNS tissue during experimental neuroinflammation; (ii) the possible impact of inflammatory cytokines on thyroid hormone signaling and OPCs differentiation in vitro. The disease model is the experimental allergic encephalomyelitis in female Dark-Agouti rats, whereas in vitro experiments were carried out in OPCs derived from neural stem cells. The main results are the following: (i) a strong upregulation of cytokine mRNA expression level was found in the spinal cord during experimental allergic encephalomyelitis; (ii) thyroid hormone signaling in the spinal cord (thyroid hormone receptors; deiodinase; thyroid hormone membrane transporter) is substantially downregulated, due to the upregulation of the thyroid hormone inactivating enzyme deiodinase 3 and the downregulation of thyroid hormone receptors, as investigated at mRNA expression level; (iii) when exposed to inflammatory cytokines, deiodinase 3 is upregulated in OPCs as well, and OPCs differentiation is blocked; (iv) deiodinase 3 inhibition by iopanoic acid recovers OPCs differentiation in the presence on inflammatory cytokines. These data suggest that cellular hypothyroidism occurs during experimental allergic encephalomyelitis, possibly impacting on thyroid hormone-dependent cellular processes, including maturation of OPCs into myelinating oligodendrocytes. GLIA 2016;64:1573-1589. PMID:27404574

  11. Role of hypothalamic melanocortin system in adaptation of food intake to food protein increase in mice.

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    Bruno Pillot

    Full Text Available The hypothalamic melanocortin system--the melanocortin receptor of type 4 (MC4R and its ligands: α-melanin-stimulating hormone (α-MSH, agonist, inducing hypophagia, and agouti-related protein (AgRP, antagonist, inducing hyperphagia--is considered to play a central role in the control of food intake. We tested its implication in the mediation of the hunger-curbing effects of protein-enriched diets (PED in mice. Whereas there was a 20% decrease in food intake in mice fed on the PED, compared to mice fed on an isocaloric starch-enriched diet, there was a paradoxical decrease in expression of the hypothalamic proopiomelanocortin gene, precursor of α-MSH, and increase in expression of the gene encoding AgRP. The hypophagia effect of PED took place in mice with invalidation of either MC4R or POMC, and was even strengthened in mice with ablation of the AgRP-expressing neurons. These data strongly suggest that the hypothalamic melanocortin system does not mediate the hunger-curbing effects induced by changes in the macronutrient composition of food. Rather, the role of this system might be to defend the body against the variations in food intake generated by the nutritional environment.

  12. Genetic Analysis of the Cat Population of North and South of Cali, Colombia

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    Andrés F. PEÑA-CRUZ

    2014-05-01

    Full Text Available The coat genetic markers and skeleton abnormalities have allowed characterize the profile from more than 400 domestic cat populations around the world. 15 years ago, that profile was established in the city of Cali (Colombia. In this study it was determined if north and south of the city are subpopulations and it was compared the total profile against past study. A decrease in allele frequency of a (non-agouti and d (dilution was found, but an increase of five alleles was found, especially in l (long hair and cs (siamese. These differences could be attributed to human selection of more attractive characteristics and gene flow resulting from demographic growth city, which would also explain the first report of inhibitor and ticked abyssinian alleles. Hardy-Weinberg equilibrium was evaluated for the north, south and both areas together, using white spotting and orange loci, determining disequilibrium in orange for the three evaluated areas due to a heterozygotes deficit. North and south were divided into two, each sub-sample showed Hardy-Weinberg equilibrium, although allele frequencies and heterozygosities highlighted microgeographic structure and a relationship between founding time of the neighborhood and heterozygosity. North and south are a single population and aren´t subpopulations (FST= 0,0004, D= 0,0017, as well as nine Colombian populations with which this city was compared. It is suggested to make a microgeographical gene flow analysis and the definition of possible cat colonies in Cali.ANÁLISIS GENÉTICO DE LA POBLACIÓN DE GATOS DEL NORTE Y SUR DE CALI, COLOMBIALos marcadores genéticos del pelaje y malformaciones óseas han permitido caracterizar el perfil genético de más de 400 poblaciones del gato doméstico alrededor del mundo. Unos 15 años atrás se estableció dicho perfil en la ciudad de Cali (Colombia. En este estudio se determinó si el norte y sur de Cali se comportan como subpoblaciones y se comparó el perfil total

  13. Site and strain-specific variation in gut microbiota profiles and metabolism in experimental mice.

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    Melissa K Friswell

    Full Text Available BACKGROUND: The gastrointestinal tract microbiota (GTM of mammals is a complex microbial consortium, the composition and activities of which influences mucosal development, immunity, nutrition and drug metabolism. It remains unclear whether the composition of the dominant GTM is conserved within animals of the same strain and whether stable GTMs are selected for by host-specific factors or dictated by environmental variables. METHODOLOGY/PRINCIPAL FINDINGS: The GTM composition of six highly inbred, genetically distinct strains of mouse (C3H, C57, GFEC, CD1, CBA nu/nu and SCID was profiled using eubacterial -specific PCR-DGGE and quantitative PCR of feces. Animals exhibited strain-specific fecal eubacterial profiles that were highly stable (c. >95% concordance over 26 months for C57. Analyses of mice that had been relocated before and after maturity indicated marked, reproducible changes in fecal consortia and that occurred only in young animals. Implantation of a female BDF1 mouse with genetically distinct (C57 and Agoutie embryos produced highly similar GTM profiles (c. 95% concordance between mother and offspring, regardless of offspring strain, which was also reflected in urinary metabolite profiles. Marked institution-specific GTM profiles were apparent in C3H mice raised in two different research institutions. CONCLUSION/SIGNIFICANCE: Strain-specific data were suggestive of genetic determination of the composition and activities of intestinal symbiotic consortia. However, relocation studies and uterine implantation demonstrated the dominance of environmental influences on the GTM. This was manifested in large variations between isogenic adult mice reared in different research institutions.

  14. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

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    Mayado Andrea

    2011-11-01

    Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

  15. [Some neurological and psychiatric complications of the disorders of the hypothalamo-hypophyseal system].

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    Aszalós, Zsuzsa

    2007-04-22

    Connection between the central nervous system and the endocrine system is extremely complex. The hypothalamus serves as a crucial centre for the integration and coordination of autonomic functions by neuronal and hormonal pathways. It plays a central role in the homeostatic regulation of internal physiological conditions. It controls growth and reproduction, stress reactions, and determines rhythmicity, periodicity and timing of physiological processes. Beside its well-known functions, antidiuretic hormone has a role in social behavior as it enhances aggression via vasopressin receptor 1A. Oxitocin is affected in the formation of maternal behavior, and in other social interactions, like the pair bounding, as well as in analgesia and pain modulation. The corticotrop-releasing hormone acts as a neurotransmitter, it has a special role in stress-behavior, anxiety, and depression, and it blocks deep sleeping. Among the neurotransmitters and neuropeptids of the hypothalamus, serotonin, norepinephrine, GABA, cholecystokinin, neuropeptide-Y, Agouti-related protein, alpha-MSH and ghrelin have essential importance in the eating disorders. The levels of leptin and galanin determine whether formation of anabolic or catabolic neurotransmitters should take place. In the thermoregulation the central thermoreceptors play role, and suprachiasmatic nucleus is responsible for circadian rhythm, through "timing genes". The diseases of the hypothalamus cause most frequently bulimia or anorexia, hypersomnia, impotency, and attacks of anxiety. The most common expansive process of the hypothalamus is craniopharyngioma. The lack or diminution of vasopressin causes diabetes insipidus, while inappropriate antidiuretic hormone secretion induces Schwartz-Barter syndrome. Fröhlich-, Kleine-Levin- or Prader-Willi syndromes have characteristic neuropsychiatric features. The main psychiatric symptom of hypopituitarism is a combination of dementia and delirium. The most characteristic neurological

  16. ROCK1 in AgRP neurons regulates energy expenditure and locomotor activity in male mice.

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    Huang, Hu; Lee, Seung Hwan; Ye, Chianping; Lima, Ines S; Oh, Byung-Chul; Lowell, Bradford B; Zabolotny, Janice M; Kim, Young-Bum

    2013-10-01

    Normal leptin signaling is essential for the maintenance of body weight homeostasis. Proopiomelanocortin- and agouti-related peptide (AgRP)-producing neurons play critical roles in regulating energy metabolism. Our recent work demonstrates that deletion of Rho-kinase 1 (ROCK1) in the AgRP neurons of mice increased body weight and adiposity. Here, we report that selective loss of ROCK1 in AgRP neurons caused a significant decrease in energy expenditure and locomotor activity of mice. These effects were independent of any change in food intake. Furthermore, AgRP neuron-specific ROCK1-deficient mice displayed central leptin resistance, as evidenced by impaired Signal Transducer and Activator of Transcription 3 activation in response to leptin administration. Leptin's ability to hyperpolarize and decrease firing rate of AgRP neurons was also abolished in the absence of ROCK1. Moreover, diet-induced and genetic forms of obesity resulted in reduced ROCK1 activity in murine arcuate nucleus. Of note, high-fat diet also impaired leptin-stimulated ROCK1 activity in arcuate nucleus, suggesting that a defect in hypothalamic ROCK1 activity may contribute to the pathogenesis of central leptin resistance in obesity. Together, these data demonstrate that ROCK1 activation in hypothalamic AgRP neurons is required for the homeostatic regulation of energy expenditure and adiposity. These results further support previous work identifying ROCK1 as a key regulator of energy balance and suggest that targeting ROCK1 in the hypothalamus may lead to development of antiobesity therapeutics. PMID:23885017

  17. Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome

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    Damon T. Jacobs

    2016-07-01

    Full Text Available Primary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139 encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease.

  18. QTL mapping of genes controlling plasma insulin and leptin concentrations: metabolic effect of obesity QTLs identified in an F2 intercross between C57BL/6J and DDD.Cg-A(y) inbred mice.

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    Suto, Jun-ichi

    2013-07-31

    DDD.Cg-A(y) female mice developed massive obesity as compared with B6.Cg-A(y) female mice. We previously identified quantitative trait loci (QTLs) for obesity on chromosomes 1, 6, 9 and 17 in F2 female mice, including F2A(y) (F2 mice with the A(y) allele) and F2 non- A(y) mice (F2 mice without the A(y) allele), produced by crossing C57BL/6J and DDD.Cg-A(y) strains. We here addressed the question whether the obesity QTLs share genetic bases with putative QTLs for plasma glucose, insulin and leptin concentrations. We performed QTL analyses for the first principal component (PC1) extracted from these metabolic measurements to identify the genes that contributed to the comprehensive evaluation of metabolic traits. By single QTL scans, we identified two significant QTLs for insulin concentration on chromosomes 6 and 12, three for leptin concentration on chromosomes 1, 6 and 17, and five for PC1 on chromosomes 1, 6, 12 (two loci) and 17. Although insulin and leptin concentrations and PC1 were not normally distributed in combined F2 mice, results of single QTL scans by parametric and non-parametric methods were very similar. Therefore, QTL scan by the parametric method was performed with the agouti locus genotype as a covariate. A significant QTL × covariate interaction was found for PC1 on chromosome 9. All obesity QTLs had significant metabolic effects. Thus, obesity- and diabetes-related traits in DDD.Cg-A(y) mice were largely controlled by QTLs on chromosomes 1, 6, 9, 12 and 17.

  19. Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-A(y.).

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    Suto, Jun-ichi; Satou, Kunio

    2015-02-01

    The A(y) allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-A(y) male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-A(y) males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-A(y) males. Using a backcross progeny of DDD × (B6 × DDD.Cg-A(y)) F1-A(y), we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-A(y) males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-A(y) and DDD males), individual housing (single DDD.Cg-A(y) male) and single male housing with females (single DDD.Cg-A(y) male with DDD.Cg-A(y) or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-A(y) males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-A(y) males.

  20. Quantitative trait loci that control body weight and obesity in an F2 intercross between C57BL/6J and DDD.Cg-Ay mice.

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    Suto, Jun-ichi

    2011-07-01

    I have developed a congenic mouse strain for the A(y) allele at the agouti locus in an inbred DDD/Sgn strain, DDD.Cg-A(y). DDD.Cg-A(y) females are extremely obese and significantly heavier than B6.Cg-A(y) females. The objectives of this study were to determine the genetic basis of obesity in DDD.Cg-A(y) mice, and to determine whether or not their high body weight was due to the presence of DDD background-specific modifiers. I performed quantitative trait locus (QTL) analyses for body weight and body mass index in two types of F(2) mice [F2 A(y) (F(2) mice carrying the A(y) allele) and F(2) non-A(y) (F2 mice without the A(y) allele)] produced by crossing C57BL/6J females and DDD.Cg-A(y) males. The results of the QTL analysis of F(2) A(y) mice were very similar to those obtained for F(2) non-A(y) mice. It was unlikely that the high body weight of DDD.Cg-A(y) mice was due to the presence of specific modifiers. When both F(2) datasets were merged and analyzed, four significant body weight QTLs were identified on chromosomes 6, 9, and 17 (2 loci) and four significant obesity QTLs were identified on chromosomes 1, 6, 9, and 17. Although the presence of DDD background-specific modifiers was not confirmed, a multifactorial basis of obesity in DDD.Cg-A(y) females was thus revealed.

  1. Quantitative trait loci that control plasma lipid levels in an F2 intercross between C57BL/6J and DDD.Cg-A(y) inbred mouse strains.

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    Suto, Jun-ichi

    2012-04-01

    The objectives of this study were to characterize plasma lipid phenotypes and dissect the genetic basis of plasma lipid levels in an obese DDD.Cg-A(y) mouse strain. Plasma triglyceride (TG) levels were significantly higher in the DDD.Cg-A(y) strain than in the B6.Cg-A(y) strain. In contrast, plasma total-cholesterol (CHO) levels did not substantially differ between the two strains. As a rule, the A(y) allele significantly increased TG levels, but did not increase CHO levels. Quantitative trait locus (QTL) analyses for plasma TG and CHO levels were performed in two types of F(2) female mice [F(2)A(y) (F(2) mice carrying the A(y) allele) and F(2) non- A(y) mice (F(2) mice without the A(y) allele)] produced by crossing C57BL/6J females and DDD.Cg-A(y) males. Single QTL scan identified one significant QTL for TG levels on chromosome 1, and two significant QTLs for CHO levels on chromosomes 1 and 8. When the marker nearest to the QTL on chromosome 1 was used as covariates, four additional significant QTLs for CHO levels were identified on chromosomes 5, 6, and 17 (two loci). In contrast, consideration of the agouti locus genotype as covariates did not detect additional QTLs. DDD.Cg-A(y) showed a low CHO level, although it had Apoa2(b), which was a CHO-increasing allele at the Apoa2 locus. This may have been partly due to the presence of multiple QTLs, which were associated with decreased CHO levels, on chromosome 8.

  2. Investigation of Effect of Nutritional Drink on Chemotherapy-Induced Mucosal Injury and Tumor Growth in an Established Animal Model

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    Eduardo Schiffrin

    2013-09-01

    Full Text Available Chemotherapy-induced mucositis represents a significant burden to quality of life and healthcare costs, and may be improved through enhanced nutritional status. We first determined the safety of two nutritional drinks (plus placebo, and then potential gut protection in tumor-bearing rats in a model of methotrexate-induced mucositis. In study 1, animals were fed one of two test diets (or placebo or control chow pellets for a total of 60 days and were monitored daily. All diets were found to be safe to administer. In study 2, after seven days of receiving diets, a Dark Agouti Mammary Adenocarcinoma (DAMA was transplanted subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular methotrexate administered on two consecutive days; after this time, all animals were given soaked chow. Animals were monitored daily for changes in bodyweight, tumor burden and general health. Animals were killed 10, 12 and 16 days after initially starting diets, and tissues were collected at necropsy. In study 1, animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained 15.1%. In study 2, there was no significant influence of test diet on bodyweight, organ weight, tumor burden or biochemical parameters. Only animals treated with MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non-significant increase in incidence of diarrhea. Administration of these nutritional drinks did not improve symptoms of mucositis.

  3. Investigation of effect of nutritional drink on chemotherapy-induced mucosal injury and tumor growth in an established animal model.

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    Bateman, Emma; Bowen, Joanne; Stringer, Andrea; Mayo, Bronwen; Plews, Erin; Wignall, Anthony; Greenberg, Norman; Schiffrin, Eduardo; Keefe, Dorothy

    2013-09-30

    Chemotherapy-induced mucositis represents a significant burden to quality of life and healthcare costs, and may be improved through enhanced nutritional status. We first determined the safety of two nutritional drinks (plus placebo), and then potential gut protection in tumor-bearing rats in a model of methotrexate-induced mucositis. In study 1, animals were fed one of two test diets (or placebo or control chow pellets) for a total of 60 days and were monitored daily. All diets were found to be safe to administer. In study 2, after seven days of receiving diets, a Dark Agouti Mammary Adenocarcinoma (DAMA) was transplanted subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular methotrexate administered on two consecutive days; after this time, all animals were given soaked chow. Animals were monitored daily for changes in bodyweight, tumor burden and general health. Animals were killed 10, 12 and 16 days after initially starting diets, and tissues were collected at necropsy. In study 1, animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained 15.1%. In study 2, there was no significant influence of test diet on bodyweight, organ weight, tumor burden or biochemical parameters. Only animals treated with MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non-significant increase in incidence of diarrhea. Administration of these nutritional drinks did not improve symptoms of mucositis.

  4. Maternal and postweaning folic acid supplementation interact to influence body weight, insulin resistance, and food intake regulatory gene expression in rat offspring in a sex-specific manner.

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    Huot, Pedro S P; Ly, Anna; Szeto, Ignatius M Y; Reza-López, Sandra A; Cho, Daniel; Kim, Young-In; Anderson, G Harvey

    2016-04-01

    Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic acid content of maternal diets would alter the offspring's metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring's diet with that of the maternal diet. Female Sprague-Dawley rats were placed on a control or a 2.5× folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5× folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid-supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5× the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation.

  5. The connection of monocytes and reactive oxygen species in pain.

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    Dagmar Hackel

    Full Text Available The interplay of specific leukocyte subpopulations, resident cells and proalgesic mediators results in pain in inflammation. Proalgesic mediators like reactive oxygen species (ROS and downstream products elicit pain by stimulation of transient receptor potential (TRP channels. The contribution of leukocyte subpopulations however is less clear. Local injection of neutrophilic chemokines elicits neutrophil recruitment but no hyperalgesia in rats. In meta-analyses the monocytic chemoattractant, CCL2 (monocyte chemoattractant protein-1; MCP-1, was identified as an important factor in the pathophysiology of human and animal pain. In this study, intraplantar injection of CCL2 elicited thermal and mechanical pain in Wistar but not in Dark Agouti (DA rats, which lack p47(phox, a part of the NADPH oxidase complex. Inflammatory hyperalgesia after complete Freund's adjuvant (CFA as well as capsaicin-induced hyperalgesia and capsaicin-induced current flow in dorsal root ganglion neurons in DA were comparable to Wistar rats. Macrophages from DA expressed lower levels of CCR2 and thereby migrated less towards CCL2 and formed limited amounts of ROS in vitro and 4-hydroxynonenal (4-HNE in the tissue in response to CCL2 compared to Wistar rats. Local adoptive transfer of peritoneal macrophages from Wistar but not from DA rats reconstituted CCL2-triggered hyperalgesia in leukocyte-depleted DA and Wistar rats. A pharmacological stimulator of ROS production (phytol restored CCL2-induced hyperalgesia in vivo in DA rats. In Wistar rats, CCL2-induced hyperalgesia was completely blocked by superoxide dismutase (SOD, catalase or tempol. Likewise, inhibition of NADPH oxidase by apocynin reduced CCL2-elicited hyperalgesia but not CFA-induced inflammatory hyperalgesia. In summary, we provide a link between CCL2, CCR2 expression on macrophages, NADPH oxidase, ROS and the development CCL2-triggered hyperalgesia, which is different from CFA-induced hyperalgesia. The study

  6. Genetic factors control nicotine self-administration in isogenic adolescent rat strains.

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    Hao Chen

    Full Text Available Adult cigarette smokers usually become dependent on cigarettes during adolescence. Despite recent advances in addiction genetics, little data delineates the genetic factors that account for the vulnerability of humans to smoke tobacco. We studied the operant nicotine self-administration (SA behavior of six inbred strains of adolescent male rats (Fisher 344, Brown Norway, Dark Agouti, Spontaneous Hypertensive Rat, Wistar Kyoto and Lewis and six selected F1 hybrids. All rats were trained to press a lever to obtain food starting on postnatal day (PN 32, and then nicotine (0.03 mg/kg/infusion, i.v. reinforcement was made available on PN41-42 (10 consecutive daily 2 h sessions. Of the 12 isogenic strains, Fisher rats self-administered the fewest nicotine infusions (1.45 ± 0.36/d during the last 3 d, while Lewis rats took the most nicotine (13.0 ± 1.4/d. These strains sorted into high, intermediate and low self-administration groups in 2, 2, and 8 strains, respectively. The influence of heredity on nicotine SA (0.64 is similar to that reported for humans. Therefore, this panel of isogenic rat strains effectively models the overall impact of genetics on the vulnerability to acquire nicotine-reinforced behavior during adolescence. Separate groups of rats responded for food starting on PN41. The correlation between nicotine and food reward was not significant. Hence, the genetic control of the motivation to obtain nicotine is distinctly different from food reward, indicating the specificity of the underlying genetic mechanisms. Lastly, the behavior of F1 hybrids was not predicted from the additive behavior of the parental strains, indicating the impact of significant gene-gene interactions on the susceptibility to nicotine reward. Taken together, the behavioral characteristics of this model indicate its strong potential to identify specific genes mediating the human vulnerability to smoke cigarettes.

  7. Neural and hormonal control of food hoarding.

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    Bartness, Timothy J; Keen-Rhinehart, E; Dailey, M J; Teubner, B J

    2011-09-01

    Many animals hoard food, including humans, but despite its pervasiveness, little is known about the physiological mechanisms underlying this appetitive behavior. We summarize studies of food hoarding in humans and rodents with an emphasis on mechanistic laboratory studies of species where this behavior importantly impacts their energy balance (hamsters), but include laboratory rat studies although their wild counterparts do not hoard food. The photoperiod and cold can affect food hoarding, but food availability is the most significant environmental factor affecting food hoarding. Food-deprived/restricted hamsters and humans exhibit large increases in food hoarding compared with their fed counterparts, both doing so without overeating. Some of the peripheral and central peptides involved in food intake also affect food hoarding, although many have not been tested. Ad libitum-fed hamsters given systemic injections of ghrelin, the peripheral orexigenic hormone that increases with fasting, mimics food deprivation-induced increases in food hoarding. Neuropeptide Y or agouti-related protein, brain peptides stimulated by ghrelin, given centrally to ad libitum-fed hamsters, duplicates the early and prolonged postfood deprivation increases in food hoarding, whereas central melanocortin receptor agonism tends to inhibit food deprivation and ghrelin stimulation of hoarding. Central or peripheral leptin injection or peripheral cholecystokinin-33, known satiety peptides, inhibit food hoarding. Food hoarding markedly increases with pregnancy and lactation. Because fasted and/or obese humans hoard more food in general, and more high-density/high-fat foods specifically, than nonfasted and/or nonobese humans, understanding the mechanisms underlying food hoarding could provide another target for behavioral/pharmacological approaches to curb obesity.

  8. Enhanced susceptibility of ovaries from obese mice to 7,12-dimethylbenz[a]anthracene-induced DNA damage

    International Nuclear Information System (INIS)

    7,12-Dimethylbenz[a]anthracene (DMBA) depletes ovarian follicles and induces DNA damage in extra-ovarian tissues, thus, we investigated ovarian DMBA-induced DNA damage. Additionally, since obesity is associated with increased offspring birth defect incidence, we hypothesized that a DMBA-induced DNA damage response (DDR) is compromised in ovaries from obese females. Wild type (lean) non agouti (a/a) and KK.Cg-Ay/J heterozygote (obese) mice were dosed with sesame oil or DMBA (1 mg/kg; intraperitoneal injection) at 18 weeks of age, for 14 days. Total ovarian RNA and protein were isolated and abundance of Ataxia telangiectasia mutated (Atm), X-ray repair complementing defective repair in Chinese hamster cells 6 (Xrcc6), breast cancer type 1 (Brca1), Rad 51 homolog (Rad51), poly [ADP-ribose] polymerase 1 (Parp1) and protein kinase, DNA-activated, catalytic polypeptide (Prkdc) were quantified by RT-PCR or Western blot. Phosphorylated histone H2AX (γH2AX) level was determined by Western blotting. Obesity decreased (P < 0.05) basal protein abundance of PRKDC and BRCA1 proteins but increased (P < 0.05) γH2AX and PARP1 proteins. Ovarian ATM, XRCC6, PRKDC, RAD51 and PARP1 proteins were increased (P < 0.05) by DMBA exposure in lean mice. A blunted DMBA-induced increase (P < 0.05) in XRCC6, PRKDC, RAD51 and BRCA1 was observed in ovaries from obese mice, relative to lean counterparts. Taken together, DMBA exposure induced γH2AX as well as the ovarian DDR, supporting that DMBA causes ovarian DNA damage. Additionally, ovarian DDR was partially attenuated in obese females raising concern that obesity may be an additive factor during chemical-induced ovotoxicity. - Highlights: • DMBA induces markers of ovarian DNA damage. • Obesity induces low level ovarian DNA damage. • DMBA-induced DNA repair response is altered by obesity

  9. Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

    Science.gov (United States)

    Alvarez-Crespo, Mayte; Csikasz, Robert I.; Martínez-Sánchez, Noelia; Diéguez, Carlos; Cannon, Barbara; Nedergaard, Jan; López, Miguel

    2016-01-01

    Objective Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Methods Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT). Conclusions We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. PMID:27069867

  10. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier integrity through a mechanism involving P2X7 receptors.

    Science.gov (United States)

    Rubio-Araiz, Ana; Perez-Hernandez, Mercedes; Urrutia, Andrés; Porcu, Francesca; Borcel, Erika; Gutierrez-Lopez, Maria Dolores; O'Shea, Esther; Colado, Maria Isabel

    2014-08-01

    The recreational drug 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') produces a neuro-inflammatory response in rats characterized by an increase in microglial activation and IL-1β levels. The integrity of the blood-brain barrier (BBB) is important in preserving the homeostasis of the brain and has been shown to be affected by neuro-inflammatory processes. We aimed to study the effect of a single dose of MDMA on the activity of metalloproteinases (MMPs), expression of extracellular matrix proteins, BBB leakage and the role of the ionotropic purinergic receptor P2X7 (P2X7R) in the changes induced by the drug. Adult male Dark Agouti rats were treated with MDMA (10 mg/kg, i.p.) and killed at several time-points in order to evaluate MMP-9 and MMP-3 activity in the hippocampus and laminin and collagen-IV expression and IgG extravasation in the dentate gyrus. Microglial activation, P2X7R expression and localization were also determined in the dentate gyrus. Separate groups were treated with MDMA and the P2X7R antagonists Brilliant Blue G (BBG; 50 mg/kg, i.p.) or A-438079 (30 mg/kg, i.p.). MDMA increased MMP-3 and MMP-9 activity, reduced laminin and collagen-IV expression and increased IgG immunoreactivity. In addition, MDMA increased microglial activation and P2X7R immunoreactivity in these cells. BBG suppressed the increase in MMP-9 and MMP-3 activity, prevented basal lamina degradation and IgG extravasation into the brain parenchyma. A-438079 also prevented the MDMA-induced reduction in laminin and collagen-IV immunoreactivity. These results indicate that MDMA alters BBB permeability through an early P2X7R-mediated event, which in turn leads to enhancement of MMP-9 and MMP-3 activity and degradation of extracellular matrix.

  11. A study on the mechanisms by which minocycline protects against MDMA ('ecstasy')-induced neurotoxicity of 5-HT cortical neurons.

    Science.gov (United States)

    Orio, Laura; Llopis, Noemi; Torres, Elisa; Izco, Maria; O'Shea, Esther; Colado, M Isabel

    2010-08-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a selective 5-HT neurotoxin in rat brain which has been shown to produce acute neuroinflammation characterized by activation of microglia and release of interleukin-1beta (IL-1beta). We aimed to determine whether or not minocycline, a semi-synthetic tetracycline antibiotic capable of inhibiting microglial activation, could prevent the inflammatory response and reduce the toxicity induced by MDMA. Adult male Dark Agouti rats were given minocycline twice a day for 2 days (45 mg/kg on the first day and 90 mg/kg on the second day; 12-h apart, i.p.). MDMA (12.5 mg/kg; i.p.) was given after the third minocycline injection and animals were killed either 1 h later for the determination of NFkappaB binding activity, 3 h later for the determination of IL-1beta, 24 h later for the determination of microglial activation or 7 days later for the determination of [(3)H]-paroxetine binding as a measure of 5-HT neurotoxicity. MDMA increased NFkappaB activation, IL-1beta release and microglial activation both in the frontal cortex and in the hypothalamus and 7 days later produced a reduction in the density of 5-HT uptake sites in both these brain areas. Minocycline prevented the MDMA-induced increase in NFkappaB activation, IL-1beta release and microglial activation in the frontal cortex and prevented the 5-HT neurotoxicity 7 days later. However, in the hypothalamus, in spite of preventing MDMA-induced microglial activation, minocycline failed to prevent MDMA-induced NFkappaB activation, IL-1beta release and neurotoxicity. This suggests that the protective mechanism of minocycline against MDMA-induced neurotoxicity in frontal cortex involves inhibition of MDMA-induced NFkappaB activation possibly through a reduction in IL-1beta signalling. PMID:19777321

  12. CARACTERIZACIÓN BROMATOLÓGICA Y MICROBIOLÓGICA DE CARNES PROCEDENTES DE ESPECIES DE ANIMALES REGIONALES DE LA AMAZONIA PERUANA PARA CONSUMO HUMANO

    Directory of Open Access Journals (Sweden)

    Ronald M. Lozano

    2012-12-01

    Full Text Available La investigación consistió en la caracterización bromatológica y determinación microbiológica de muestras de carnes procedentes de ocho especies de animales silvestres: huangana (Tayassu pecari, majaz o picuro (Agouti paca, sajino (Tayassu tajacu, venado colorado (Mazama americana, tapir (Tapirus terrestris, añuje (Dasyprota fuliginosa, ronsoco (Hydrochaeris hydrochaeris y armadillo (Dasypus novemcinctus; en las localidades de Puerto Belén-Roya-Utucuro, Santa Rosa de Aguaytía, Santa Luz de Abujao, Tacshitea–Sector Parinari en dos ocasiones, ubicadas en las márgenes del río Ucayali y sus afluentes, que fueron analizarlas por la empresa Servicios de Asesoramiento Técnico S.A.C. en Lima.  La caracterización bromatológica indicó que el añuje (Dasyprota fuliginosa mostró el mayor contenido en Proteína cruda seguido de la huangana (Tayassu pecari; en el contenido de grasa destacaron las especies  armadillo (Dasypus novemcinctus y la sachavaca (Tapirus terrestris así también en su contenido calórico.  La especie venado colorado (Mazama americana mostró un mayor valor en cenizas y en carbohidratos la especie huangana (Tayassu pecari.  La determinación microbiológica indicó que todas las muestras presentaron niveles de contaminación dentro de los límites permitidos para aerobios mesófilos viables y niveles de contaminación por coliformes totales, coliformes fecales, algunos muy elevados y también de mohos y levaduras.  Todos presentaron ausencia de Salmonella.

  13. Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 tesla Clinical whole-body system after intraperitoneal contrast injection

    Energy Technology Data Exchange (ETDEWEB)

    Heckl, S.; Naegele, T.; Klose, U. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Herrmann, M.; Gaertner, S.; Weissert, R. [Dept. of Neurology, Medical School, Univ. of Tuebingen (Germany); Schick, F. [Dept. of Radiology, Medical School, Univ. of Tuebingen (Germany); Kueker, W. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Dept. of Neuroradiology, Radcliffe Infirmary, Oxford, England (United Kingdom)

    2004-11-01

    Purpose: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) wholebody MR system. Materials and Methods: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weighted images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. Results: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense area in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. Conclusions: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats. (orig.)

  14. Peptides and Food Intake

    Directory of Open Access Journals (Sweden)

    Carmen Sobrino Crespo

    2014-04-01

    Full Text Available Nutrients created by the digestion of food are proposed to active G protein coupled receptors on the luminal side of enteroendocrine cells e.g. the L-cell. This stimulates the release of gut hormones. Hormones released from the gut and adipose tissue play an important rol in the regulation of food intake and energy expenditure (1.Many circulating signals, including gut hormones, can influence the activity of the arcuate nucleus (ARC neurons directly, after passing across the median eminence. The ARC is adjacent to the median eminence, a circumventricular organ with fenestrated capillaries and hence an incomplete blood-brain barrier (2. The ARC of the hypothalamus is believed to play a crucial role in the regulation of food intake and energy homeostasis. The ARC contains two populations of neurons with opposing effect on food intake (3. Medially located orexigenic neurons (i.e those stimulating appetite express neuropeptide Y (NPY and agouti-related protein (AgRP (4-5. Anorexigenic neurons (i.e. those inhibiting appetite in the lateral ARC express alpha-melanocyte stimulating hormone (α-MSH derived from pro-opiomelanocortin (POMC and cocaine and amphetamine-regulated transcript (CART (6. The balance between activities of these neuronal circuits is critical to body weight regulation.In contrast, other peripheral signals influence the hypothalamus indirectly via afferent neuronal pathway and brainstem circuits. In this context gastrointestinal’s vagal afferents are activated by mechanoreceptors and chemoreceptors, and converge in the nucleus of the tractus solitaries (NTS of the brainstem. Neuronal projections from the NTS, in turn, carry signals to the hypotalamus (1, 7. Gut hormones also alter the activity of the ascending vagal pathway from the gut to the brainstem. In the cases of ghrelin and Peptide tyrosine tyrosine (PYY, there are evidences for both to have a direct action on the arcuate nucleus and an action via the vagus nerve a

  15. Enhanced susceptibility of ovaries from obese mice to 7,12-dimethylbenz[a]anthracene-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2014-12-01

    7,12-Dimethylbenz[a]anthracene (DMBA) depletes ovarian follicles and induces DNA damage in extra-ovarian tissues, thus, we investigated ovarian DMBA-induced DNA damage. Additionally, since obesity is associated with increased offspring birth defect incidence, we hypothesized that a DMBA-induced DNA damage response (DDR) is compromised in ovaries from obese females. Wild type (lean) non agouti (a/a) and KK.Cg-Ay/J heterozygote (obese) mice were dosed with sesame oil or DMBA (1 mg/kg; intraperitoneal injection) at 18 weeks of age, for 14 days. Total ovarian RNA and protein were isolated and abundance of Ataxia telangiectasia mutated (Atm), X-ray repair complementing defective repair in Chinese hamster cells 6 (Xrcc6), breast cancer type 1 (Brca1), Rad 51 homolog (Rad51), poly [ADP-ribose] polymerase 1 (Parp1) and protein kinase, DNA-activated, catalytic polypeptide (Prkdc) were quantified by RT-PCR or Western blot. Phosphorylated histone H2AX (γH2AX) level was determined by Western blotting. Obesity decreased (P < 0.05) basal protein abundance of PRKDC and BRCA1 proteins but increased (P < 0.05) γH2AX and PARP1 proteins. Ovarian ATM, XRCC6, PRKDC, RAD51 and PARP1 proteins were increased (P < 0.05) by DMBA exposure in lean mice. A blunted DMBA-induced increase (P < 0.05) in XRCC6, PRKDC, RAD51 and BRCA1 was observed in ovaries from obese mice, relative to lean counterparts. Taken together, DMBA exposure induced γH2AX as well as the ovarian DDR, supporting that DMBA causes ovarian DNA damage. Additionally, ovarian DDR was partially attenuated in obese females raising concern that obesity may be an additive factor during chemical-induced ovotoxicity. - Highlights: • DMBA induces markers of ovarian DNA damage. • Obesity induces low level ovarian DNA damage. • DMBA-induced DNA repair response is altered by obesity.

  16. Discovery of Gene Sources for Economic Traits in Hanwoo by Whole-genome Resequencing

    Science.gov (United States)

    Shin, Younhee; Jung, Ho-jin; Jung, Myunghee; Yoo, Seungil; Subramaniyam, Sathiyamoorthy; Markkandan, Kesavan; Kang, Jun-Mo; Rai, Rajani; Park, Junhyung; Kim, Jong-Joo

    2016-01-01

    Hanwoo, a Korean native cattle (Bos taurus coreana), has great economic value due to high meat quality. Also, the breed has genetic variations that are associated with production traits such as health, disease resistance, reproduction, growth as well as carcass quality. In this study, next generation sequencing technologies and the availability of an appropriate reference genome were applied to discover a large amount of single nucleotide polymorphisms (SNPs) in ten Hanwoo bulls. Analysis of whole-genome resequencing generated a total of 26.5 Gb data, of which 594,716,859 and 592,990,750 reads covered 98.73% and 93.79% of the bovine reference genomes of UMD 3.1 and Btau 4.6.1, respectively. In total, 2,473,884 and 2,402,997 putative SNPs were discovered, of which 1,095,922 (44.3%) and 982,674 (40.9%) novel SNPs were discovered against UMD3.1 and Btau 4.6.1, respectively. Among the SNPs, the 46,301 (UMD 3.1) and 28,613 SNPs (Btau 4.6.1) that were identified as Hanwoo-specific SNPs were included in the functional genes that may be involved in the mechanisms of milk production, tenderness, juiciness, marbling of Hanwoo beef and yellow hair. Most of the Hanwoo-specific SNPs were identified in the promoter region, suggesting that the SNPs influence differential expression of the regulated genes relative to the relevant traits. In particular, the non-synonymous (ns) SNPs found in CORIN, which is a negative regulator of Agouti, might be a causal variant to determine yellow hair of Hanwoo. Our results will provide abundant genetic sources of variation to characterize Hanwoo genetics and for subsequent breeding. PMID:26954201

  17. Cloning, characterization and targeting of the mouse HEXA gene

    Energy Technology Data Exchange (ETDEWEB)

    Wakamatsu, N.; Trasler, J.M.; Gravel, R.A. [McGill Univ., Quebec (Canada)] [and others

    1994-09-01

    The HEXA gene, encoding the {alpha} subunit of {beta}-hexosaminidase A, is essential for the metabolism of ganglioside G{sub M2}, and defects in this gene cause Tay-Sachs disease in humans. To elucidate the role of the gene in the nervous system of the mouse and to establish a mouse model of Tay-Sachs disease, we have cloned and characterized the HEXA gene and targeted a disruption of the gene in mouse ES cells. The mouse HEXA gene spans {approximately}26 kb and consists of 14 exons, similar to the human gene. A heterogeneous transcription initiation site was identified 21-42 bp 5{prime} of the initiator ATG, with two of the sites fitting the consensus CTCA (A = start) as seen for some weak initiator systems. Promoter analysis showed that the first 150 bp 5{prime} of the ATG contained 85% of promoter activity observed in constructs containing up to 1050 bp of 5{prime} sequence. The active region contained a sequence matching that of the adenovirus major late promoter upstream element factor. A survey of mouse tissues showed that the highest mRNA levels were in (max to min): testis (5.5 x brain cortex), adrenal, epididymis, heart, brain, lung, kidney, and liver (0.3 x brain cortex). A 12 kb BstI/SalI fragment containing nine exons was disrupted with the insertion of the bacterial neo{sup r} gene in exon 11 and was targeted into 129/Sv ES cells by homologous recombination. Nine of 153 G418 resistant clones were correctly targeted as confirmed by Southern blotting. The heterozygous ES cells were microinjected into mouse blastocysts and implanted into pseudo-pregnant mice. Nine male chimeric mice, showing that 40-95% chimerism for the 129/Sv agouti coat color marker, are being bred in an effort to generate germline transmission of the disrupted HEXA gene.

  18. A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq.

    Directory of Open Access Journals (Sweden)

    Tianyuan Wang

    Full Text Available Repetitive elements (REs comprise 40-60% of the mammalian genome and have been shown to epigenetically influence the expression of genes through the formation of fusion transcript (FTs. We previously showed that an intracisternal A particle forms an FT with the agouti gene in mice, causing obesity/type 2 diabetes. To determine the frequency of FTs genome-wide, we developed a TopHat-Fusion-based analytical pipeline to identify FTs with high specificity. We applied it to an RNA-seq dataset from the nucleus accumbens (NAc of mice repeatedly exposed to cocaine. Cocaine was previously shown to increase the expression of certain REs in this brain region. Using this pipeline that can be applied to single- or paired-end reads, we identified 438 genes expressing 813 different FTs in the NAc. Although all types of studied repeats were present in FTs, simple sequence repeats were underrepresented. Most importantly, reverse-transcription and quantitative PCR validated the expression of selected FTs in an independent cohort of animals, which also revealed that some FTs are the prominent isoforms expressed in the NAc by some genes. In other RNA-seq datasets, developmental expression as well as tissue specificity of some FTs differed from their corresponding non-fusion counterparts. Finally, in silico analysis predicted changes in the structure of proteins encoded by some FTs, potentially resulting in gain or loss of function. Collectively, these results indicate the robustness of our pipeline in detecting these new isoforms of genes, which we believe provides a valuable tool to aid in better understanding the broad role of REs in mammalian cellular biology.

  19. [STUDY RELATIVE EXPRESSION OF GENES THAT CONTROL GLUCOSE METABOLISM IN THE LIVER IN MICE WITH DEVELOPMENT OF MELANOCORTIN OBESITY].

    Science.gov (United States)

    Baklanov, A V; Bazhan, N M

    2015-06-01

    The relative gene expressions of glucose-6-phosphatase (G6P), phosphoenolpyruvate carbo- xykinase (PEPCK)--markers of gluconeogenesis, glucokinase (GK)--a marker of glycolysis, glucose transporter type 2 (GLUT2)--a marker of input and output of glucose in the liver were measured during the development of melanocortin (MC) obesity in male mice of C57BL/6J strain with mutation yellow in the Agouti locus (Ay/a mice). The mutation decreases MC receptor activity and induces hyperphagia and MC obesity. The males of the same line with mutation nonagouti were used as control. Tissue samples were taken at age 10 (before obesity), 15 (moderate obesity) and 30 (developed obesity) weeks. It has been shown that Ay/a mice had decreased glucose tolerance since 10-week age. There were age-related changes in mRNA levels in the liver of Ay/a mice, unlike a/a mice. In Ay/a mice the mRNA GLUT2 levels at the age of 10 weeks, mRNA GK levels at the age of 15 weeks, and mRNA G6P levels at the age of 3O weeks were higher than those in Ada mice of other ages. InAYfa mice the mRNA GK levels at the age of 15 weeks and mRNA G6F levels at the age of 30 weeks were increased relatively to those in a/a mice. Thus, Ay/a mice before the development of MK obesity had changes in the mRNA levels genes of proteins that regulate hepatic glucose metabolism, which may contribute to the compensation of glucose metabolism disorders caused by a hereditary decrease of MK system activity

  20. Development of a novel pink-eyed dilution mouse model showing progressive darkening of the eyes and coat hair with aging.

    Science.gov (United States)

    Ishikawa, Akira; Sugiyama, Makoto; Hondo, Eiichi; Kinoshita, Keiji; Yamagishi, Yuki

    2015-01-01

    Oca2(p-cas) (oculocutaneous albinism II; pink-eyed dilution castaneus) is a coat color mutant gene on mouse chromosome 7 that arose spontaneously in wild Mus musculus castaneus mice. Mice homozygous for Oca2(p-cas) usually exhibit pink eyes and gray coat hair on the non-agouti genetic background, and this ordinary phenotype remains unchanged throughout life. During breeding of a mixed strain carrying this gene on the C57BL/6J background, we discovered a novel spontaneous mutation that causes darkening of the eyes and coat hair with aging. In this study, we developed a novel mouse model showing this unique phenotype. Gross observations revealed that the pink eyes and gray coat hair of the novel mutant young mice became progressively darker in color by approximately 3 months after birth. Light and transmission-electron microscopic observations revealed a marked increase in melanin pigmentation of coat hair shafts and choroid of the eye in the novel mice compared to that in the ordinary mice. Sequence analysis of Oca2(p-cas) revealed a 4.1-kb deletion involving exons 15 and 16 of its wild-type gene. However, there was no sequence difference between the two types of mutant mice. Mating experiments suggested that the novel mutant phenotype was not inherited in a simple fashion, due to incomplete penetrance. The novel spontaneous mutant mouse is the first example of progressive hair darkening animals and is an essential animal model for understanding of the regulation mechanisms of melanin biosynthesis with aging. PMID:25739360

  1. Review of Research Progress on the Related Genes with the Coat Color of Alpaca%羊驼毛色相关基因研究进展的综述

    Institute of Scientific and Technical Information of China (English)

    邸文达; 杨川

    2012-01-01

    羊驼毛纤维颜色丰富,具有22种天然色,与其他哺乳动物一样,主要由遗传基因决定。掌握控制羊驼毛色基因的改变,可以有效地控制羊驼毛色的转变。哺乳动物的毛色表型与动物体内黑色素的种类、数量、合成及分布有关。在羊驼皮肤组织中,Agouti基因、MC1R基因、酪氨酸酶基因家族、KIT基因、AIF基因、β-catenin基因、Wnt3α基因、Mitf-M基因、EDNRA基因、EDNRB基因、CDK5基因、PRS5基因、P基因及花斑突变都参与羊驼毛色的形成与调控。综述了羊驼毛色相关基因的研究进展。%The hair fiber color of alpaca,with 22 natural colors, is mainly determined by heredity gene like other mammals . To master and control the changes the hair color genes of alpaca could effectively regulate the changes of hair colors of alpaca. The hair phenotypes of mammals are related to the types, amount,composition and distribution of melanin in animals. In the skin tissue of alpaca, Agouti gene ,MC1R gene, tyrosine gene family, KIT gene ,A1F gene ,~-catenin gene, Wnt3et gene ,Mitf-M gene ,EDNRA gene ,EDNRB gene, CDK5 gene, PRS5 gene, P gene and piebaldness mutation all participated in the formation and regulation of alpaca hair color.

  2. Blockage of the Neonatal Leptin Surge Affects the Gene Expression of Growth Factors, Glial Proteins, and Neuropeptides Involved in the Control of Metabolism and Reproduction in Peripubertal Male and Female Rats.

    Science.gov (United States)

    Mela, Virginia; Díaz, Francisca; Lopez-Rodriguez, Ana Belen; Vázquez, María Jesús; Gertler, Arieh; Argente, Jesús; Tena-Sempere, Manuel; Viveros, María-Paz; Chowen, Julie A

    2015-07-01

    Leptin (Lep) is important in the development of neuroendocrine circuits involved in metabolic control. Because both Lep and metabolism influence pubertal development, we hypothesized that early changes in Lep signaling could also modulate hypothalamic (HT) systems involved in reproduction. We previously demonstrated that a single injection of a Lep antagonist (Antag) on postnatal day (PND)9, coincident with the neonatal Lep peak, induced sexually dimorphic modifications in trophic factors and markers of cell turnover and neuronal maturation in the HT on PND13. Here, our aim was to investigate whether the alterations induced by Lep antagonism persist into puberty. Accordingly, male and female rats were treated with a pegylated super Lep Antag from PND5 to PND9 and killed just before the normal appearance of external signs of puberty (PND33 in females and PND43 in males). There was no effect on body weight, but in males food intake increased, subcutaneous adipose tissue decreased and HT neuropeptide Y and Agouti-related peptide mRNA levels were reduced, with no effect in females. In both sexes, the Antag increased HT mRNA levels of the kisspeptin receptor, G protein-coupled recepter 54 (Gpr54). Expression of the Lep receptor, trophic factors, and glial markers were differently affected in the HT of peripubertal males and females. Lep production in adipose tissue was decreased in Antag-treated rats of both sexes, with production of other cytokines being differentially regulated between sexes. In conclusion, in addition to the long-term effects on metabolism, changes in neonatal Lep levels modifies factors involved in reproduction that could possibly affect sexual maturation.

  3. Pioglitazone administration alters ovarian gene expression in aging obese lethal yellow mice

    Directory of Open Access Journals (Sweden)

    Weber Mitch

    2008-03-01

    Full Text Available Abstract Background Women with polycystic ovary syndrome (PCOS are often treated with insulin-sensitizing agents, e.g. thiazolidinediones (TZD, which have been shown to reduce androgen levels and improved ovulatory function. Acting via peroxisome proliferator-activated receptor (PPAR gamma, TZD alter the expression of a large variety of genes. Lethal yellow (LY; C57BL/6J Ay/a mice, possessing a mutation (Ay in the agouti gene locus, exhibit progressive obesity, reproductive dysfunction, and altered metabolic regulation similar to women with PCOS. The current study was designed to test the hypothesis that prolonged treatment of aging LY mice with the TZD, pioglitazone, alters the ovarian expression of genes that may impact reproduction. Methods Female LY mice received daily oral doses of either 0.01 mg pioglitazone (n = 4 or an equal volume of vehicle (DMSO; n = 4 for 8 weeks. At the end of treatment, ovaries were removed and DNA microarrays were used to analyze differential gene expression. Results Twenty-seven genes showed at least a two-fold difference in ovarian expression with pioglitazone treatment. These included leptin, angiopoietin, angiopoietin-like 4, Foxa3, PGE1 receptor, resistin-like molecule-alpha (RELM, and actin-related protein 6 homolog (ARP6. For most altered genes, pioglitazone changed levels of expression to those seen in untreated C57BL/6J(a/a non-mutant lean mice. Conclusion TZD administration may influence ovarian function via numerous diverse mechanisms that may or may not be directly related to insulin/IGF signaling.

  4. Seasonal Differences in Relative Gene Expression of Putative Central Appetite Regulators in Arctic Charr (Salvelinus alpinus Do Not Reflect Its Annual Feeding Cycle.

    Directory of Open Access Journals (Sweden)

    Anja Striberny

    Full Text Available The highly seasonal anadromous Arctic charr (Salvelinus alpinus was used to investigate the possible involvement of altered gene expression of brain neuropeptides in seasonal appetite regulation. Pro-opiomelanocortin (POMCA1, POMCA2, Cocaine and amphetamine regulated transcript (CART, Agouti related Peptide (AgRP, Neuropeptide Y (NPY and Melanocortin Receptor 4 (MC4-R genes were examined. The function of centrally expressed Leptin (Lep in fish remains unclear, so Lep (LepA1, LepA2 and Leptin Receptor (LepR genes were included in the investigation. In a ten months study gene expression was analysed in hypothalamus, mesencephalon and telencephalon of immature charr held under natural photoperiod (69°38'N and ambient temperature and given excess feed. From April to the beginning of June the charr did not feed and lost weight, during July and August they were feeding and had a marked increase in weight and condition factor, and from November until the end of the study the charr lost appetite and decreased in weight and condition factor. Brain compartments were sampled from non-feeding charr (May, feeding charr (July, and non-feeding charr (January. Reverse transcription real-time quantitative PCR revealed temporal patterns of gene expression that differed across brain compartments. The non-feeding charr (May, January had a lower expression of the anorexigenic LepA1, MC4-R and LepR in hypothalamus and a higher expression of the orexigenic NPY and AgRP in mesencephalon, than the feeding charr (July. In the telencephalon, LepR was more highly expressed in January and May than in July. These results do not indicate that changes in central gene expression of the neuropeptides investigated here directly induce seasonal changes in feeding in Arctic charr.

  5. A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq.

    Science.gov (United States)

    Wang, Tianyuan; Santos, Janine H; Feng, Jian; Fargo, David C; Shen, Li; Riadi, Gonzalo; Keeley, Elizabeth; Rosh, Zachary S; Nestler, Eric J; Woychik, Richard P

    2016-01-01

    Repetitive elements (REs) comprise 40-60% of the mammalian genome and have been shown to epigenetically influence the expression of genes through the formation of fusion transcript (FTs). We previously showed that an intracisternal A particle forms an FT with the agouti gene in mice, causing obesity/type 2 diabetes. To determine the frequency of FTs genome-wide, we developed a TopHat-Fusion-based analytical pipeline to identify FTs with high specificity. We applied it to an RNA-seq dataset from the nucleus accumbens (NAc) of mice repeatedly exposed to cocaine. Cocaine was previously shown to increase the expression of certain REs in this brain region. Using this pipeline that can be applied to single- or paired-end reads, we identified 438 genes expressing 813 different FTs in the NAc. Although all types of studied repeats were present in FTs, simple sequence repeats were underrepresented. Most importantly, reverse-transcription and quantitative PCR validated the expression of selected FTs in an independent cohort of animals, which also revealed that some FTs are the prominent isoforms expressed in the NAc by some genes. In other RNA-seq datasets, developmental expression as well as tissue specificity of some FTs differed from their corresponding non-fusion counterparts. Finally, in silico analysis predicted changes in the structure of proteins encoded by some FTs, potentially resulting in gain or loss of function. Collectively, these results indicate the robustness of our pipeline in detecting these new isoforms of genes, which we believe provides a valuable tool to aid in better understanding the broad role of REs in mammalian cellular biology. PMID:27415830

  6. Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome.

    Science.gov (United States)

    Jacobs, Damon T; Silva, Luciane M; Allard, Bailey A; Schonfeld, Michael P; Chatterjee, Anindita; Talbott, George C; Beier, David R; Tran, Pamela V

    2016-07-01

    Primary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139) encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc) was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp) expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease. PMID:27482817

  7. 胰高血糖素样肽-1与下丘脑食欲调节%Glucagon-like peptide-1 and appetite regulation in the hypothalamus

    Institute of Scientific and Technical Information of China (English)

    陈瑶; 郗光霞

    2012-01-01

    Hypothalamus is the center of neuroendocrine and appetite-regulation.Glucagons-like peptide-1 (GLP-1) is an incretin which is expressed in the hypothalamus,and regulates the appetite center.GLP-1 is considered as an anorexia-peptide and reduces food intake via negative feedback signal within the hypothalamus.The important pathways of controlling appetite are corticotrophin-releasing hormone ( CRH ),histamine,neuropeptide Y/agouti-related protein ( NPY/AgRP),pro-opiomelanocortin/cocaine and amphetamine regulated transcript (POMC/CART) and AMP-activated protein kinase (AMPK).Research on the mechanism of GLP-1 appetite-regulation may provide evidences on the treatment and prevention of obesity,insulin resistance and type 2 diabetes mellitus.%下丘脑是神经内分泌中枢,也是食欲调节中枢.胰高血糖素样肽-1(GLP-1)是一种胃肠道激素,能够在下丘脑表达并对食欲中枢有调节作用.GLP-1作为一种厌食信号肽,通过促肾上腺皮质激素释放激素(CRH)通路、组胺神经元通路、神经肽和刺鼠相关蛋白(NPY/AgRP)以及前阿片黑皮质素原和可卡因-苯丙胺调节转录肽(POMC/CART)通路及AMP活化蛋白激酶(AMPK)介导的摄食负反馈信号通路参与调节摄食活动.针对GLP-1调节摄食作用机制的研究对肥胖、胰岛素抵抗和2型糖尿病的防治有重要的理论意义.

  8. Prey preferences of the jaguar Panthera onca reflect the post-Pleistocene demise of large prey.

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    Matt W Hayward

    2016-01-01

    Full Text Available Documenting the impacts of the Pleistocene megafaunal extinctions on predator-prey interactions is a challenge because of the incomplete fossil record and depauperate extant community structure. We used a comparative ecological approach to investigate whether the existing prey preference patterns of jaguars Panthera onca were potentially affected by the Pleistocene extinctions in the Americas compared with large felids in Africa and Asia. We reviewed the literature and found 25 studies reporting 3214 jaguar kills recorded throughout the species’ distribution. We found that jaguars significantly preferred capybara Hydrochaeris hydrochaeris and giant anteater Myrmecophaga tridactyla, and avoided agoutis, carnivorans, primates, black-eared opossum Didelphis marsupialis and tapirs. Generalised linear models showed that jaguars select prey primarily based on socio-ecological and behavioural traits (abundance and herd size, rather than morphological characteristics (body size. Nonetheless, their accessible prey weight range was 6-60 kg, preferred prey weight range was 45-85 kg, and mean mass of significantly preferred prey was 32 ± 13 kg leading to a predator to prey body mass ratio of 1:0.53, which is much less than that of other solitary felids. Compared with other large, solitary felids, jaguars have an unusual predator to prey body mass ratio, show limited effect of prey morphology as a driver of prey selection, lack evidence of optimal foraging beyond their preferred prey, and an absence of preferentially hunting on Cetartiodactyla herbivores. These features, coupled with the reduction in jaguar body mass since the Pleistocene, suggest that the loss of larger potential prey items within the preferred and accessible weight ranges at the end-Pleistocene still affects jaguar predatory behaviour. It may be that jaguars survived this mass extinction event by preferentially preying on relatively small species.

  9. Nitric Oxide Exerts Basal and Insulin-Dependent Anorexigenic Actions in POMC Hypothalamic Neurons.

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    Wellhauser, Leigh; Chalmers, Jennifer A; Belsham, Denise D

    2016-04-01

    The arcuate nucleus of the hypothalamus represents a key center for the control of appetite and feeding through the regulation of 2 key neuronal populations, notably agouti-related peptide/neuropeptide Y and proopimelanocortin (POMC)/cocaine- and amphetamine-regulated transcript neurons. Altered regulation of these neuronal networks, in particular the dysfunction of POMC neurons upon high-fat consumption, is a major pathogenic mechanism involved in the development of obesity and type 2 diabetes mellitus. Efforts are underway to preserve the integrity or enhance the functionality of POMC neurons in order to prevent or treat these metabolic diseases. Here, we report for the first time that the nitric oxide (NO(-)) donor, sodium nitroprusside (SNP) mediates anorexigenic actions in both hypothalamic tissue and hypothalamic-derived cell models by mediating the up-regulation of POMC levels. SNP increased POMC mRNA in a dose-dependent manner and enhanced α-melanocortin-secreting hormone production and secretion in mHypoA-POMC/GFP-2 cells. SNP also enhanced insulin-driven POMC expression likely by inhibiting the deacetylase activity of sirtuin 1. Furthermore, SNP enhanced insulin-dependent POMC expression, likely by reducing the transcriptional repression of Foxo1 on the POMC gene. Prolonged SNP exposure prevented the development of insulin resistance. Taken together, the NO(-) donor SNP enhances the anorexigenic potential of POMC neurons by promoting its transcriptional expression independent and in cooperation with insulin. Thus, increasing cellular NO(-) levels represents a hormone-independent method of promoting anorexigenic output from the existing POMC neuronal populations and may be advantageous in the fight against these prevalent disorders. PMID:26930171

  10. The MC1R and ASIP Coat Color Loci May Impact Behavior in the Horse.

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    Jacobs, Lauren N; Staiger, Elizabeth A; Albright, Julia D; Brooks, Samantha A

    2016-05-01

    Shared signaling pathways utilized by melanocytes and neurons result in pleiotropic traits of coat color and behavior in many mammalian species. For example, in humans polymorphisms at MC1R cause red hair, increased heat sensitivity, and lower pain tolerance. In deer mice, rats, and foxes, ASIP polymorphisms causing black coat color lead to more docile demeanors and reduced activity. Horse (Equus caballus) base coat color is primarily determined by polymorphisms at the Melanocortin-1 Receptor (MC1R) and Agouti Signaling Protein (ASIP) loci, creating a black, bay, or chestnut coat. Our goal was to investigate correlations between genetic loci for coat color and temperament traits in the horse. We genotyped a total of 215 North American Tennessee Walking Horses for the 2 most common alleles at the MC1R (E/e) and ASIP (A/a) loci using previously published PCR and RFLP methods. The horses had a mean age of 10.5 years and comprised 83 geldings, 25 stallions, and 107 mares. To assess behavior, we adapted a previously published survey for handlers to score horses from 1 to 9 on 20 questions related to specific aspects of temperament. We utilized principle component analysis to combine the individual survey scores into 4 factors of variation in temperament phenotype. A factor component detailing self-reliance correlated with genotypes at the ASIP locus; black mares (aa) were more independent than bay mares (A_) (P = 0.0063). These findings illuminate a promising and novel animal model for future study of neuroendocrine mechanisms in complex behavioral phenotypes. PMID:26884605

  11. Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice.

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    Liu, Yang; Huang, Ying; Liu, Tiemin; Wu, Hua; Cui, Huxing; Gautron, Laurent

    2016-06-01

    Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia. PMID:27111742

  12. Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation.

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    Stéphanie Lacotte

    Full Text Available Liver transplantation for hepatocellular carcinoma (HCC results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01, increased liver function tests (p<0.01, the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005, which was related to an increased natural killer (NK cell frequency (p<0.05 and a higher monocyte/macrophage activation level (p<0.01. Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005, and liver monocyte/macrophage activation levels (p<0.01 were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05 and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor.

  13. Modulation of orexigenic and anorexigenic peptides gene expression in the rat DVC and hypothalamus by acute immobilization stress

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    Fatiha eChigr

    2014-07-01

    Full Text Available We studied the long term effects of a single exposure to immobilization stress (IS (1 hour on the expression of anorexigenic (Pro-opiomelanocortin: POMC and cocaine amphetamine related transcript: CART and orexigenic (neuropeptide Y:NPY, Agouti related peptide: AgRP factors in hypothalamus and dorso vagal complex (DVC. We showed, by using RT-PCR that in the hypothalamus, that the mRNAs of POMC and CART were up-regulated at the end of IS and up to 24 hours. This up regulation persists until 48-72h after IS for CART only. In the DVC, their expressions peak significantly at 24h post stress and decline afterwards; CART mRNA is down regulated after 48h post stress. NPY and AgRP mRNAs show a gradual increase just after the end of IS. The up regulation is significant only at 24 hours after stress for AgRP but remains significantly higher for NPY compared to controls. In DVC, the mRNAs of the two factors show generally a similar post stress pattern. A significant increase jut after the end of IS of rats which persists up to 24 hours after is firstly noticed. The levels tend then to reach the basal levels although, they were slightly but significantly higher up to 72 hours after stress for mRNA NPY. The comparison between the expression profiles of anorexigenic and the two orexigenic peptides investigated shows the presence of a parallelism between that of POMC and AgRP and that of CART and NPY when each brain region (hypothalamus and DVC is considered separately. It seems that any surge in the expression of each anorexigenic factor stimulates the expression of those of corresponding and appropriated orexigenic one. These last reactions from orexigenic peptides tend to attenuate the anorexigenic effects of CART and POMC and by consequent to abolish the anorexia state generated by stress.

  14. Lateral hypothalamic melanocortin receptor signaling modulates binge-like ethanol drinking in C57BL/6J mice.

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    Sprow, Gretchen M; Rinker, Jennifer A; Lowery-Gointa, Emily G; Sparrow, Angela M; Navarro, Montserrat; Thiele, Todd E

    2016-07-01

    Binge ethanol drinking is a highly pervasive and destructive behavior yet the underlying neurobiological mechanisms remain poorly understood. Recent work suggests that overlapping neurobiological mechanisms modulate feeding disorders and excessive ethanol intake, and converging evidence indicates that the melanocortin (MC) system may be a promising candidate. The aims of the present work were to examine how repeated binge-like ethanol drinking, using the 'drinking in the dark' (DID) protocol, impacts key peptides within the MC system and if site-specific manipulation of MC receptor (MCR) signaling modulates binge-like ethanol drinking. Male C57BL/6J mice were exposed to one, three or six cycles of binge-like ethanol, sucrose or water drinking, after which brain tissue was processed via immunohistochemistry (IHC) for analysis of key MC peptides, including alpha-melanocyte stimulating hormone (α-MSH) and agouti-related protein (AgRP). Results indicated that α-MSH expression was selectively decreased, while AgRP expression was selectively increased, within specific hypothalamic subregions following repeated binge-like ethanol drinking. To further explore this relationship, we used site-directed drug delivery techniques to agonize or antagonize MCRs within the lateral hypothalamus (LH). We found that the nonselective MCR agonist melanotan-II (MTII) blunted, while the nonselective MCR antagonist AgRP augmented, binge-like ethanol consumption when delivered into the LH. As these effects were region-specific, the present results suggest that a more thorough understanding of the MC neurocircuitry within the hypothalamus will help provide novel insight into the mechanisms that modulate excessive binge-like ethanol intake and may help uncover new therapeutic targets aimed at treating alcohol abuse disorders. PMID:25975524

  15. Targeting central melanocortin receptors: a promising novel approach for treating alcohol abuse disorders

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    Jeffrey eOlney

    2014-06-01

    Full Text Available The melanocortin (MC peptides are produced centrally by propiomelanocortin (POMC neurons within the arcuate nucleus of the hypothalamus and act through five seven-transmembrane G-protein coupled melanocortin receptor (MCR subtypes. The MC3R and MC4R subtypes, the most abundant central MCRs, are widely expressed in brain regions known to modulate neurobiological responses to ethanol, including regions of the hypothalamus and extended amygdala. Agouti-related protein (AgRP, also produced in the arcuate nucleus, is secreted in terminals expressing MCRs and functions as an endogenous MCR antagonist. This review highlights recent genetic and pharmacological findings that have implicated roles for the MC and AgRP systems in modulating ethanol consumption. Ethanol consumption is associated with significant alterations in the expression levels of various MC peptides/protein, which suggests that ethanol-induced perturbations of MC/AgRP signaling may modulate excessive ethanol intake. Consistently, MCR agonists decrease, and AgRP increases, ethanol consumption in mice. MCR agonists fail to blunt ethanol intake in mutant mice lacking the MC4R, suggesting that the protective effects of MCR agonists are modulated by the MC4R. Interestingly, recent evidence reveals that MCR agonists are more effective at blunting binge-like ethanol intake in mutant mice lacking the MC3R, suggesting that the MC3R has opposing effects on the MC4R. Finally, mutant mice lacking AgRP exhibit blunted voluntary and binge-like ethanol drinking, consistent with pharmacological studies. Collectively, these preclinical observations provide compelling evidence that compounds that target the MC system may provide therapeutic value for treating alcohol abuse disorders and that the utilization of currently available MC-targeting compounds- such as those being used to treat eating disorders- may be used as effective treatments to this end.

  16. Inhibition of melanocortin 1 receptor slows melanoma growth, reduces tumor heterogeneity and increases survival.

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    Kansal, Rita G; McCravy, Matthew S; Basham, Jacob H; Earl, Joshua A; McMurray, Stacy L; Starner, Chelsey J; Whitt, Michael A; Albritton, Lorraine M

    2016-05-01

    Melanoma risk is increased in patients with mutations of melanocortin 1 receptor (MC1R) yet the basis for the increased risk remains unknown. Here we report in vivo evidence supporting a critical role for MC1R in regulating melanoma tumor growth and determining overall survival time. Inhibition of MC1R by its physiologically relevant competitive inhibitor, agouti signaling protein (ASIP), reduced melanin synthesis and morphological heterogeneity in murine B16-F10 melanoma cells. In the lungs of syngeneic C57BL/6 mice, mCherry-marked, ASIP-secreting lung tumors inhibited MC1R on neighboring tumors lacking ASIP in a dose dependent manner as evidenced by a proportional loss of pigment in tumors from mice injected with 1:1, 3:1 and 4:1 mixtures of parental B16-F10 to ASIP-expressing tumor cells. ASIP-expressing B16-F10 cells formed poorly pigmented tumors in vivo that correlated with a 20% longer median survival than those bearing parental B16-F10 tumors (p=0.0005). Mice injected with 1:1 mixtures also showed survival benefit (p=0.0054), whereas injection of a 4:1 mixture showed no significant difference in survival. The longer survival time of mice bearing ASIP-expressing tumors correlated with a significantly slower growth rate than parental B16-F10 tumors as judged by quantification of numbers of tumors and total tumor load (p=0.0325), as well as a more homogeneous size and morphology of ASIP-expressing lung tumors. We conclude that MC1R plays an important role in regulating melanoma growth and morphology. Persistent inhibition of MC1R provided a significant survival advantage resulting in part from slower tumor growth, establishing MC1R as a compelling new molecular target for metastatic melanoma. PMID:27028866

  17. Central melanocortins regulate the motivation for sucrose reward.

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    Rahul Pandit

    Full Text Available The role of the melanocortin (MC system in feeding behavior is well established. Food intake is potently suppressed by central infusion of the MC 3/4 receptor agonist α-melanocyte stimulating hormone (α-MSH, whereas the MC 3/4 receptor inverse-agonist Agouti Related Peptide (AGRP has the opposite effect. MC receptors are widely expressed in both hypothalamic and extra-hypothalamic brain regions, including nuclei involved in food reward and motivation, such as the nucleus accumbens (NAc and the ventral tegmental area. This suggests that MCs modulate motivational aspects of food intake. To test this hypothesis, rats were injected intracerebroventricularly with α-MSH or AGRP and their motivation for sucrose was tested under a progressive ratio schedule of reinforcement. Food motivated behavior was dose-dependently decreased by α-MSH. Conversely, AGRP increased responding for sucrose, an effect that was blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. In contrast to progressive ratio responding, free intake of sucrose remained unaltered upon α-MSH or AGRP infusion. In addition, we investigated whether the effects of α-MSH and AGRP on food motivation were mediated by the NAc shell. In situ hybridization of MC3 and MC4 receptor expression confirmed that the MC4 receptor was expressed throughout the NAc, and injection of α-MSH and AGRP into the NAc shell caused a decrease and an increase in motivation for sucrose, respectively. These data show that the motivation for palatable food is modulated by MC4 receptors in the NAc shell, and demonstrate cross-talk between the MC and dopamine system in the modulation of food motivation.

  18. Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester ester nanovector induces donor-specific liver allograft tolerance

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    Hu F

    2015-07-01

    Full Text Available Fanguo Hu,1,* Hanjie Wang,2,* Shuangnan Zhang,2 Yao Peng,2 Lin Su,2 Jin Chang,2 Gang Liu11Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2School of Life Sciences, Tianjin University, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin, People’s Republic of China*These authors contributed equally to this workAbstract: Toll-like receptors (TLRs activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell maturation and initiation of adaptive immune responses that provoke allograft rejection. We aimed to prolong allograft survival by selectively inhibiting expression of myeloid differentiation factor 88 (MyD88, which is an essential adaptor in TLR signaling. We designed and synthesized a novel histidine-grafted poly(β-amino ester(HGPAE nanovector, which was shown to be safe and efficient both in vitro and in vivo for the delivery of a plasmid containing shRNA targeting MyD88 (pMyD88. We also demonstrated that the pMyD88/HGPAE complex mediated remarkable inhibition of MyD88 expression in rat liver in vivo. We transplanted Dark Agouti rat livers lacking MyD88 as result of transfection with the pMyD88/HGPAE complex into Lewis rats. The recipients survived longer and graft rejection of the donor liver as well as serum levels of IL-2 and IFN-γ in the recipient were significantly reduced.Keywords: immune recognition, allograft rejection, MyD88, short hairpin RNA (shRNA, gene delivery, PAE

  19. Colocalization of cocaine- and amphetamine-regulated transcript with kisspeptin and neurokinin B in the human infundibular region.

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    Katalin Skrapits

    Full Text Available Kisspeptin (KP- and neurokinin B (NKB- synthesizing neurons of the hypothalamic arcuate nucleus play a pivotal role in the regulation of pulsatile gonadotropin-releasing hormone (GnRH secretion. Unlike in rodents and sheep, the homologous KP and NKB neurons in the human infundibular region rarely express dynorphin- but often exhibit Substance P (SP immunoreactivity, indicating remarkable species differences in the neurochemical phenotype of these neurons. In search for additional neuropeptides in human KP and NKB neurons, we carried out immunofluorescent studies on hypothalamic sections obtained from five postmenopausal women. Colocalization experiments provided evidence for the presence of cocaine- and amphetamine-regulated transcript (CART in 47.9 ± 6.6% of KP-immunoreactive (IR and 30.0 ± 4.9% of NKB-IR perikarya and in 17.0 ± 2.3% of KP-IR and 6.2 ± 2.0% of NKB-IR axon varicosities. All three neuropeptides were present in 33.3 ± 4.9% of KP-IR and 28.2 ± 4.6% of NKB-IR somata, respectively, whereas triple-labeling showed lower incidences in KP-IR (14.3 ± 1.8% and NKB-IR (5.9 ± 2.0% axon varicosities. CART-IR KP and NKB neurons established contacts with other peptidergic cells, including GnRH-IR neurons and also sent projections to the infundibular stalk. KP and NKB fibers with CART often contained SP as well, while being distinct from CART fibers co-containing the orexigenic peptide agouti-related protein. Presence of CART in human, but not rodent, KP and NKB neurons represents a new example of species differences in the neuropeptide repertoire of mediobasal hypothalamic KP and NKB neurons. Target cells, receptor sites and physiological significance of CART in the efferent communication of KP and NKB neurons in primates require clarification.

  20. Diurnal profiles of hypothalamic energy balance gene expression with photoperiod manipulation in the Siberian hamster, Phodopus sungorus.

    Science.gov (United States)

    Ellis, Claire; Moar, Kim M; Logie, Tracy J; Ross, Alexander W; Morgan, Peter J; Mercer, Julian G

    2008-04-01

    Hypothalamic energy balance genes have been examined in the context of seasonal body weight regulation in the Siberian hamster. Most of these long photoperiod (LD)/short photoperiod (SD) comparisons have been of tissues collected at a single point in the light-dark cycle. We examined the diurnal expression profile of hypothalamic genes in hamsters killed at 3-h intervals throughout the light-dark cycle after housing in LD or SD for 12 wk. Gene expression of neuropeptide Y, agouti-related peptide, proopiomelanocortin, cocaine- and amphetamine-regulated transcript, long-form leptin receptor, suppressor of cytokine signaling-3, melanocortin-3 receptor, melanocortin-4 receptor, and the clock gene Per1 as control were measured by in situ hybridization in hypothalamic nuclei. Effects of photoperiod on gene expression and leptin levels were generally consistent with previous reports. A clear diurnal variation was observed for Per1 in the suprachiasmatic nucleus in both photoperiods. Temporal effects on expression of energy balance genes were restricted to long-form leptin receptor in the arcuate nucleus and ventromedial nucleus, where similar diurnal expression profiles were observed, and melanocortin-4 receptor in the paraventricular nucleus; these effects were only observed in LD hamsters. There was no variation in serum leptin concentration. The 24-h profiles of hypothalamic energy balance gene expression broadly confirm photoperiodic differences that were observed previously, based on single time point comparisons, support the growing consensus that these genes have a limited role in seasonal body weight regulation, and further suggest limited involvement in daily rhythms of food intake.

  1. A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq

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    Feng, Jian; Fargo, David C.; Shen, Li; Riadi, Gonzalo; Keeley, Elizabeth; Rosh, Zachary S.; Nestler, Eric J.; Woychik, Richard P.

    2016-01-01

    Repetitive elements (REs) comprise 40–60% of the mammalian genome and have been shown to epigenetically influence the expression of genes through the formation of fusion transcript (FTs). We previously showed that an intracisternal A particle forms an FT with the agouti gene in mice, causing obesity/type 2 diabetes. To determine the frequency of FTs genome-wide, we developed a TopHat-Fusion-based analytical pipeline to identify FTs with high specificity. We applied it to an RNA-seq dataset from the nucleus accumbens (NAc) of mice repeatedly exposed to cocaine. Cocaine was previously shown to increase the expression of certain REs in this brain region. Using this pipeline that can be applied to single- or paired-end reads, we identified 438 genes expressing 813 different FTs in the NAc. Although all types of studied repeats were present in FTs, simple sequence repeats were underrepresented. Most importantly, reverse-transcription and quantitative PCR validated the expression of selected FTs in an independent cohort of animals, which also revealed that some FTs are the prominent isoforms expressed in the NAc by some genes. In other RNA-seq datasets, developmental expression as well as tissue specificity of some FTs differed from their corresponding non-fusion counterparts. Finally, in silico analysis predicted changes in the structure of proteins encoded by some FTs, potentially resulting in gain or loss of function. Collectively, these results indicate the robustness of our pipeline in detecting these new isoforms of genes, which we believe provides a valuable tool to aid in better understanding the broad role of REs in mammalian cellular biology. PMID:27415830

  2. Glutamate and GABA in appetite regulation

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    Teresa Cardoso Delgado

    2013-08-01

    Full Text Available Appetite is regulated by a coordinated interplay between gut, adipose tissue and brain. A primary site for the regulation of appetite is the hypothalamus where interaction between orexigenic neurons, expressing Neuropeptide Y/Agouti-related protein, and anorexigenic neurons, expressing Pro-opiomelanocortin cocaine/Amphetamine-related transcript, controls energy homeostasis. Within the hypothalamus, several peripheral signals have been shown to modulate the activity of these neurons, including the orexigenic peptide ghrelin and the anorexigenic hormones insulin and leptin. In addition to the accumulated knowledge on neuropeptide signaling, presence and function of amino acid neurotransmitters in key hypothalamic neurons brought a new light into appetite regulation. Therefore, the principal aim of this review will be to describe the current knowledge of the role of amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation and the associated neuronal-astrocytic metabolic coupling mechanisms.Glutamate and GABA dominate synaptic transmission in the hypothalamus and administration of their receptors agonists into hypothalamic nuclei stimulates feeding. By using 13C High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance spectroscopy based analysis, the Cerdán group has shown that increased neuronal firing in mice hypothalamus, as triggered by appetite during the feeding-fasting paradigm, may stimulate the use of lactate as neuronal fuel leading to increased astrocytic glucose consumption and glycolysis. Moreover, fasted mice showed increased hypothalamic [2-13C]GABA content, which may be explained by the existence of GABAergic neurons in key appetite regulation hypothalamic nuclei. Interestingly, increased [2-13C]GABA concentration in the hypothalamus of fasted animals appears to result mainly from reduction in GABA metabolizing pathways, rather than increased GABA synthesis by augmented activity of the

  3. Endotoxemia-induced muscle wasting is associated with the change of hypothalamic neuropeptides in rats.

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    Duan, Kaipeng; Yu, Wenkui; Lin, Zhiliang; Tan, Shanjun; Bai, Xiaowu; Gao, Tao; Xi, Fengchan; Li, Ning

    2014-12-01

    In critical patients, sepsis-induced muscle wasting is considered to be an important contributor to complications and mortality. Previous work mainly focuses on the peripheral molecular mechanism of muscle degradation, however little evidence exists for the role of central nervous system in the process. In the present study, we, for the first time, characterized the relationship between muscle wasting and central neuropeptide changes in a septic model. Thirty-six adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) or saline. Twelve, 24 and 48 hrs after injection, skeletal muscle and hypothalamus tissues were harvested. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle ring finger 1 (MuRF-1) and muscle atrophy F-box (MAFbx), as well as 3-methyl-histidine (3-MH) and tyrosine release. Hypothalamic neuropeptides and inflammatory marker expressions were also measured in three time points. LPS injection caused an increase expression of MuRF-1 and MAFbx, and a significant higher release of 3-MH and tyrosine. Hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), agouti-related protein (AgRP) and neuropeptide Y (NPY) presented a dynamic change after LPS injection. Also, hypothalamic inflammatory markers, interleukin-1 β (IL-1β) and tumor necrosis factor α (TNF-α) increased substantially after LPS administration. Importantly, the expressions of POMC, AgRP and CART were well correlated with muscle atrophy gene, MuRF-1 expression. These findings suggest hypothalamic peptides and inflammation may participate in the sepsis-induced muscle wasting, but the exact mechanism needs further study.

  4. The expression of leptin, hypothalamic neuropeptides and UCP1 before, during and after fattening in the Daurian ground squirrel (Spermophilus dauricus).

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    Xing, Xin; Yang, Ming; Wang, De-Hua

    2015-06-01

    The Daurian ground squirrel (Spermophilus dauricus) accumulates large amounts of body fat during pre-hibernation fattening. Leptin, an adipose-derived hormone, plays important roles in energy balance and thermogenesis. We predicted that body fat accumulation would lead to the elevation of leptin concentration while its effect on satiety would be suppressed in hypothalamus during fattening. In addition, the uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) would increase and correlated positively with leptin concentration before hibernation. Here, we measured serum leptin concentration and leptin mRNA in white adipose tissue (WAT), hypothalamic neuropeptides involved in energy regulation and UCP1 in BAT before, during and after fattening in squirrels. The fat mass gradually increased during fattening but serum leptin increased mainly in the late phase of fattening, which was consistent with leptin mRNA expression in WAT. During fattening, the mRNA of hypothalamic leptin receptor was up-regulated and correlated positively with serum leptin. Orexigenic neuropeptide Y mRNA increased by 67%; however agouti-related peptide remained unchanged before hibernation. There was no significant change in anorexigenic neuropeptide mRNA. No change in suppressor of cytokine signaling-3 and protein tyrosine phosphatase-1B was detected. UCP1 mRNA expression and protein content in BAT increased significantly after fattening. These changes were independent of environmental conditions and serum leptin concentration. Our results suggest that the dissociation of leptin production and adiposity during fattening may facilitate fat accumulation. No evidence of suppressed leptin signal was found in fattening squirrels. The UCP1 recruitment in post-fattening squirrels could occur without winter-like acclimation and increased leptin.

  5. Litter size variation in hypothalamic gene expression determines adult metabolic phenotype in Brandt's voles (Lasiopodomys brandtii.

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    Xue-Ying Zhang

    Full Text Available BACKGROUND: Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10-12 and small (3-4 litter sizes, of Brandt's voles (Lasiopodomys brandtii, a rodent species from Inner Mongolia grassland in China. METHODOLOGY/PRINCIPAL FINDINGS: Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3 mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP mRNA increased in the offspring from small litters. CONCLUSIONS/SIGNIFICANCE: These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.

  6. Glucocorticoids are required for meal-induced changes in the expression of hypothalamic neuropeptides.

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    Uchoa, Ernane Torres; Silva, Lilian Eslaine C M; de Castro, Margaret; Antunes-Rodrigues, Jose; Elias, Lucila L K

    2012-06-01

    Glucocorticoid deficiency is associated with a decrease of food intake. Orexigenic peptides, neuropeptide Y (NPY) and agouti related protein (AgRP), and the anorexigenic peptide proopiomelanocortin (POMC), expressed in the arcuate nucleus of the hypothalamus (ARC), are regulated by meal-induced signals. Orexigenic neuropeptides, melanin-concentrating hormone (MCH) and orexin, expressed in the lateral hypothalamic area (LHA), also control food intake. Thus, the present study was designed to test the hypothesis that glucocorticoids are required for changes in the expression of hypothalamic neuropeptides induced by feeding. Male Wistar rats (230-280 g) were subjected to ADX or sham surgery. ADX animals received 0.9% NaCl in the drinking water, and half of them received corticosterone in the drinking water (B: 25 mg/L, ADX+B). Six days after surgery, animals were fasted for 16 h and they were decapitated before or 2 h after refeeding for brain tissue and blood collections. Adrenalectomy decreased NPY/AgRP and POMC expression in the ARC in fasted and refed animals, respectively. Refeeding decreased NPY/AgRP and increased POMC mRNA expression in the ARC of sham and ADX+B groups, with no effects in ADX animals. The expression of MCH and orexin mRNA expression in the LHA was increased in ADX and ADX+B groups in fasted condition, however there was no effect of refeeding on the expression of MCH and orexin in the LHA in the three experimental groups. Refeeding increased plasma leptin and insulin levels in sham and ADX+B animals, with no changes in leptin concentrations in ADX group, and insulin response to feeding was lower in this group. Taken together, these data demonstrated that circulating glucocorticoids are required for meal-induced changes in NPY, AgRP and POMC mRNA expression in the ARC. The lower leptin and insulin responses to feeding may contribute to the altered hypothalamic neuropeptide expression after adrenalectomy.

  7. Role of neuropeptides in appetite regulation and obesity--a review.

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    Arora, Sarika; Anubhuti

    2006-12-01

    Obesity represents the most prevalent nutritional problem worldwide which in the long run predisposes to development of diabetes mellitus, hypertension, endometrial carcinoma, osteoarthritis, gall stones and cardiovascular diseases. Despite significant reductions in dietary fat consumption, the prevalence of obesity is on a rise and is taking on pandemic proportions. Obesity develops when energy intake exceeds energy expenditure over time. Recently, a close evolutionary relationship between the peripheral and hypothalamic neuropeptides has become apparent. The hypothalamus being the central feeding organ mediates regulation of short-term and long-term dietary intake via synthesis of various orexigenic and anorectic neuropeptides. The structure and function of many hypothalamic peptides (neuropeptide Y (NPY), melanocortins, agouti-related peptide (AGRP), cocaine and amphetamine regulated transcript (CART), melanin concentrating hormone (MCH), orexins have been characterized in rodent models The peripheral neuropeptides such as cholecystokinin (CCK), ghrelin, peptide YY (PYY3-36), amylin, bombesin regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. The pharmacological potential of several endogenous peripheral peptides released prior to, during and/or after feeding are being explored. Long-term regulation is provided by the main circulating hormones leptin and insulin. These systems implicated in hypothalamic appetite regulation provide potential targets for treatment of obesity which could potentially pass into clinical development in the next 5 years. This review summarizes various effects and interrelationship of these central and peripheral neuropeptides in metabolism, obesity and their potential role as targets for treatment of obesity.

  8. Differential effect of prolonged food restriction and fasting on hypothalamic malonyl-CoA concentration and expression of orexigenic and anorexigenic neuropeptides genes in rats.

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    Sucajtys-Szulc, Elzbieta; Turyn, Jacek; Goyke, Elzbieta; Korczynska, Justyna; Stelmanska, Ewa; Slominska, Ewa; Smolenski, Ryszard T; Rutkowski, Boleslaw; Swierczynski, Julian

    2010-02-01

    Several lines of evidence suggest that malonyl-CoA in the hypothalamus plays an important role in monitoring and modulating body energy balance. In fasted state the level of malonyl-CoA concentration significantly decreases. Simultaneously, orexigenic neuropeptides (NPY - neuropeptide Y, AgRP - agouti-related peptide) genes are expressed at high level, whereas anorexigenic neuropeptides (CART - cocaine-and amphetamine-regulated transcript, POMC - proopiomelanocortin) genes are expressed at low level. When food intake resumes, opposite effect is observed. This study examined the effect of prolonged food restriction, common in humans trying to lose body weight on expression of orexigenic and anorexigenic neuropeptides genes and on malonyl-CoA content in rat whole hypothalamus. We observed an increase of NPY and AgRP mRNA levels in hypothalamus of rats kept on 30 days-long food restriction (50% of the amount of food consumed by controls). Simultaneously, a decrease of CART and POMC mRNA levels occurred. Refeeding caused a decrease in NPY and POMC mRNA levels without effect on AgRP and CART mRNA. Surprisingly, both prolonged food restriction and food restriction/refeeding caused the increase of malonyl-CoA level in whole hypothalamus. In contrast, fasting for 24h caused the decrease of malonyl-CoA level, which was associated with the up-regulation of NPY and AgRP genes expression and down-regulation of CART and POMC genes expression. After refeeding opposite effect was observed. These results indicate that prolonged food restriction and acute fasting, conditions in which energy expenditure exceeds intake, differentially affect malonyl-CoA concentration and similarly affect orexigenic and anorexigenic neuropeptide genes expression in whole rat hypothalamus.

  9. Plasticity in gastrointestinal morphology and enzyme activity in lactating striped hamsters (Cricetulus barabensis).

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    Zhang, Ji-Ying; Zhao, Xiao-Ya; Wen, Jing; Tan, Song; Zhao, Zhi-Jun

    2016-05-01

    In small mammals, marked phenotypic plasticity of digestive physiology has been shown to make it easier for them to cope with energetically stressful periods, such as lactation. It has been proposed that the capacity of the gut to digest and absorb food is not the limiting factor to sustained energy intake (SusEI) during peak lactation. In this study, plasticity in energy intake and gastrointestinal morphology was examined in striped hamsters at different stages of reproduction and when raising litters of different sizes. Mechanisms associated with digestive enzymes and neuroendocrine hormones underpinning the plasticity were also examined. Females significantly increased energy intake, digestibility, digestive tract mass and the activity of stomach pepsin and small intestine maltase, sucrase and aminopeptidase in peak lactation compared with the non-productive and post-lactating periods. Further, females raising large litters significantly increased energy intake, digestibility, gastrointestinal mass and activity of digestive enzymes, and weaned heavier offspring compared with those nursing small and medium litters, indicating that the significant plasticity of digestive physiology increased reproductive performance. Agouti-related protein (AgRP) mRNA expression in the hypothalamus was up-regulated significantly in females raising large litters relative to those raising small litters. Serum leptin levels, and mRNA expression of hypothalamus neuropeptide Y (NPY) and the anorexigenic neuropeptides pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) did not differ among females raising small, medium and large litters. Leptin levels in lactation may only reflect a state of energy balance rather than being the prime driver of hyperphagia. Some hypothalamic neuropeptides, such as NPY, POMC and CART, may be involved in the limits to the SusEI during lactation. PMID:26944487

  10. Inhibition by Artocarpus tonkinensis of the development of collagen-induced arthritis in rats.

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    Ngoc, D D T; Catrina, A I; Lundberg, K; Harris, H E; Ha, N T; Anh, P T; Larsson, P

    2005-03-01

    Extracts of the leaves and roots from the tree Artocarpus tonkinensis A Cheval (family Moraceae) are used in traditional Vietnamese medicine in order to treat backache as well as rheumatic joint diseases. We prepared an ethyl acetate (EtOAc) extract from this plant and tested its anti-inflammatory properties in an experimental arthritis model, collagen-induced arthritis (CIA). CIA was induced in Dark Agouti rats by means of immunization with collagen type II (CII) emulsified in incomplete Freund's adjuvant. Starting at the day of immunization, the rats were treated daily with intraperitoneal injections of Artocarpus extract. Arthritis progression was measured by means of clinical scoring of paws and anti-CII antibody titres were measured by means of ELISA. In vitro, lymph node (LN) cell cultures were treated with Artocarpus extract and the apoptosis-inducing effect was determined with FACS staining by using annexin V and propidium iodide as well as the TUNEL method. Treatment of the rats with Artocarpus extract decreased arthritis incidence and severity and delayed disease onset. When treatment was started after the onset of arthritis, a tendency towards arthritis amelioration was observed. In vitro, Artocarpus extract acted as a T-cell modulator, inhibiting mitogen-induced T-cell proliferation and inducing apoptosis of activated LN-derived lymphocytes. Thus, we have demonstrated that an EtOAc extract of Artocarpus, a plant traditionally used in Vietnamese folk medicine for treating arthritic conditions, has beneficial effects in an experimental arthritis model. This effect is likely to be T cell-dependent and mediated through apoptosis induction in activated cells.

  11. Abrogation of the immunosuppressive effect of donor spleen cells on renal allografts in the rat by irradiation or heat treatment

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    Cranston, D.; Wood, K.J.; Morris, P.J.

    1986-09-01

    In the donor-recipient strain combination Lewis (RT1l) to Dark Agouti (RT1a), indefinite renal allograft survival (MST greater than 100 days) was induced by pretreating recipient animals i.v. with 10(6) to 10(8) viable spleen lymphocytes, seven days before transplantation. Pretreatment with 10(4) or 10(5) cells was ineffective (MST 10 days). However when 10(7) live, but heat-treated (55 degrees C for 10 min) or irradiated (1000 rads) cells were used, all the animals rejected the allograft in a normal fashion (MST 10 and 11 days, respectively). Median survival time of third-party controls was 10 days. The relative amount of cell surface major histocompatibility antigens (class I and class II) expressed by the three spleen cell preparations was investigated using monoclonal antibodies and fluorescence activated cell sorter analysis and found to be similar. After 24 hr in culture, only 1% of heat-treated and 10% of irradiated cells were viable, in contrast to 75% of untreated splenocytes. Trafficking of these lymphocytes in recipient animals was investigated by 51chromium labeling of the cells: 30% of lymphocytes had localized in the liver within 3 hr with little difference in localization among the different cell preparations. But, although 20% of normal and irradiated cells localized in the spleen within 3 hr, at no stage were more than 5% of the heat-treated cells found in the spleen. It is suggested that the length of time viable donor lymphocytes remain in the recipient circulation is important in the induction of specific immunosuppression by spleen lymphocytes.

  12. Development of chronic allograft rejection and arterial hypertension in Brown Norway rats after renal transplantation.

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    Vaskonen, T; Mervaala, E; Nevala, R; Soots, A; Krogerus, L; Lähteenmäki, T; Karppanen, H; Vapaatalo, H; Ahonen, J

    2000-01-01

    The cardiovascular and renal pathophysiology associated with chronic renal allograft rejection under triple drug immunosuppressive treatment was studied using a recently developed model (Brown Norway (BN) rats) in a 6-week experiment. Renal transplantation was performed to 10-week-old rats in a rat strain combination of Dark Agouti (DA) --> BN. The right kidney was removed from another group of BN rats (uninephrectomized). A triple drug treatment comprising cyclosporine (10 mg/kg subcutaneously, s.c.), azathioprine (2 mg/kg s.c.) and methylprednisolone (1.6 mg/kg s.c.) was given to each rat daily for 6 weeks. A control group underwent no operations nor drug treatment. After the transplantation, the systolic blood pressure in this group was increased from 116 +/- 2 to 166 +/- 2 mmHg, while in the uninephrectomized group the rise was from 115 +/- 4 to 146 +/- 4 mmHg, and no change was observed in the blood pressures of the control group. The vascular relaxation responses of mesenteric arterial rings in vitro to acetylcholine were inhibited in both the transplantation group and the uninephrectomized group as compared with the control group, but few significant differences were found in the contraction responses to noradrenaline and potassium chloride. Graft histology was examined after 6 weeks, quantified by using the chronic allograft damage index (CADI). Changes specific to a chronic rejection reaction were observed in the allografts (CADI mean 6.0) but no injuries were seen in the rats' own kidneys (CADI mean 1.2). Our findings show that allograft rejection in BN rats after renal transplantation is associated with the development of arterial hypertension. The combination of cyclosporine, methylprednisolone and azathioprine also rises blood pressure in uninephrectomized BN rats. The hypertensive effects of the drug treatment and graft rejection are associated with endothelial dysfunction.

  13. Third ventricular coinjection of subthreshold doses of NPY and AgRP stimulate food hoarding and intake and neural activation.

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    Teubner, Brett J W; Keen-Rhinehart, Erin; Bartness, Timothy J

    2012-01-01

    We previously demonstrated that 3rd ventricular (3V) neuropeptide Y (NPY) or agouti-related protein (AgRP) injection potently stimulates food foraging/hoarding/intake in Siberian hamsters. Because NPY and AgRP are highly colocalized in arcuate nucleus neurons in this and other species, we tested whether subthreshold doses of NPY and AgRP coinjected into the 3V stimulates food foraging, hoarding, and intake, and/or neural activation [c-Fos immunoreactivity (c-Fos-ir)] in hamsters housed in a foraging/hoarding apparatus. In the behavioral experiment, each hamster received four 3V treatments by using subthreshold doses of NPY and AgRP for all behaviors: 1) NPY, 2) AgRP, 3) NPY+AgRP, and 4) saline with a 7-day washout period between treatments. Food foraging, intake, and hoarding were measured 1, 2, 4, and 24 h and 2 and 3 days postinjection. Only when NPY and AgRP were coinjected was food intake and hoarding increased. After identical treatment in separate animals, c-Fos-ir was assessed at 90 min and 14 h postinjection, times when food intake (0-1 h) and hoarding (4-24 h) were uniquely stimulated. c-Fos-ir was increased in several hypothalamic nuclei previously shown to be involved in ingestive behaviors and the central nucleus of the amygdala (CeA), but only in NPY+AgRP-treated animals (90 min and 14 h: magno- and parvocellular regions of the hypothalamic paraventricular nucleus and perifornical area; 14 h only: CeA and sub-zona incerta). These results suggest that NPY and AgRP interact to stimulate food hoarding and intake at distinct times, perhaps released as a cocktail naturally with food deprivation to stimulate these behaviors.

  14. Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

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    Anne eDrougard

    2015-02-01

    Full Text Available Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC and agouti-related protein (AgRP/neuropeptide Y (NPY neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,..., neurotransmitters and nutrients (glucose, lipids,.... The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes.In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

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

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    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.

  16. Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY neuron neuropeptides in female mice.

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    Roa, Juan; Herbison, Allan E

    2012-11-01

    Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons act to sense and coordinate the brain's responses to metabolic cues. One neuronal network that is very sensitive to metabolic status is that controlling fertility. In this study, we investigated the impact of neuropeptides released by NPY and POMC neurons on the cellular excitability of GnRH neurons, the final output cells of the brain controlling fertility. The majority (∼70%) of GnRH neurons were activated by α-melanocyte-stimulating hormone, and this resulted from the direct postsynaptic activation of melanocortin receptor 3 and melanocortin receptor 4. A small population of GnRH neurons (∼15%) was excited by cocaine and amphetamine-regulated transcript or inhibited by β-endorphin. Agouti-related peptide, released by NPY neurons, was found to have variable inhibitory (∼10%) and stimulatory (∼25%) effects upon subpopulations of GnRH neurons. A variety of NPY and pancreatic polypeptide analogs was used to examine potential NPY interactions with GnRH neurons. Although porcine NPY (Y1/Y2/Y5 agonist) directly inhibited the firing of approximately 45% of GnRH neurons, [Leu(31),Pro(34)]-NPY (Y1/Y4/Y5 agonist) could excite (56%) or inhibit (19%). Experiments with further agonists indicated that Y1 receptors were responsible for suppressing GnRH neuron activity, whereas postsynaptic Y4 receptors were stimulatory. These results show that the activity of GnRH neurons is regulated in a complex manner by neuropeptides released by POMC and NPY neurons. This provides a direct route through which different metabolic cues can regulate fertility.

  17. Regulation of prolactin in mice with altered hypothalamic melanocortin activity.

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    Dutia, Roxanne; Kim, Andrea J; Mosharov, Eugene; Savontaus, Eriika; Chua, Streamson C; Wardlaw, Sharon L

    2012-09-01

    This study used two mouse models with genetic manipulation of the melanocortin system to investigate prolactin regulation. Mice with overexpression of the melanocortin receptor (MC-R) agonist, α-melanocyte-stimulating hormone (Tg-MSH) or deletion of the MC-R antagonist agouti-related protein (AgRP KO) were studied. Male Tg-MSH mice had lower blood prolactin levels at baseline (2.9±0.3 vs. 4.7±0.7ng/ml) and after restraint stress (68±6.5 vs. 117±22ng/ml) vs. WT (pprolactin content was not different. Blood prolactin was also decreased in male AgRP KO mice at baseline (4.2±0.5 vs. 7.6±1.3ng/ml) and after stress (60±4.5 vs. 86.1±5.7ng/ml) vs. WT (pprolactin content was lower in male AgRP KO mice (4.3±0.3 vs. 6.7±0.5μg/pituitary, pprolactin levels were observed in female AgRP KO mice vs. WT. Hypothalamic dopamine activity was assessed as the potential mechanism responsible for changes in prolactin levels. Hypothalamic tyrosine hydroxylase mRNA was measured in both genetic models vs. WT mice and hypothalamic dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content were measured in male AgRP KO and WT mice but neither were significantly different. However, these results do not preclude changes in dopamine activity as dopamine turnover was not directly investigated. This is the first study to show that baseline and stress-induced prolactin release and pituitary prolactin content are reduced in mice with genetic alterations of the melanocortin system and suggests that changes in hypothalamic melanocortin activity may be reflected in measurements of serum prolactin levels.

  18. The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia.

    Science.gov (United States)

    Dallmann, R; Weyermann, P; Anklin, C; Boroff, M; Bray-French, K; Cardel, B; Courdier-Fruh, I; Deppe, H; Dubach-Powell, J; Erb, M; Haefeli, R H; Henneböhle, M; Herzner, H; Hufschmid, M; Marks, D L; Nordhoff, S; Papp, M; Rummey, C; Santos, G; Schärer, F; Siendt, H; Soeberdt, M; Sumanovski, L T; Terinek, M; Mondadori, C; Güven, N; Feurer, A

    2011-09-01

    BACKGROUND: Under physiological conditions, the melanocortin system is a crucial part of the complex network regulating food intake and energy expenditure. In pathological states, like cachexia, these two parameters are deregulated, i.e., food intake is decreased and energy expenditure is increased-a vicious combination leading to catabolism. Agouti-related protein (AgRP), the endogenous antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food intake and to reduce energy expenditure. This qualifies MC-4R blockade as an attractive mode of action for the treatment of cachexia. Based on this rationale, a novel series of small-molecule MC-4R antagonists was designed, from which the orally active compound BL-6020/979 (formerly known as SNT207979) emerged as the first promising development candidate showing encouraging pre-clinical efficacy and safety properties which are presented here. METHODS AND RESULTS: BL-6020/979 is an orally available, selective and potent MC-4R antagonist with a drug-like profile. It increased food intake and decreased energy expenditure in healthy wild-type but not in MC-4R deficient mice. More importantly, it ameliorated cachexia-like symptoms in the murine C26 adenocarcinoma model; with an effect on body mass and body composition and on the expression of catabolic genes. Moreover, BL-6020/979 showed antidepressant-like properties in the chronic mild stress model in rats and exhibits a favorable safety profile. CONCLUSION: The properties of BL-6020/979 demonstrated in animal models and presented here make it a promising candidate suitable for further development towards a first-in-class treatment option for cachexia that potentially opens up the opportunity to treat two hallmarks of the disease, i.e., decreased food intake and increased energy expenditure, with one drug.

  19. Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions

    Institute of Scientific and Technical Information of China (English)

    Wei-kun HOU; Lie-su MENG; Fang ZHENG; Yu-rong WEN; Wen-hua ZHU; Cong-shan JIANG; Xiao-jing HE; Yan ZHOU; She-min LU

    2011-01-01

    Objective:This study was carried out to test the effects of methotrexate(MTX)and black seed oil(BSO)on pristane-induced arthritis(PIA)in rats.Methods:Inbred dark agouti(DA)rats were induced by a single subcutaneous injection of pristane,and then treated with MTX or BSO.Arthritis severity was evaluated macroscopic,ally and microscopically.Plasma nitric oxide(NO)concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-time reverse transcription-polymerase chain reaction(RT-PCR).Results:The clinical arthritis severity was decreased after MTX treatment,while the BSO groups did not show significant changes compared with the disease group.The plasma NO level of the MTX group was significantly decreased compared with the disease group,but the BSO groups showed no difference from the disease group in plasma NO levels.The interferon-γ(IFN-γ)and interleukin-17A(IL-17A)mRNA expressions in the spleens were significantly decreased in the MTX group,but only showed a declining trend in the BSO groups compared with the disease group.Neither MTX nor BSO had an effect on the mRNA expressions of IL-4,transforming growth factor β(TGF-β),and tumor necrosis factor-α(TNF-α)in the spleen.Conclusions:MTX,but not BSO,can reduce the arthritis severity and decrease the mRNA expressions of IFN-γ and IL-17A in pristane-induced arthritis of rats.

  20. Leptin regulates energy intake but fails to facilitate hibernation in fattening Daurian ground squirrels (Spermophilus dauricus).

    Science.gov (United States)

    Xing, Xin; Tang, Gang-Bin; Sun, Ming-Yue; Yu, Chao; Song, Shi-Yi; Liu, Xin-Yu; Yang, Ming; Wang, De-Hua

    2016-04-01

    Body fat storage before hibernation affects the timing of immergence in Daurian ground squirrels (Spermophilus dauricus). Leptin is an adipose signal and plays vital role in energy homeostasis mainly by action in brain. To test the hypothesis that leptin plays a role in facilitating the process of hibernation, squirrels were administrated with recombinant murine leptin (1μg/day) through intracerebroventricular (ICV) injection for 12 days during fattening. From day 7 to 12, animals were moved into a cold room (5±1°C) with constant darkness which functioned as hibernaculum. Energy intake, body mass and core body temperature (Tb) were continuously monitored throughout the course of experiment. Resting metabolic rate (RMR) was measured under both warm and cold conditions. At the end of leptin administration, we measured the serum concentration of hormones related to energy regulation, mRNA expression of hypothalamic neuropeptides and uncoupling protein 1 (UCP1) levels in brown adipose tissue (BAT). Our results showed that during leptin administration, the cumulative food intake and increase of body mass were suppressed while Tb and RMR were unaltered. The proportion of torpid squirrels was not different between two groups. At the end of leptin administration, the expressions of hypothalamic neuropeptide Y and agouti gene-related protein were suppressed. There were no differences in UCP1 mRNA expression or protein content in BAT between groups. Our data suggest that leptin can affect energy intake via hypothalamic neuropeptides, but is not involved in the initiation of hibernation in fattening Daurian ground squirrels. PMID:27033037

  1. Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying.

    Science.gov (United States)

    Janssen, Sara; Laermans, Jorien; Verhulst, Pieter-Jan; Thijs, Theo; Tack, Jan; Depoortere, Inge

    2011-02-01

    Ghrelin is a hunger hormone with gastroprokinetic properties but the factors controlling ghrelin secretion from the stomach are unknown. Bitter taste receptors (T2R) and the gustatory G proteins, α-gustducin (gust) and α-transducin, are expressed in the gut and are involved in the chemosensation of nutrients. This study aimed to investigate whether T2R-agonists affect (i) ghrelin release via α-gustducin and (ii) food intake and gastric emptying via the release of ghrelin. The mouse stomach contains two ghrelin cell populations: cells containing octanoyl and desoctanoyl ghrelin, which were colocalized with α-gustducin and α-transducin, and cells staining for desoctanoyl ghrelin. Gavage of T2R-agonists increased plasma octanoyl ghrelin levels in WT mice but the effect was partially blunted in gust(-/-) mice. Intragastric administration of T2R-agonists increased food intake during the first 30 min in WT but not in gust(-/-) and ghrelin receptor knockout mice. This increase was accompanied by an increase in the mRNA expression of agouti-related peptide in the hypothalamus of WT but not of gust(-/-) mice. The temporary increase in food intake was followed by a prolonged decrease (next 4 h), which correlated with an inhibition of gastric emptying. The delay in emptying, which was partially counteracted by ghrelin, was not mediated by cholecystokinin and GLP-1 but involved a direct inhibitory effect of T2R-agonists on gastric contractility. This study is unique in providing functional evidence that activation of bitter taste receptors stimulates ghrelin secretion. Modulation of endogenous ghrelin levels by tastants may provide novel therapeutic applications for the treatment of weight -and gastrointestinal motility disorders. PMID:21245306

  2. Redox regulation of apurinic/apyrimidinic endonuclease 1 activity in Long-Evans Cinnamon rats during spontaneous hepatitis.

    Science.gov (United States)

    Karmahapatra, Soumendra Krishna; Saha, Tapas; Adhikari, Sanjay; Woodrick, Jordan; Roy, Rabindra

    2014-03-01

    The Long-Evans Cinnamon (LEC) rat is an animal model for Wilson's disease. This animal is genetically predisposed to copper accumulation in the liver, increased oxidative stress, accumulation of DNA damage, and the spontaneous development of hepatocellular carcinoma. Thus, this animal model is useful for studying the relationship of endogenous DNA damage to spontaneous carcinogenesis. In this study, we have investigated the apurinic/apyrimidinic endonuclease 1 (APE1)-mediated excision repair of endogenous DNA damage, apurinic/apyrimidinic (AP)-sites, which is highly mutagenic and implicated in human cancer. We found that the activity was reduced in the liver extracts from the acute hepatitis period of LEC rats as compared with extracts from the age-matched Long-Evans Agouti rats. The acute hepatitis period had also a heightened oxidative stress condition as assessed by an increase in oxidized glutathione level and loss of enzyme activity of glyceraldehyde 3-phosphate dehydrogenase, a key redox-sensitive protein in cells. Interestingly, the activity reduction was not due to changes in protein expression but apparently by reversible protein oxidation as the addition of reducing agents to extracts of the liver from acute hepatitis period reactivated APE1 activity and thus, confirmed the oxidation-mediated loss of APE1 activity under increased oxidative stress. These findings show for the first time in an animal model that the repair mechanism of AP-sites is impaired by increased oxidative stress in acute hepatitis via redox regulation which contributed to the increased accumulation of mutagenic AP-sites in liver DNA.

  3. Effects of dietary fat types on body fatness, leptin, and ARC leptin receptor, NPY, and AgRP mRNA expression.

    Science.gov (United States)

    Wang, Hongqin; Storlien, Len H; Huang, Xu-Feng

    2002-06-01

    Some, but not all, fats are obesogenic. The aim of the present studies was to investigate the effects of changing type and amount of dietary fats on energy balance, fat deposition, leptin, and leptin-related neural peptides: leptin receptor, neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC), in C57Bl/6J mice. One week of feeding with a highly saturated fat diet resulted in ~50 and 20% reduction in hypothalamic arcuate NPY and AgRP mRNA levels, respectively, compared with a low-fat or an n-3 or n-6 polyunsaturated high-fat (PUFA) diet without change in energy intake, fat mass, plasma leptin levels, and leptin receptor or POMC mRNA. Similar neuropeptide results were seen at 7 wk, but by then epididymal fat mass and plasma leptin levels were significantly elevated in the saturated fat group compared with low-fat controls. In contrast, fat and leptin levels were reduced in the n-3 PUFA group compared with all other groups. At 7 wk, changing the saturated fat group to n-3 PUFA for 4 wk completely reversed the hyperleptinemia and increased adiposity and neuropeptide changes induced by saturated fat. Changing to a low-fat diet was much less effective. In summary, a highly saturated fat diet induces obesity without hyperphagia. A regulatory reduction in NPY and AgRP mRNA levels is unable to effectively counteract this obesogenic drive. Equally high fat diets emphasizing PUFAs may even protect against obesity.

  4. Hypothalamic neuropeptide expression following chronic food restriction in sedentary and wheel-running rats.

    Science.gov (United States)

    de Rijke, C E; Hillebrand, J J G; Verhagen, L A W; Roeling, T A P; Adan, R A H

    2005-10-01

    When rats are given access to a running-wheel in combination with food restriction, they will become hyperactive and decrease their food intake, a paradoxical phenomenon known as activity-based anorexia (ABA). Little is known about the regulation of the hypothalamic neuropeptides that are involved in the regulation of food intake and energy balance during the development of ABA. Therefore, rats were killed during the development of ABA, before they entered a state of severe starvation. Neuropeptide mRNA expression levels were analysed using quantitative real-time PCR on punches of separate hypothalamic nuclei. As is expected in a state of negative energy balance, expression levels of agouti-related protein (AgRP) and neuropeptide Y (NPY) were increased 5-fold in the arcuate nucleus (ARC) of food-restricted running ABA rats vs 2-fold in sedentary food-restricted controls. The co-regulated expression of AgRP and NPY strongly correlated with relative body weight and white adipose tissue mass. Arcuate expression of pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) was reduced 2-fold in the ABA group. In second-order neurons of the lateral hypothalamic area (LHA), melanin-concentrating hormone (MCH) mRNA expression was upregulated 2-fold in food-restricted running rats, but not in food-restricted sedentary controls. Prepro-orexin, CART and corticotropin-releasing hormone expression levels in the LHA and the paraventricular nucleus (PVN) were unchanged in both food-restricted groups. From this study it was concluded that during the development of ABA, neuropeptides in first-order neurons in the ARC and MCH in the LHA are regulated in an adequate response to negative energy balance, whereas expression levels of the other studied neuropeptides in secondary neurons of the LHA and PVN are unchanged and are probably regulated by factors other than energy status alone.

  5. Regulation of body mass and adiposity in the field vole, Microtus agrestis: a model of leptin resistance.

    Science.gov (United States)

    Król, Elzbieta; Speakman, John R

    2007-02-01

    Adult mammals are typically highly resistant to perturbations in their energy balance. In obese humans, however, this control appears to be lost. Apart from a few exceptional cases, this loss of control occurs despite appropriate levels of circulating leptin -- suggesting that elevated adiposity may be a consequence of failure to respond to the leptin signal: leptin resistance. When cold-acclimated male field voles (Microtus agrestis) are transferred from short (SD, 8 h light) to long (LD, 16 h light) photoperiods, they increase dramatically in body mass and fatness for about 4 weeks. After this period, their mass stabilizes at a new plateau about 25% higher than animals maintained in SD. The increase in adiposity is not caused by significant increases in food intake, but reflects an increase in digestive efficiency. Measures of circulating leptin reveal that the increased adiposity is matched by increased circulating leptin. By infusing voles with exogenous leptin, we have demonstrated that SD voles are leptin sensitive (reducing both body mass and food intake), whereas LD animals are leptin resistant. Voles may therefore be a useful model for understanding the process of leptin resistance. The change in leptin sensitivity in voles was not associated with changes in the levels of gene expression of the orexogenic or anorexogenic neuropeptides, such as neuropeptide Y, agouti-related peptide, POMC and cocaine- and amphetamine-regulated transcript, measured in the hypothalamic arcuate nucleus (ARC). During the phase that body mass was increasing, however, there was a transient increase in the ARC expression of suppressor of cytokine signalling-3 (SOCS3). These data suggest that the changes in the expression of SOCS3 in the ARC may be involved in leptin resistance. However, the mechanism by which these changes may be linked to alterations in digestive efficiency that underpin the changes in adiposity, or how the differences are signalled by changes in photoperiod

  6. Diet-induced obesity causes ghrelin resistance in reward processing tasks.

    Science.gov (United States)

    Lockie, Sarah H; Dinan, Tara; Lawrence, Andrew J; Spencer, Sarah J; Andrews, Zane B

    2015-12-01

    Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti-related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we hypothesized that DIO would also establish ghrelin resistance in the ventral tegmental area (VTA), a major site of dopaminergic cell bodies important in reward processing. We observed reduced sucrose and saccharin consumption in Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption relative to chow-fed controls. These data suggest that the deletion of ghrelin and high fat diet both cause anhedonia. To assess if these are causally related, we tested whether DIO caused ghrelin resistance in a classic model of drug reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were conditioned with ghrelin (1mg/kg in 10ml/kg ip) in the presence or absence of food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20mg/kg), indicating that they maintained the ability to develop conditioned behaviour. The absence of food availability during ghrelin conditioning sessions induced a conditioned place aversion, an effect that was still present in both chow and HFD mice. Bilateral intra-VTA ghrelin injection (0.33μg/μl in 0.5μl) robustly increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however, this was correlated with body weight only in the chow-fed mice. Our results suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We suggest there is impaired ghrelin sensitivity in upstream pathways regulating reward pathways, highlighting a functional role for ghrelin linking appropriate metabolic sensing with reward processing.

  7. The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

    Science.gov (United States)

    Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

    2016-02-01

    A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes.

  8. Evolution of alanine:glyoxylate aminotransferase 1 peroxisomal and mitochondrial targeting. A survey of its subcellular distribution in the livers of various representatives of the classes Mammalia, Aves and Amphibia.

    Science.gov (United States)

    Danpure, C J; Fryer, P; Jennings, P R; Allsop, J; Griffiths, S; Cunningham, A

    1994-08-01

    As part of a wider study on the molecular evolution of alanine:glyoxylate aminotransferase 1 (AGT1) intracellular compartmentalization, we have determined the subcellular distribution of immunoreactive AGT1, using postembedding protein A-gold immunoelectron microscopy, in the livers of various members of the classes Mammalia, Aves, and Amphibia. As far as organellar distribution is concerned, three categories could be distinguished. In members of the first category (type I), all, or nearly all, of the immunoreactive AGT1 was concentrated within the peroxisomes. In the second category (type II), AGT1 was found more evenly distributed in both peroxisomes and mitochondria. In the third category (type III), AGT1 was localized mainly within the mitochondria with much lower, but widely variable, amounts in the peroxisomes. Type I animals include the human, two great apes (gorilla, orangutan), two Old World monkeys (anubis baboon, Japanese macaque), a New World monkey (white-faced Saki monkey), a lago, morph (European rabbit), a bat (Seba's short-tailed fruit bat), two caviomorph rodents (guinea pig, orange-rumped agouti), and two Australian marsupials (koala, Bennett's wallaby). Type II animals include two New World monkeys (common marmoset, cotton-top tamarin), three prosimians (brown lemur, fat-tailed dwarf lemur, pygmy slow loris), five rodents (a hybrid crested porcupine, Colombian ground squirrel, laboratory rat, laboratory mouse, golden hamster), an American marsupial (grey short-tailed opossum), and a bird (raven). Type III animals include the large tree shrew, three insectivores (common Eurasian mole, European hedgehog, house shrew), four carnivores (domestic cat, ocelot, domestic dog, polecat ferret), and an amphibian (common frog). In addition to these categories, some animals (e.g. guinea pig, common frog) possessed significant amounts of cytosolic AGT1. Whereas the subcellular distribution of AGT1 in some orders (e.g. Insectivora and Carnivora) did not appear

  9. Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA: regulation by CB2 receptors and implications for neurotoxicity

    Directory of Open Access Journals (Sweden)

    O'Shea Esther

    2011-05-01

    Full Text Available Abstract Background 3,4-Methylenedioxymethamphetamine (MDMA produces a neuroinflammatory reaction in rat brain characterized by an increase in interleukin-1 beta (IL-1β and microglial activation. The CB2 receptor agonist JWH-015 reduces both these changes and partially protects against MDMA-induced neurotoxicity. We have examined MDMA-induced changes in IL-1 receptor antagonist (IL-1ra levels and IL-1 receptor type I (IL-1RI expression and the effects of JWH-015. The cellular location of IL-1β and IL-1RI was also examined. MDMA-treated animals were given the soluble form of IL-1RI (sIL-1RI and neurotoxic effects examined. Methods Dark Agouti rats received MDMA (12.5 mg/kg, i.p. and levels of IL-1ra and expression of IL-1RI measured 1 h, 3 h or 6 h later. JWH-015 (2.4 mg/kg, i.p. was injected 48 h, 24 h and 0.5 h before MDMA and IL-1ra and IL-1RI measured. For localization studies, animals were sacrificed 1 h or 3 h following MDMA and stained for IL-1β or IL-1RI in combination with neuronal and microglial markers. sIL-1RI (3 μg/animal; i.c.v. was administered 5 min before MDMA and 3 h later. 5-HT transporter density was determined 7 days after MDMA injection. Results MDMA produced an increase in IL-ra levels and a decrease in IL-1RI expression in hypothalamus which was prevented by CB2 receptor activation. IL-1RI expression was localized on neuronal cell bodies while IL-1β expression was observed in microglial cells following MDMA. sIL-1RI potentiated MDMA-induced neurotoxicity. MDMA also increased IgG immunostaining indicating that blood brain-barrier permeability was compromised. Conclusions In summary, MDMA produces changes in IL-1 signal modulators which are modified by CB2 receptor activation. These results indicate that IL-1β may play a partial role in MDMA-induced neurotoxicity.

  10. Effects of Pax3 modifier genes on craniofacial morphology, pigmentation, and viability: A murine model of Waardenburg syndrome variation

    Energy Technology Data Exchange (ETDEWEB)

    Asher, J.H. Jr.; Harrison, R.W.; Morell, R.; Carey, M.L. [Michigan State Univ., East Lansing, MI (United States)] [and others

    1996-06-15

    Waardenburg syndrome type 1 is caused by mutations in PAX3. Over 50 human PAX3 mutations that lead to hearing, craniofacial, limb, and pigmentation anomalies have been identified. A PAX3 mutant allele, segregating in a family, can show reduced penetrance and variable expressivity that cannot be explained by the nature of the mutation alone. The Mus musculus Pax3 mutation Sp{sup d} (Splotch-delayed, Pax3{sup Sd}p), coisogenic on the C57BL/6J (B{sub 6}) genetic background, produces in heterozygotes a white belly spot with 100% penetrance and very few other anomalies. By contrast, many Sp{sup d}/+ BC{sub 1} progeny [F{sub 1} {female} Sp{sup d}/+ ({female} Sp{sup d}/+ B{sub 6} x {male} +/+ Mus spretus) x {male} +/+ B{sub 6}] exhibit highly variable craniofacial and pigmentary anomalies. Of the BC{sub 1} Sp{sup d}/+ progeny, 23.9% are estimated to be nonviable, and 32.1% are nonpenetrant for the white belly spot. The penetrance and expressivity of the Sp{sup d}/+ genotype are controlled in part by the genetic background and the sex of the individual. A minimum of two genes interact with Sp{sup d} to influence the craniofacial features of these mice. One of these genes may be either X-linked or sex-influenced, while the other is autosomal. The A-locus (Agouti) or a gene closely linked to A also plays a role in determining craniofacial features. At least one additional gene, possibly the A-locus or a gene linked to A, interacts with Sp{sup d} and determines the presence and size of the white belly spot. The viability of BC{sub 1} mice is influenced by at least three factors: Sp{sup d}, A-locus alleles or a gene closely linked to the A-locus, and the sex of the mouse. The BC{sub 1} mice provide an opportunity to identify genes that interact with and modify the expression of Pax3 and serve as a model to identify the genes that modify the expression of human PAX3 mutations. 65 refs., 3 figs., 6 tabs.

  11. Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Jirtle, Randy L.

    2012-10-11

    The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (A{sup vy}) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure (<10 cGy) during early gestation. This information is particularly important to ascertain given the increased use of CT scans in disease diagnosis, increased number of people predicted to live and work in space, and the present concern about radiological terrorism. We showed for the first time that LDIR significantly increased DNA methylation at the A{sup vy} locus in a sex-specific manner (p=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic Avy mouse model epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in

  12. Epigenetic Effects of Environmental Chemicals Bisphenol A and Phthalates

    Directory of Open Access Journals (Sweden)

    Steven Shoei-Lung Li

    2012-08-01

    Full Text Available The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs of environmental chemicals such as bisphenol A (BPA and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1 promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues.

  13. Radiation-induced forward and reverse specific locus mutations and dominant cataract mutations in treated strain BALB/c and DBA/2 male mice.

    Science.gov (United States)

    Favor, J; Neuhäuser-Klaus, A; Ehling, U H

    1987-03-01

    Strain BALB/c and DBA/2 mice were chosen to investigate the effects of genetic background on the radiation-induced mutation rate since they exhibit differences in their radiation sensitivity. Males were exposed to 3 + 3-Gy X-irradiation and mated to untreated specific locus Test-stock females. Offspring resulting from treated spermatogonia were screened for induced specific locus forward and reverse mutations and dominant cataract mutations. Since BALB/c mice are homozygous brown and albino, specific locus forward mutations could be screened at 5 of the 7 specific loci (a, d, se, p, s), while reverse mutations could be screened at the b and c loci. Strain DBA/2 is homozygous non-agouti, brown and dilute. Therefore, specific locus forward mutations could be screened at 4 loci (c, se, p, s) and reverse mutations were screened at the a, b and d loci. Results indicate no effect of genetic background on the sensitivity to mutation induction of specific locus forward mutations, while for the dominant cataract alleles strain DBA/2 exhibited a higher mutation rate than either strain BALB/c or similarly treated (101/El X C3H/El)F1 mice. If, by confirmation, these differences should be demonstrated to be real, it is interesting that strain DBA/2 should exhibit a greater sensitivity to radiation-induced dominant mutations. First, strain DBA/2 was chosen as radiation resistant or repair competent. The observation that DBA/2 exhibited a higher sensitivity to radiation-induced mutation may indicate a role for repair, albeit misrepair, in the mutation process. Second, that the effect of genotype was only observed for the mutation rate to dominant cataract alleles may reflect a difference in the spectrum of DNA alterations which result in dominant or recessive alleles. A dominant allele is more likely misinformation, such that as heterozygote it interferes with the wild-type allele. By comparison, a recessive allele may result from any DNA alteration leading to the loss of a

  14. Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

    Science.gov (United States)

    Bajic, Juliana E; Eden, Georgina L; Lampton, Lorrinne S; Cheah, Ker Y; Lymn, Kerry A; Pei, Jinxin V; Yool, Andrea J; Howarth, Gordon S

    2016-01-01

    AIM To investigate the effects of orally gavaged aqueous rhubarb extract (RE) on 5-fluorouracil (5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats (n = 8/group) were gavaged daily (1 mL) with water, high-dose RE (HDR; 200 mg/kg) or low-dose RE (LDR; 20mg/kg) for eight days. Intestinal mucositis was induced (day 5) with 5-FU (150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase (MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS Bodyweight was significantly reduced in rats administered 5-FU compared to healthy controls (P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels (≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity (by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness (by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats (19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis. CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal

  15. Effect of residual feed intake on hypothalamic gene expression and meat quality in Angus-sired cattle grown during the hot season.

    Science.gov (United States)

    Perkins, S D; Key, C N; Marvin, M N; Garrett, C F; Foradori, C D; Bratcher, C L; Kriese-Anderson, L A; Brandebourg, T D

    2014-04-01

    The relationship between heat stress, meat quality, and residual feed intake (RFI) is unknown in growing steers. To address this issue, high RFI (HRFI) and low RFI (LRFI) individuals were compared by assessing RFI in 48 Angus-sired steers during a 70-d feeding trial conducted during July through September to identify steers with calculated RFI at least 2 SD apart. The association of RFI with indices of meat quality and expression of genes within hypothalamic and adipose tissue was then determined in LRFI and HRFI steers. While on test, feed intake was recorded daily with BW and hip heights recorded every 14 d. Ultrasound measurements of rib eye area (REA) and backfat (BF) were recorded initially and before harvest. Carcass and growth data were analyzed using a mixed model with RFI level (LRFI and HRFI) as the independent variable. The least square means for RFI were -1.2 and 0.99 kg DMI/d, respectively, for the LRFI and HRFI cohorts (P grade (P meat quality. Hypothalamic neuropeptide Y (NPY), agouti related protein (AGRP), relaxin-3 (RLN3), melanocortin 3 receptor, and relaxin/insulin-like family peptide receptor 1 (RXFP1) mRNA were expressed 280, 185, 202, 183, and 163% greater, respectively (P < 0.01), while proopiomelanocortin (POMC) mRNA was expressed 42% lower in LRFI than HRFI animals (P < 0.05). Hypothalamic GnRH mRNA expression was 67% lower while gonadotropin inhibiting hormone (GnIH) mRNA was 209% higher in LRFI than HRFI animals (P < 0.01). Pituitary expression of FSHβ and LHβ correlated to hypothalamic GnRH levels (P < 0.05) indicating changes in gene expression within the hypothalamus had functional consequences. Leptin mRNA expression levels were not different between adipose tissue of LRFI or HRFI steers (P < 0.84). These data indicate that animals with superior RFI evaluated during warm conditions have higher expression of orexigenic neuropeptide genes independent of the expression of adipose-derived leptin. Furthermore, the gonadotropin axis may

  16. Residual feed intake studies in Angus-sired cattle reveal a potential role for hypothalamic gene expression in regulating feed efficiency.

    Science.gov (United States)

    Perkins, S D; Key, C N; Garrett, C F; Foradori, C D; Bratcher, C L; Kriese-Anderson, L A; Brandebourg, T D

    2014-02-01

    Mechanisms underlying variation in residual feed intake (RFI), a heritable feed efficiency measure, are poorly understood while the relationship between RFI and meat quality is uncertain. To address these issues, 2 divergent cohorts consisting of High (HRFI) and Low (LRFI) RFI individuals were created by assessing RFI in 48 Angus-sired steers during a 70 d feeding trial to identify steers with divergent RFI. The association of RFI with indices of meat quality and expression of genes within hypothalamic and adipose tissue was then determined in LRFI and HRFI steers. While on test, feed intake was recorded daily with BW and hip heights recorded at 14 d intervals. Ultrasound measurements of rib eye area (REA) and backfat (BF) were recorded initially and before harvest. Carcass and growth data were analyzed using a mixed model with RFI level (LRFI, HRFI) as the independent variable. The least-square means (lsmeans) for RFI were -1.25 and 1.51 for the LRFI and HRFI cohorts (P grade (P meat quality. Neuropeptide-Y (NPY), relaxin-3 (RLN3), melanocortin 4 receptor (MC4R), and GnRH mRNA expression was 64%, 59%, 58%, 86% lower (P < 0.05), respectively, while gonadotropin inhibiting hormone (GnIH) and pro-opiomelanocortin (POMC) mRNA expression was 198% and 350% higher (P < 0.01) in the arcuate nucleus of LRFI steers. Expression of agouti-related protein (AGRP), relaxin/insulin-like family peptide receptor 1 (RXFP1), and melanocortin 3 receptor mRNA was similar between LRFI and HRFI animals. Pituitary expression of FSHβ (P < 0.03) and LHβ (P < 0.01) was correlated to hypothalamic GnRH levels suggesting that changes in gene expression within the arcuate nucleus had functional consequences. Leptin mRNA expression was 245% higher in the adipose tissue of LRFI steers consistent with lower levels of NPY and higher expression of POMC in their hypothalami. These data support the hypothesis that differences in hypothalamic neuropeptide gene expression underlie variation in feed

  17. Rats with a truncated ghrelin receptor (GHSR) do not respond to ghrelin, and show reduced intake of palatable, high-calorie food.

    Science.gov (United States)

    MacKay, Harry; Charbonneau, Valerie R; St-Onge, Veronique; Murray, Emma; Watts, Alexander; Wellman, Martin K; Abizaid, Alfonso

    2016-09-01

    Ghrelin, a peptide hormone produced by the stomach, is the endogenous ligand for the Growth Hormone Secretagogue Receptor (GHSR). Ghrelin acts on the GHSR to increase food intake, appetitive behaviors, and adiposity. Recently, a rat model with a null mutation to the GHSR gene (FHH-GHSR(m1/Mcwi)) was generated and used in behavioral studies, but the basic metabolic phenotype of this strain as well as that of the background strain (Fawn Hooded Hypertensive, FHH) has not been characterized in detail. Here we compared male FHH-GHSR(m1/Mcwi) rats with their wild-type littermates (FHH-WT) in a number of metabolic parameters. In the 24h of recovery following an acute overnight fast, FHH-GHSR(m1/Mcwi) rats consumed less food than FHH-WT animals, and relative to their body weights, adult FHH-GHSR(m1/Mcwi) rats consumed fewer calories when placed on a high-fat diet. Despite this, FHH-GHSR(m1/Mcwi) rats did not show a difference in diet-induced obesity or weight gain. Fasted FHH-GHSR(m1/Mcwi) rats exhibited increased Agouti-Related Peptide (AgRP) and Neuropeptide Y (NPY) expression in the Arcuate Nucleus (ARC), indicative of altered central regulation of feeding and energy balance. FHH-GHSR(m1/Mcwi) rats exhibited lower levels of home cage locomotor behavior over the entire light/dark cycle, and reduced levels of food anticipatory activity when placed on a restricted feeding schedule. Finally, FHH-GHSR(m1/Mcwi) rats consumed less of a palatable dessert (cookie dough) given after the completion of the scheduled meal. Altogether, our data show that rats lacking a functional GHSR tend to eat less than their wild-type counterparts in the face of acute fasts, chronic high-fat diet exposure, and exposure to a palatable dessert, despite not showing differences in body weight and glucose homeostasis that are characteristic of GHSR null mice. These data indicate that many, but not all responses to GHSR ablation are conserved between rats and mice. The FHH-GHSR(m1/Mcwi) rat thus

  18. Expression of Selenoprotein Genes Is Affected by Obesity of Pigs Fed a High-Fat Diet123

    Science.gov (United States)

    Zhao, Hua; Li, Ke; Tang, Jia-Yong; Zhou, Ji-Chang; Wang, Kang-Ning; Xia, Xin-Jie; Lei, Xin Gen

    2015-01-01

    Background: Relations of the 25 mammalian selenoprotein genes with obesity and the associated inflammation remain unclear. Objective: This study explored impacts of high-fat diet-induced obesity on inflammation and expressions of selenoprotein and obesity-related genes in 10 tissues of pigs. Methods: Plasma and 10 tissues were collected from pigs (n = 10) fed a corn-soy–based control diet or that diet containing 3–7% lard from weanling to finishing (180 d). Plasma concentrations (n = 8) of cytokines and thyroid hormones and tissue mRNA abundance (n = 4) of 25 selenoprotein genes and 16 obesity-related genes were compared between the pigs fed the control and high-fat diets. Stepwise regression was applied to analyze correlations among all these measures, including the previously reported body physical and plasma biochemical variables. Results: The high-fat diet elevated (P < 0.05) plasma concentrations of tumor necrosis factor α, interleukin-6, leptin, and leptin receptor by 29–42% and affected (P < 0.05–0.1) tissue mRNA levels of the selenoprotein and obesity-related genes in 3 patterns. Specifically, the high-fat diet up-regulated 12 selenoprotein genes in 6 tissues, down-regulated 13 selenoprotein genes in 7 tissues, and exerted no effect on 5 genes in any tissue. Body weights and plasma triglyceride concentrations of pigs showed the strongest regressions to tissue mRNA abundances of selenoprotein and obesity-related genes. Among the selenoprotein genes, selenoprotein V and I were ranked as the strongest independent variables for the regression of phenotypic and plasma measures. Meanwhile, agouti signaling protein, adiponectin, and resistin genes represented the strongest independent variables of the obesity-related genes for the regression of tissue selenoprotein mRNA. Conclusions: The high-fat diet induced inflammation in pigs and affected their gene expression of selenoproteins associated with thioredoxin and oxidoreductase systems, local tissue

  19. Transcriptional evidence for the role of chronic venlafaxine treatment in neurotrophic signaling and neuroplasticity including also Glutamatergic [corrected] - and insulin-mediated neuronal processes.

    Directory of Open Access Journals (Sweden)

    Viola Tamási

    Full Text Available Venlafaxine (VLX, a serotonine-noradrenaline reuptake inhibitor, is one of the most commonly used antidepressant drugs in clinical practice for the treatment of major depressive disorder (MDD. Despite being more potent than its predecessors, similarly to them, the therapeutical effect of VLX is visible only 3-4 weeks after the beginning of treatment. Furthermore, recent papers show that antidepressants, including also VLX, enhance the motor recovery after stroke even in non depressed persons. In the present, transcriptomic-based study we looked for changes in gene expressions after a long-term VLX administration.Osmotic minipumps were implanted subcutaneously into Dark Agouti rats providing a continuous (40 mg/kg/day VLX delivery for three weeks. Frontal regions of the cerebral cortex were isolated and analyzed using Illumina bead arrays to detect genes showing significant chances in expression. Gene set enrichment analysis was performed to identify specific regulatory networks significantly affected by long term VLX treatment.Chronic VLX administration may have an effect on neurotransmitter release via the regulation of genes involved in vesicular exocytosis and receptor endocytosis (such as Kif proteins, Myo5a, Sv2b, Syn2 or Synj2. Simultaneously, VLX activated the expression of genes involved in neurotrophic signaling (Ntrk2, Ntrk3, glutamatergic transmission (Gria3, Grin2b and Grin2a, neuroplasticity (Camk2g/b, Cd47, synaptogenesis (Epha5a, Gad2 and cognitive processes (Clstn2. Interestingly, VLX increased the expression of genes involved in mitochondrial antioxidant activity (Bcl2 and Prdx1. Additionally, VLX administration also modulated genes related to insulin signaling pathway (Negr1, Ppp3r1, Slc2a4 and Enpp1, a mechanism that has recently been linked to neuroprotection, learning and memory.Our results strongly suggest that chronic VLX treatment improves functional reorganization and brain plasticity by influencing gene expression in

  20. Engineering agatoxin, a cystine-knot peptide from spider venom, as a molecular probe for in vivo tumor imaging.

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    Sarah J Moore

    Full Text Available BACKGROUND: Cystine-knot miniproteins, also known as knottins, have shown great potential as molecular scaffolds for the development of targeted therapeutics and diagnostic agents. For this purpose, previous protein engineering efforts have focused on knottins based on the Ecballium elaterium trypsin inhibitor (EETI from squash seeds, the Agouti-related protein (AgRP neuropeptide from mammals, or the Kalata B1 uterotonic peptide from plants. Here, we demonstrate that Agatoxin (AgTx, an ion channel inhibitor found in spider venom, can be used as a molecular scaffold to engineer knottins that bind with high-affinity to a tumor-associated integrin receptor. METHODOLOGY/PRINCIPAL FINDINGS: We used a rational loop-grafting approach to engineer AgTx variants that bound to αvβ3 integrin with affinities in the low nM range. We showed that a disulfide-constrained loop from AgRP, a structurally-related knottin, can be substituted into AgTx to confer its high affinity binding properties. In parallel, we identified amino acid mutations required for efficient in vitro folding of engineered integrin-binding AgTx variants. Molecular imaging was used to evaluate in vivo tumor targeting and biodistribution of an engineered AgTx knottin compared to integrin-binding knottins based on AgRP and EETI. Knottin peptides were chemically synthesized and conjugated to a near-infrared fluorescent dye. Integrin-binding AgTx, AgRP, and EETI knottins all generated high tumor imaging contrast in U87MG glioblastoma xenograft models. Interestingly, EETI-based knottins generated significantly lower non-specific kidney imaging signals compared to AgTx and AgRP-based knottins. CONCLUSIONS/SIGNIFICANCE: In this study, we demonstrate that AgTx, a knottin from spider venom, can be engineered to bind with high affinity to a tumor-associated receptor target. This work validates AgTx as a viable molecular scaffold for protein engineering, and further demonstrates the promise of using

  1. Missense and nonsense mutations in melanocortin 1 receptor (MC1R gene of different goat breeds: association with red and black coat colour phenotypes but with unexpected evidences

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    Davoli Roberta

    2009-08-01

    Full Text Available Abstract Background Agouti and Extension loci control the relative amount of eumelanin and pheomelanin production in melanocytes that, in turn, affects pigmentation of skin and hair. The Extension locus encodes the melanocortin 1 receptor (MC1R whose permanent activation, caused by functional mutations, results in black coat colour, whereas other inactivating mutations cause red coat colour in different mammals. Results The whole coding region of the MC1R gene was sequenced in goats of six different breeds showing different coat colours (Girgentana, white cream with usually small red spots in the face; Maltese, white with black cheeks and ears; Derivata di Siria, solid red; Murciano-Granadina, solid black or solid brown; Camosciata delle Alpi, brown with black stripes; Saanen, white; F1 goats and the parental animals. Five single nucleotide polymorphisms (SNPs were identified: one nonsense mutation (p.Q225X, three missense mutations (p.A81V, p.F250V, and p.C267W, and one silent mutation. The stop codon at position 225 should cause the production of a shorter MC1R protein whose functionality may be altered. These SNPs were investigated in a larger sample of animals belonging to the six breeds. The Girgentana breed was almost fixed for the p.225X allele. However, there was not complete association between the presence of red spots in the face and the presence of this allele in homozygous condition. The same allele was identified in the Derivata di Siria breed. However, its frequency was only 33%, despite the fact that these animals are completely red. The p.267W allele was present in all Murciano-Granadina black goats, whereas it was never identified in the brown ones. Moreover, the same substitution was present in almost all Maltese goats providing evidence of association between this mutation and black coat colour. Conclusion According to the results obtained in the investigated goat breeds, MC1R mutations may determine eumelanic and pheomelanic

  2. MC1R and the response of melanocytes to ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rouzaud, Francois [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States); Kadekaro, Ana Luisa [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Abdel-Malek, Zalfa A. [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Hearing, Vincent J. [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States)]. E-mail: hearingv@nih.gov

    2005-04-01

    The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists {alpha}-melanocyte-stimulating hormone ({alpha}MSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of {alpha}MSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is

  3. Supplementation of branched-chain amino acids to a reduced-protein diet improves growth performance in piglets: involvement of increased feed intake and direct muscle growth-promoting effect.

    Science.gov (United States)

    Zheng, Liufeng; Wei, Hongkui; Cheng, Chuanshang; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

    2016-06-01

    The aim of this study was to investigate whether supplementing branched-chain amino acids (AA) (BCAA) along with a reduced-protein diet increases piglet growth, and whether elevated feed intake and muscle growth-promoting effect contribute to this improvement. In Expt 1, twenty-eight weanling piglets were randomly fed one of the following four diets: a positive control (PC) diet, a reduced-protein negative control (NC) diet, an NC diet supplemented with BCAA to the same levels as in the PC diet (test 1 (T1)) and an NC diet supplemented with a 2-fold dose of BCAA in T1 diet (test 2 (T2)) for 28 d. In Expt 2, twenty-one weanling piglets were randomly assigned to NC, T1 and pair-fed T1 (P) groups. NC and T1 diets were the same as in Expt 1, whereas piglets in the P group were individually pair-fed with the NC group. In Expt 1, the NC group had reduced piglet growth and feed intake compared with the PC group, which were restored in T1 and T2 groups, but no differences were detected between T1 and T2 groups. In Expt 2, T1 and P groups showed increases in growth and mass of some muscles compared with the NC group. Increased feed intake after BCAA supplementation was associated with increased mRNA expressions of agouti-related peptide and co-express neuropeptide Y (NPY) and phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase 1 (S6K1), as well as decreased mRNA expressions of melanocortin-4 receptor and cocaine- and amphetamine-regulated transcript and phosphorylation of eukaryotic initiation factor 2α in the hypothalamus. No differences were observed among PC, T1 and T2 groups except for higher NPY mRNA expression in the T2 group than in the PC group (Expt 1). Phosphorylation of mTOR and S6K1 in muscle was enhanced after BCAA supplementation, which was independent of change in feed intake (Expt 2). In conclusion, supplementing BCAA to reduced-protein diets increases feed intake and muscle mass, and contributes to better growth

  4. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

    2016-04-01

    Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lowerPomcbut higherAgrpmRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic lateral

  5. Anorexia is Associated with Stress-Dependent Orexigenic Responses to Exogenous Neuropeptide Y.

    Science.gov (United States)

    Yi, J; Delp, M S; Gilbert, E R; Siegel, P B; Cline, M A

    2016-05-01

    Chicken lines that have been divergently selected for either low (LWS) or high (HWS) body weight at 56 days of age for more than 57 generations have different feeding behaviours in response to a range of i.c.v. injected neurotransmitters. The LWS have different severities of anorexia, whereas the HWS become obese. Previously, we demonstrated that LWS chicks did not respond, whereas HWS chicks increased food intake, after central injection of neuropeptide Y (NPY). The present study aimed to determine the molecular mechanisms underlying the loss of orexigenic function of NPY in LWS. Chicks were divided into four groups: stressed LWS and HWS on day of hatch, and control LWS and HWS. The stressor was a combination of food deprivation and cold exposure. On day 5 post-hatch, each chick received an i.c.v. injection of vehicle or 0.2 nmol of NPY. Only the LWS stressed group did not increase food intake in response to i.c.v. NPY. Hypothalamic mRNA abundance of appetite-associated factors was measured at 1 h post-injection. Interactions of genetic line, stress and NPY treatment were observed for the mRNA abundance of agouti-related peptide (AgRP) and synaptotagmin 1 (SYT1). Intracerebroventricular injection of NPY decreased and increased AgRP and SYT1 mRNA, respectively, in the stressed LWS and increased AgRP mRNA in stressed HWS chicks. Stress was associated with increased NPY, orexin receptor 2, corticotrophin-releasing factor receptor 1, melanocortin receptor 3 (MC3R) and growth hormone secretagogue receptor expression. In conclusion, the loss of responsiveness to exogenous NPY in stressed LWS chicks may be a result of the decreased and increased hypothalamic expression of AgRP and MC3R, respectively. This may induce an intensification of anorexigenic melanocortin signalling pathways in LWS chicks that block the orexigenic effect of exogenous NPY. These results provide insights onto the anorexic condition across species, and especially for forms of inducible anorexia

  6. MC1R and the response of melanocytes to ultraviolet radiation

    International Nuclear Information System (INIS)

    The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists α-melanocyte-stimulating hormone (αMSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of αMSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is considered a

  7. Novel role for SLPI in MOG-induced EAE revealed by spinal cord expression analysis

    Directory of Open Access Journals (Sweden)

    Aigner Ludwig

    2008-05-01

    Full Text Available Abstract Background Experimental autoimmune encephalomyelitis (EAE induced by myelin oligodendrocyte protein (MOG in female Dark Agouti (DA rats is a chronic demyelinating animal model of multiple sclerosis (MS. To identify new candidate molecules involved in the evolution or repair of EAE-lesions we used Affymetrix oligonucleotide microarrays to compare the spinal cord transcriptome at the peak of EAE, during remission and at the first relapse with healthy DA rats. Methods Untreated DA rats and DA rats immunised with MOG protein were sacrificed at defined time points. Total RNA was isolated from spinal cord tissue and used for hybridization of Affymetrix rat genome arrays RG U34 A-C. Selected expression values were confirmed by RealTime PCR. Adult neural stem cells were incubated with recombinant secretory leukocyte protease inhibitor (SLPI. Proliferation was assessed by BrdU incorporation, cyclin D1 and HES1 expression by RealTime PCR, cell differentiation by immunofluorescence analysis and IkappaBalpha degradation by Western blot. Results Among approximately 26,000 transcripts studied more than 1,100 were differentially regulated. Focussing on functional themes, we noticed a sustained downregulation of most of the transcripts of the cholesterol biosynthesis pathway. Furthermore, we found new candidate genes possibly contributing to regenerative processes in the spinal cord. Twelve transcripts were solely upregulated in the recovery phase, including genes not previously associated with repair processes. Expression of SLPI was upregulated more than hundredfold during EAE attack. Using immunohistochemistry, SLPI was identified in macrophages, activated microglia, neuronal cells and astrocytes. Incubation of adult neural stem cells (NSC with recombinant SLPI resulted in an increase of cell proliferation and of differentiation towards oligodendrocytes. These processes were paralleled by an upregulation of the cell-cycle promotor cyclin D1 and a

  8. A composite six bp in-frame deletion in the melanocortin 1 receptor (MC1R gene is associated with the Japanese brindling coat colour in rabbits (Oryctolagus cuniculus

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    Russo Vincenzo

    2010-07-01

    Full Text Available Abstract Background In the domestic rabbit (Oryctolagus cuniculus, classical genetic studies have identified five alleles at the Extension locus: ED (dominant black, ES (steel, weaker version of ED, E (wild type, normal extension of black, eJ(Japanese brindling, mosaic distribution of black and yellow and e (non-extension of black, yellow/red with white belly. Sequencing almost the complete coding sequence (CDS of the rabbit MC1R gene, we recently identified two in-frame deletions associated with dominant black (c.280_285del6; alleles ED or ES and recessive red (c.304_333del30; allele e coat colours. It remained to characterize the eJallele whose phenotypic effect is similar to the Orange and Sex-linked yellow loci of cat and Syrian hamster. Results We sequenced the whole CDS in 25 rabbits of different coat colours including 10 Japanese and 10 Rhinelander (tricolour rabbits and identified another 6 bp-in frame deletion flanked by a G > A transition in 5' (c.[124G>A;125_130del6] that was present in all animals with Japanese brindling coat colour and pattern. These mutations eliminate two amino acids in the first transmembrane domain and, in addition, cause an amino acid substitution at position 44 of the wild type sequence. Genotyping 371 rabbits of 31 breeds with different coat colour this allele (eJ was present in homozygous state in Japanese, Rhinelander and Dutch tricolour rabbits only (except one albino rabbit. Rabbits with eJ/eJ genotype were non fixed at the non-agouti mutation we previously identified in the ASIP gene. Segregation in F1 and F2 families confirmed the order of dominance already determined by classical genetic experiments with a possible dose effect evident comparing eJ/eJ and eJ/e animals. MC1R mRNA was expressed in black hair skin regions only. Conclusions The c.[124A;125_130del6] allele may be responsible for a MC1R variant determining eumelanin production in the black areas. However, the mechanism determining the

  9. Sestamibi is a substrate for MDR1 and MDR2 P-glycoprotein genes

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, Brigid; Malhi, Harmeet; Gupta, Sanjeev [Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Ullmann 625, 1300 Morris Park Avenue, NY 10461, Bronx (United States); Bhargava, Kuldeep K.; Palestro, Christopher J. [Division of Nuclear Medicine, Long Island Jewish Medical Center, New York (United States); Schilsky, Michael L. [Division of Liver Diseases, Mount Sinai School of Medicine, New York (United States); Jain, Diwakar [Division of Nuclear Cardiology, MCP-Hahnemann University School of Medicine, Philadephia (United States)

    2003-07-01

    Technetium-99m sestamibi has attracted interest for assessment of the function of P-glycoproteins, which are well expressed in the liver and have roles in biliary transport and the removal of chemotherapeutic drugs. To further examine the cross-reactivity of {sup 99m}Tc-sestamibi for P-glycoprotein family members, we conducted studies in animals. Hepatobiliary secretion of {sup 99m}Tc-sestamibi was determined in normal FVB/N mice, mutant mice with specific P-glycoprotein deficiencies in the FVB/N background, normal Long-Evans Agouti (LEA) rats, and Long-Evans Cinnamon (LEC) rats with abnormal copper transport and liver disease but intact P-glycoprotein expression. After intrasplenic injection, {sup 99m}Tc-sestamibi was rapidly incorporated in the mouse and rat liver, with maximal accumulation after 102{+-}31 and 109{+-}16 s, respectively (P=NS). In normal mice and rats, 55%{+-}11% and 55%{+-}6%, respectively, of the maximal sestamibi activity was retained in the liver after 1 h (P=NS). In double knockout mice lacking both mdr1a and mdr1b homologs of the human MDR1 (ABCB1) gene, 88%{+-}11% of maximal sestamibi activity was retained in the liver after 1 h (P<0.001). In knockout mice deficient in either mdr1a gene or mdr2 (ABCB4) gene, biliary sestamibi excretion was also impaired, although this impairment was relatively less pronounced in ABCB4-deficient mice than in double knockout mice lacking both ABCB1 gene homologs (P<0.03). Hepatobiliary sestamibi excretion in LEC rats was not different from that in control normal rats, despite the presence of significant liver disease in the former. Hepatobiliary sestamibi excretion requires P-glycoproteins and is unperturbed in chronic liver disease. Sestamibi appears to be a substrate for both ABCB1 and ABCB4 genes, although the former utilizes it far more efficiently. Assessment of P-glycoprotein activity with sestamibi should consider how regulation of ABCB1 and related family members might modulate sestamibi incorporation

  10. Betulinic acid regulates generation of neuroinflammatory mediators responsible for tissue destruction in multiple sclerosis in vitro

    Institute of Scientific and Technical Information of China (English)

    Jana BLA(Z)EVSKI; Filip PETKOVI(C); Miljana MOM(C)ILOVI(C); Reinhard PASCHKE; Goran N KALUDEROVI(C); Marija MOSTARICA STOJKOVI(C); Djordje MILJKOVI(C)

    2013-01-01

    Aim:To investigate the influences of betulinic acid (BA),a triterpenoid isolated from birch bark,on neuroinflammatory mediators involved in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis in vitro.Methods:Encephalitogenic T cells were prepared from draining lymph nodes and spinal cords of Dark Agouti rats 8 to 10 d after immunization with myelin basic protein (MBP) and complete Freund's adjuvant.Macrophages were isolated from the peritoneal cavity of adult untreated rats.Astrocytes were isolated from neonatal rat brains.The cells were cultured and then treated with different agents.IFN-y,IL-17,iNOS and CXCL12 mRNA levels in the cells were analyzed with RT-PCR.iNOS and CXCL12 protein levels were detected using immunoblot.NO and ROS generation was measured using Griess reaction and flow cytometry,respectively.Results:In encephalitogenic T cells stimulated with MBP (10 μg/mL),addition of BA inhibited IL-17 and IFN-γ production in a dosedependent manner.The estimated IC50 values for IL-17 and IFN y were 11.2 and 63.8 μmol/L,respectively.When the macrophages were stimulated with LPS (10 ng/mL),addition of BA (50 μmol/L) significantly increased ROS generation,and suppressed NO generation.The astrocytes were stimulated with ConASn containing numerous inflammatory mediators,which mimicked the inflammatory milieu within CNS; addition of BA (50 μmol/L) significantly increased ROS generation,and blocked ConASn-induced increases in iNOS and CXCL12 mRNA levels,but did not affect iNOS and CXCL12 protein levels.Importantly,in both the macrophages and astrocytes,addition of BA (50 μmol/L) inhibited lipid peroxidation.Conclusion:Besides inhibiting encephalitogenic T cell cytokines and reducing NO generation,BA induces tissue-damaging ROS generation within CNS.

  11. Computational Analysis of the Hypothalamic Control of Food Intake.

    Science.gov (United States)

    Tabe-Bordbar, Shayan; Anastasio, Thomas J

    2016-01-01

    Food-intake control is mediated by a heterogeneous network of different neural subtypes, distributed over various hypothalamic nuclei and other brain structures, in which each subtype can release more than one neurotransmitter or neurohormone. The complexity of the interactions of these subtypes poses a challenge to understanding their specific contributions to food-intake control, and apparent consistencies in the dataset can be contradicted by new findings. For example, the growing consensus that arcuate nucleus neurons expressing Agouti-related peptide (AgRP neurons) promote feeding, while those expressing pro-opiomelanocortin (POMC neurons) suppress feeding, is contradicted by findings that low AgRP neuron activity and high POMC neuron activity can be associated with high levels of food intake. Similarly, the growing consensus that GABAergic neurons in the lateral hypothalamus suppress feeding is contradicted by findings suggesting the opposite. Yet the complexity of the food-intake control network admits many different network behaviors. It is possible that anomalous associations between the responses of certain neural subtypes and feeding are actually consistent with known interactions, but their effect on feeding depends on the responses of the other neural subtypes in the network. We explored this possibility through computational analysis. We made a computer model of the interactions between the hypothalamic and other neural subtypes known to be involved in food-intake control, and optimized its parameters so that model behavior matched observed behavior over an extensive test battery. We then used specialized computational techniques to search the entire model state space, where each state represents a different configuration of the responses of the units (model neural subtypes) in the network. We found that the anomalous associations between the responses of certain hypothalamic neural subtypes and feeding are actually consistent with the known structure

  12. Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons.

    Directory of Open Access Journals (Sweden)

    Sangdeuk Ha

    Full Text Available Leptin acts via neuronal leptin receptors to control energy balance. Hypothalamic pro-opiomelanocortin (POMC and agouti-related peptide (AgRP/Neuropeptide Y (NPY/GABA neurons produce anorexigenic and orexigenic neuropeptides and neurotransmitters, and express the long signaling form of the leptin receptor (LepRb. Despite progress in the understanding of LepRb signaling and function, the sub-cellular localization of LepRb in target neurons has not been determined, primarily due to lack of sensitive anti-LepRb antibodies. Here we applied light microscopy (LM, confocal-laser scanning microscopy (CLSM, and electron microscopy (EM to investigate LepRb localization and signaling in mice expressing a HA-tagged LepRb selectively in POMC or AgRP/NPY/GABA neurons. We report that LepRb receptors exhibit a somato-dendritic expression pattern. We further show that LepRb activates STAT3 phosphorylation in neuronal fibers within several hypothalamic and hindbrain nuclei of wild-type mice and rats, and specifically in dendrites of arcuate POMC and AgRP/NPY/GABA neurons of Leprb (+/+ mice and in Leprb (db/db mice expressing HA-LepRb in a neuron specific manner. We did not find evidence of LepRb localization or STAT3-signaling in axon-fibers or nerve-terminals of POMC and AgRP/NPY/GABA neurons. Three-dimensional serial EM-reconstruction of dendritic segments from POMC and AgRP/NPY/GABA neurons indicates a high density of shaft synapses. In addition, we found that the leptin activates STAT3 signaling in proximity to synapses on POMC and AgRP/NPY/GABA dendritic shafts. Taken together, these data suggest that the signaling-form of the leptin receptor exhibits a somato-dendritic expression pattern in POMC and AgRP/NPY/GABA neurons. Dendritic LepRb signaling may therefore play an important role in leptin's central effects on energy balance, possibly through modulation of synaptic activity via post-synaptic mechanisms.

  13. Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

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    Yuta Abe

    Full Text Available BACKGROUND: Donor-specific blood transfusion (DST prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported. Therefore, the objective of this study was to define the kinetics, phenotype and suppressive function of the regulatory cells induced by DST alone or in combination with liver allograft transplantation (LTx. METHODOLOGY/PRINCIPAL FINDINGS: Tolerance to Dark Agouti (DA; RT1(a rat liver allografts was induced by injection (iv of 1 ml of heparinized DA blood to naïve Lewis (LEW; RT1(l rats once per week for 4 weeks prior to LTx. We found that preoperative DST alone generates CD4(+ T-cells that when transferred into naïve LEW recipients are capable of suppressing DA liver allograft rejection and promoting long-term survival of the graft and recipient. However, these DST-generated T-cells did not express the regulatory T-cell (Treg transcription factor Foxp3 nor did they suppress alloantigen (DA-induced activation of LEW T-cells in vitro suggesting that these lymphocytes are not fully functional regulatory Tregs. We did observe that DST+LTx (but not DST alone induced the time-dependent formation of CD4(+Foxp3(+ Tregs that potently suppressed alloantigen-induced activation of naïve LEW T-cells in vitro and liver allograft rejection in vivo. Finally, we present data demonstrating that virtually all of the Foxp3-expressing Tregs reside within the CD4(+CD45RC(- population whereas in which approximately 50% of these Tregs express CD25. CONCLUSIONS/SIGNIFICANCE: We conclude that preoperative DST, in the absence of liver allograft

  14. Evidence suggesting phosphodiesterase-3B regulation of NPY/AgRP gene expression in mHypoE-46 hypothalamic neurons.

    Science.gov (United States)

    Anamthathmakula, Prashanth; Sahu, Maitrayee; Sahu, Abhiram

    2015-09-14

    Hypothalamic neurons expressing neuropeptide Y (NPY) and agouti related-protein (AgRP) are critical regulators of feeding behavior and body weight, and transduce the action of many peripheral signals including leptin and insulin. However, intracellular signaling molecules involved in regulating NPY/AgRP neuronal activity are incompletely understood. Since phosphodiesterase-3B (PDE3B) mediates the hypothalamic action of leptin and insulin on feeding, and is expressed in NPY/AgRP neurons, PDE3B could play a significant role in regulating NPY/AgRP neuronal activity. To investigate the direct regulation of NPY/AgRP neuronal activity by PDE3B, we examined the effects of gain-of-function or reduced function of PDE3B on NPY/AgRP gene expression in a clonal hypothalamic neuronal cell line, mHypoE-46, which endogenously express NPY, AgRP and PDE3B. Overexpression of PDE3B in mHypoE-46 cells with transfection of pcDNA-3.1-PDE3B expression plasmid significantly decreased NPY and AgRP mRNA levels and p-CREB levels as compared to the control plasmid. For the PDE3B knockdown study, mHypoE-46 cells transfected with lentiviral PDE3BshRNAmir plasmid or non-silencing lentiviral shRNAmir control plasmid were selected with puromycin, and stably transfected cells were grown in culture for 48h. Results showed that PDE3BshRNAmir mediated knockdown of PDE3B mRNA and protein levels (∼60-70%) caused an increase in both NPY and AgRP gene expression and in p-CREB levels. Together, these results demonstrate a reciprocal change in NPY and AgRP gene expression following overexpression and knockdown of PDE3B, and suggest a significant role for PDE3B in the regulation of NPY/AgRP gene expression in mHypoE-46 hypothalamic neurons.

  15. 大鼠腹腔内心脏移植模型的构建和体会%Experiences of establishing an abdominal heart transplantation model in rats

    Institute of Scientific and Technical Information of China (English)

    陈浩; 梅运清; Michael A Solomon

    2012-01-01

    Objective To review the experiences and key factors of establishing an abdominal cardiac transplantation model in rats at National Institutes of Health Clinical Center.Methods Dark Agouti rats served as donor while Brown Norway rats as recipient.Cardiac transplantations were performed with a modified version of heterotopic cardiac transplantation.Proficiency was defined as 20 consecutive operations with < 15% mortality and no significant major co-morbidities.Results We performed 10 donor harvestalone operations and 70 transplantations to reach the proficiency level The survival rate of the last 20 consecutive surgeries was 95%.The mean total operative duration was 55 ruin and mean ischemic time of donor hearts 35 min.Conclusion To ensure a consistently high operative success rate,a surgeon must not only be proficient in micro-surgical skills,but also closely follow the standardized training procedures and strictly observe the animal care and use guidelines.%目的 总结在美国国立卫生研究院临床中心建立大鼠腹腔内心脏移植模型的经验,探讨手术成功的主要影响因素.方法 以80只Dark Agouti大鼠为供体,70只Brown Norway大鼠为受体,制作大鼠心脏移植模型.以连续20例手术死亡率低于15%且无明显合并症为手术合格标准.结果 为达到合格标准,共施行了10例大鼠供体手术,70例大鼠移植手术.最后20例移植手术成功率为95%,平均手术时间为55 min,供心平均缺血时间为35 min.结论 精准的显微外科技术,加上标准化手术训练和严格的动物管理,是保证手术成功率的关键因素.

  16. - Un modelo descriptivo del sistema reproductor hembra del coipo (Myocastor coypus I: el ovario (A descriptive model of the female reproductive system of coypu (Myocastor coypus I: the ovary

    Directory of Open Access Journals (Sweden)

    Felipe, A. E.

    2005-12-01

    conformada por tejido conectivo en disposición plexiforme, en el cual las fibras se orientaron en todas direcciones. Se observaron también fibras elásticas y argentófilas. En los ejemplares estudiados fue posible identificar todos los tipos foliculares y determinar la presencia de distintos grados de atresia correspondientes a folículos en diferentes etapas de desarrollo. Los folículos en crecimiento (secundarios atrésicos se caracterizaron por el engrosamiento de la zona pelúcida, la vacuolización citoplasmática de células foliculares, picnosis, vacuolización de la teca interna y tejido conectivo de sustitución. Con respecto a las estructuras consideradas como cuerpos lúteos, pudieron establecerse y caracterizarse tres grados de desarrollo de los mismos (inicial, medio y maduro así como determinarse diferentes estadíos de regresión o atresia. Todos los ovarios del coipo contuvieron cuerpos lúteos accesorios. Los mismos se diferenciaron de los verdaderos por su menor tamaño y la persistencia de un remanente ovocitario con una zona pelúcida degenerada. El diámetro medio de estas estructuras fue de 273.44 ± 78.22 mm. Las observaciones presentadas en este trabajo indican que el ovario de coipos sexualmente maduros es semejante al de otros mamíferos como la chinchilla (Chinchilla laniger, el cobayo (Cavia sp., la casiragua (Proechimys guairae, el carpincho (Hydrochoerus hydrochaeris, la mara (Dolichotis patagonum, el aguti (Dasyprocta aguti, el puercoespín africano austral (Hystrix africaeaustralis y el puercoespín africano común (Atherurus africanus. In the present investigation mature females of coypu (Myocastor coypus were used to determine the anatomic and histomorphologic features of the ovaries. As in all mammals, the ovary was suspended from the dorsal wall of the peritoneal cavity by the mesovarium. In the studied animals, the mesovarium did not form a bursa. The ovary of the coypu is similar to the ovary of other adult hystricomorph rodents: it

  17. Combate ao Desmodus rotundus rotundus (E. Geoffroy,1810 na região cárstica de Cordisburgo e Curvelo, Minas Gerais

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    Almeida E.O.

    2002-01-01

    Full Text Available Com o objetivo de avaliar em uma região cárstica o tipo de refúgio, as espécies de morcegos, a população de animais domésticos, as associações interespecíficas nas coabitações com outros mamíferos silvestres suscetíveis à raiva e a eficácia da warfarina aplicada no dorso do Desmodus rotundus rotundus foi realizada uma pesquisa de maio de 1998 a março de 2000, nos municípios de Cordisburgo e Curvelo, Minas Gerais. Em 49 refúgios vistoriados, 29 naturais e 20 artificiais, localizados em 14 propriedades, encontrou-se o Desmodus rotundus rotundus em 18 abrigos naturais. Destes, 17 eram cavernas formadas pela dissolução ou abatimento de rocha calcária, típica do carste, e um era túnel escavado na terra pela ação das águas de um rio. As características geomorfológicas e de localização espacial foram registradas com base nas coordenadas geográficas, obtidas com auxílio de um sensor geográfico de posição. Nesses abrigos foram capturados e identificados 1457 morcegos de 14 espécies, sendo 640 Glossophaga soricina (Pallas, 1766, 566 Desmodus rotundus (E. Geoffroy, 1810, 73 Anoura geoffroyi (Gray 1838, 58 Trachops cirrhosus (Spix, 1823, 38 Diphylla ecaudata ecaudata (Spix, 1823, 23 Platyhrrinus lineatus (E. Geoffroy, 1810, 16 Lasiurus ega (Gervais, 1856, 14 Carollia perspicillata (Linnaeus, 1758, 13 Phyllostomus hastatus hastatus (Pallas, 1767, 9 Artibeus lituratus (Olfers, 1818, 3 Mimmon bennettii (Gray, 1838, 2 Myotis nigricans (Schinz, 1821, 1 Eptesicus brasiliensis (Desmarest, 1819 e 1 Pygoderma bilabiatum (Wagner, 1843. Não se conseguiu isolar ou detectar o vírus rábico no cérebro de 25 hematófagos selecionados e em 52 de outras espécies. A maioria desses abrigos também era usada por pacas (Agouti paca Linnaues, 1766, capivaras (Hydrochaeris hydrochaeris, Linnaues, 1766, guaxinins (Procyon cancrivorus, G. Cuvier, 1798 e raposas (Lycalopex vetulus, Lund, 1842 que são suscetíveis à raiva. Em 546 Desmodus

  18. 大鼠内细胞团和胎儿神经干细胞构建嵌合体的潜力%The Potential of Rat Inner Cell Mass and Fetal Neural Stem Cells to Generate Chimeras

    Institute of Scientific and Technical Information of China (English)

    郭继彤; 李雪峰; Shahnaz Fida; 苟克勉; Nakisa Malakooti; ZHANG Chun-fang; John R Morrison; Alan O Trounson; DU Zhong-tao

    2009-01-01

    嵌合体大鼠是研究人类疾病的重要动物模犁.用囊胚注射法研究了大鼠内细胞团(ICM)和胎儿神经干细胞(FNS)构建嵌合体的潜力.结果发现来自黑色(DA)大鼠第5天(D5)和第6天(D6)囊胚的ICM细胞注入D5 Sprague-Dawley(SD)大鼠囊胚后得到3只嵌合体大鼠:D5 SD大鼠ICM细胞注射入D5 DA囊胚后得到4只嵌合体大鼠:而体外培养的DA或SD人鼠ICM细胞注射后均未能获得嵌合体大鼠.本研究用大鼠胎儿神经干细胞(rFNS)和LacZ转染的rFNS构建嵌介体,未能获得嵌合体人鼠:但在LacZ转染的SD rFNS注射到DA大鼠囊胚后发育来的41只胎儿中,有2只胎儿其组织切片中发现少量LacZ阳性细胞.结果表明DA和SD大鼠ICM具有参与嵌合体发育的潜力,但ICM细胞经体外培养后构建嵌合体的潜力显著F降(P<0.05);大鼠胎儿神经干细胞构建嵌合体的潜力较低,可能仅具有参与早期胚胎发育的潜力.%The rat chimera is an important animal model for the study of complex human diseases. In the present study we evaluated the chimeric potential of rat inner cell masses (ICMs) and fetal neural stem (FNS) cells. In result, three rat chimeras were produced by day 5 (D5) Sprague-Dawley (SD) blastocysts injected with ICMs derived from day 6 (D6) and D5 Dark Agouti (DA) blastocysts; four rat chimeras had been generated by D5 DA blastocyst injected with D5 SD ICMs. For the requirement of gene modification, cultured rat inner cell mass cells were assessed to produce chimeras, but no chimeras were generated from injected embryos. The potential to generate chimeras from rFNS and transfected rFNS cells were tested, but no chimeric pups were produced. Only 2 of 41 fetuses derived from D5 DA blastocyst injection with SD LacZ transfected rFNS cells showed very low number of LacZ positive cells in the section. These results indicate that DA and SD rat ICMs are able to contribute to chimeras, but their potential decreases significantly after

  19. A closer look at evolution: Variants (SNPs) of genes involved in skin pigmentation, including EXOC2, TYR, TYRP1, and DCT, are associated with 25(OH)D serum concentration.

    Science.gov (United States)

    Saternus, Roman; Pilz, Stefan; Gräber, Stefan; Kleber, Marcus; März, Winfried; Vogt, Thomas; Reichrath, Jörg

    2015-01-01

    Vitamin D deficiency is common in the Caucasian population and is associated with increased incidence and unfavorable outcome of many diseases, including various types of cancer, infectious, cardiovascular, and autoimmune diseases. Individual factors that predispose for a person's vitamin D status, such as skin type, have been identified, but limited data exist on genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration. We have tested the hypothesis that variants of genes (single nucleotide polymorphisms [SNPs]) involved in skin pigmentation are predictive of serum 25(OH)D levels. Serum 25(OH)D and SNPs (n = 960) related to genes with relevance for skin pigmentation (tyrosinase [TYR], TYR-related protein 1 [TYRP1], dopachrome tautomerase [DCT], oculocutaneous albinism II [OCA2], two pore segment channel 2 [TPCN2], solute carrier family 24 A4 [SLC24A4], solute carrier family 45 A2 [SLC45A2], agouti signalling peptide [ASIP], cyclic AMP-dependent transcription factor [ATF1], microphthalmia-associated transcription factor [MITF], proopiomelanocortin [POMC], cAMP-dependent protein kinase catalytic subunit beta [PRKACB], cAMP-dependent protein kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I-alpha regulatory subunit [PRKAR1A], cAMP-dependent protein kinase type II-alpha regulatory subunit [PRKAR2A], cAMP-dependent protein kinase type II-beta regulatory subunit [PRKAR2B], tubulin beta-3 chain/melanocortin receptor 1 [TUBB3/MC1R], Cadherin-1 [CDH1], catenin beta 1 [CTNNB1], Endothelin 1 [EDN1], endothelin 3 [EDN3], endothelin receptor type B [EDNRB], fibroblast growth factor 2 [FGF2], KIT, KIT ligand [KITLG], nerve growth factor [NGF], interferon regulatory factor 4 [IRF4], exocyst complex component 2 [EXOC2], and tumor protein 53 [TP53]) were analyzed in a cohort of participants of the Ludwigshafen Risk and Cardiovascular Health Study (n = 2970). A total of 46 SNPs were associated (P <.05) with lower or higher serum 25(OH

  20. Regulatory mechanisms of melanogenesis in human skin%人皮肤黑素生成调控机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    倪亚杰; 王平

    2012-01-01

    Melanin in human skin is synthesized in the melanosomes of melanocytes,and there are many modes of regulation of melanogenesis,such as transcriptional regulation,regulation by intracellular signaling pathway,feedback regulation by products,and other positive(stimulation)or negative(inhibitory)regulation by nuclear receptors and cytokines.During the process of melanogenesis,microphthalmia transcription factor(MITF)plays a fundamental role in the regulation of tyrosinases and other tyrosinase-related proteins,with cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)pathway,mitogen-activated protein kinase(MAPK)pathway,nitric oxide/cyclic guanosine monophosphate/protein kinase G(NO/cGMP/PKG)pathway and diacylglycerol/protein kinase C(DG/PKC)pathway as the four major intracellular signaling pathways.Some molecules and their receptors play positive(stimulating)roles in melanogenesis,such as G protein-coupled receptors and their ligands,stem cell growth factor and its receptor,nuclear receptors and their ligands,while some molecules and receptors play negative(inhibiting)roles,such as the Agouti signaling protein and its receptor,G protein-coupled receptors and their ligands,as well as cytokines,growth factors and their receptors.%人皮肤黑素在黑素细胞的黑素小体内合成,受多重因素的复杂调控,包括转录调节、细胞内信号传导通路调节、产物的反馈调节,以及核受体、细胞因子等对黑素生成的正向(刺激)和负向(抑制)调节.在正常黑素生成过程中,小眼畸形相关转录因子是转录调控酪氨酸酶及其相关蛋白的最重要分子;环磷酸腺苷/蛋白激酶A通路、丝裂原激活的蛋白激酶通路、一氧化氮/环磷酸鸟苷/蛋白激酶G通路、二酯酰甘油/蛋白激酶C通路是参与黑素生成的最主要4条细胞内信号传导通路.对黑素生成有正向(刺激)作用的分子及其受体主要有G蛋白耦联受体及其配体、干细胞生长

  1. Book Reviews

    Directory of Open Access Journals (Sweden)

    Redactie KITLV

    2001-07-01

    Full Text Available -Stanley L. Engerman, Heather Cateau ,Capitalism and slavery fifty years later: Eric Eustace Williams - A reassessment of the man and his work. New York: Peter Lang, 2000. xvii + 247 pp., S.H.H. Carrington (eds -Philip D. Morgan, B.W. Higman, Writing West Indian histories. London: Macmillan Caribbean, 1999. xiv + 289 pp. -Daniel Vickers, Alison Games, Migration and the origins of the English Atlantic world. Cambridge MA: Harvard University Press, 1999. xiii + 322 pp. -Christopher L. Brown, Andrew Jackson O'Shaughnessy, An empire divided: The American revolution and the British Caribbean. Philadelphia: University of Pennsylvania Press, 2000. xviii + 357 pp. -Lennox Honychurch, Samuel M. Wilson, The indigenous people of the Caribbean. Gainesville: University Press of Florida, 1997. xiv + 253 pp. -Kenneth Bilby, Bev Carey, The Maroon story: The authentic and original history of the Maroons in the history of Jamaica 1490-1880. St. Andrew, Jamaica: Agouti Press, 1997. xvi + 656 pp. -Bernard Moitt, Doris Y. Kadish, Slavery in the Caribbean Francophone world: Distant voices, forgotten acts, forged identities. Athens: University of Georgia Press, 2000. xxiii + 247 pp. -Michael J. Guasco, Virginia Bernhard, Slaves and slaveholders in Bermuda, 1616-1782. Columbia: University of Missouri Press, 1999. xviii + 316 pp. -Michael J. Jarvis, Roger C. Smith, The maritime heritage of the Cayman Islands. Gainesville: University Press of Florida, 2000. xxii + 230 pp. -Paul E. Hoffman, Peter R. Galvin, Patterns of pillage: A geography of Caribbean-based piracy in Spanish America, 1536-1718. New York: Peter Lang, 1999. xiv + 271 pp. -David M. Stark, Raúl Mayo Santana ,Cadenas de esclavitud...y de solidaridad: Esclavos y libertos en San Juan,siglo XIX. Río Piedras: Centro de Investigaciones Sociales, Universidad de Puerto Rico, 1997. 204 pp., Mariano Negrón Portillo, Manuel Mayo López (eds -Ada Ferrer, Philip A. Howard, Changing history: Afro-Cuban Cabildos and

  2. Influence of reference genes on expression of TYR, MITF and ASIP genes in tissues of Silky Fowl%内参基因对 TYR、MITF和ASIP基因在白绒乌骨鸡各组织表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    郑嫩珠; 李丽; 辛清武; 缪中纬; 朱志明; 刘凤辉; 吴俭飞; 卢立志

    2015-01-01

    that taking GA PD H as a reference gene , the expressionlevelof TYR,ASIPandMITFgeneswiththemelanincontentintissueshadthesametrend:skin >kidney > gizzard > liver > muscle , but the expression level of A SIP gene was opposite to melanin deposition content , which implied that each target gene expression was matched with their respective function on regulating melanin deposition . For instance , high expression of TYR and MITF genes promoted melanin deposition , while the ASIP gene inhibited melanin deposition . Taking 18S rRNA and ACTB as reference genes , the expression of TYR,MITFandASIPgeneswerenotrelatedtothemelanindeposition,andanidealcalibrationresultcouldnot be obtained . In conclusion , reference gene plays an important role in the expression of target gene . In this paper , GA PD H gene not only had highest expression stability in tissues , but also could truly reflect the regulation effect of the targetgenes(TYR,MITFandASIP) onmelanindeposition.Thus,GAPDHgeneisthemostsuitablereference gene for normalizing the mRNA expression of genes in tissues of Silky Fowl .%以健康白绒乌骨鸡肌肉、肾、肝、肌胃和皮肤为试验素材,应用实时荧光定量聚合酶链反应技术探讨β‐肌动蛋白(beta‐actin ,ACTB)、3‐磷酸甘油醛脱氢酶(glyceraldehyde‐3‐phosphate dehydrogenase ,GA PDH)和18S核糖体RNA(18S ribosomal RNA ,18S rRNA )3个内参基因的组织表达稳定性及其对酪氨酸酶( tyrosinase ,TYR)、小眼畸形相关转录因子(microphthalmia‐associated transcription factor ,MITF)和刺鼠信号蛋白(agouti signaling pro tein ,A S I P)等目的基因在白绒乌骨鸡各组织表达水平的影响,并采用紫外分光光度法分析各组织黑色素沉积规律,从中筛选出理想的内参基因.geNorm和NormFinder软件分析结果显示,内参基因GA PD H在白绒乌骨鸡各组织表达稳定性最高,ACTB表达稳定性最低.相对定量和黑色素沉积结果表明,GA PDH作为内参基因时,各组织 MITF

  3. Desnutrición y amenorrea hipotalámica funcional: Neuropéptidos periféricos (Leptina, Adiponectina, Ghrelina y su relación con la homeostasis metabólica

    Directory of Open Access Journals (Sweden)

    León Fiszlejder

    2009-09-01

    AHF, promueve la oxidación de los ácidos grasos libres en el músculo esquelético, produce una reducción de triglicéridos en esos tejidos, inhibe directamente la captación y oxidación de los ácidos grasos libres en el hígado, disminuyendo también los triglicéridos en esta víscera. Estas acciones inducen el aumento de la sensibilidad a la insulina, una de las características en la patología de estas pacientes. Además, esta citokina disminuye la liberación de glucosa desde el hígado y músculo esquelético y estimula directamente la captación de glucosa en estos tejidos, mediante la activación de la AMP proteinkinasa. En consecuencia, la elevación de la adiponectina jugaría un rol de colaboración en el mantenimiento de la homeostasis metabólica-energética en condiciones de mal nutrición, como la que impera en la anorexia nerviosa y en otras causas de AHF. La osteosporosis, la inmunodepresión, el aumento del riesgo cardiovascular y la AHF pueden ser interpretados como efectos que derivan de procesos de adaptación que llevan a cabo hormonas hipotalámicas y neuropétidos periféricos. La amenorrea podría ser considerada un efecto protector.Functional hypothalamic amenorrhea (FHA is usually associated with an inadequate qualitative and quantitative diet which influences the energetic balance, modifies the body composition and produces hormonal reactions in order to keep metabolic homeostasis. This adaptive process is regulated by a "central circuit" (hypothalamic hormones, a "peripheral circuit" originated by adipocyte tissue (leptin, adiponectin, among other cytokines and the superior gastrointestinal tract through a neuropetide: ghrelin. Leptin acts in the hypothalamus stimulating the synthesis of MSH and inhibits the NPY and the AgRP (Agouti-related-peptide both with orexigen action. NPY stimulates CRH and both inhibit GnRH in the hypothalamus. Low levels of leptin in FHA increases NPY-CRH system blocking Gn-RH pulsatility, a key process in