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Sample records for rat ventromedial hypothalamic

  1. Resistance to adenovirally induced hyperleptinemia in rats. Comparison of ventromedial hypothalamic lesions and mutated leptin receptors.

    Science.gov (United States)

    Koyama, K; Shimabukuro, M; Chen, G; Wang, M Y; Lee, Y; Kalra, P S; Dube, M G; Kalra, S P; Newgard, C B; Unger, R H

    1998-01-01

    Leptin regulates appetite and body weight via hypothalamic targets, but it can act directly on cultured pancreatic islets to regulate their fat metabolism. To obtain in vivo evidence that leptin may act peripherally as well as centrally, we compared the effect of adenovirally induced hyperleptinemia on food intake, body weight, and islet fat content in ventromedial hypothalamic-lesioned (VMHL) rats, sham-lesioned (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated. Infusion with recombinant adenovirus containing the rat leptin cDNA increased plasma leptin by approximately 20 ng/ml in VMHL and ZDF rats but had no effect on their food intake, body weight, or fat tissue weight. Caloric matching of hyperphagic VMHL rats to SL controls did not reduce their resistance to hyperleptinemia. Whereas prediabetic ZDF rats had a fourfold elevation in islet fat, in VMHL rats islet fat was normal and none of them became diabetic. Isolated islets from ZDF rats were completely resistant to the lipopenic action of leptin, while VMHL islets exhibited 50% of the normal response; caloric matching of VMHL rats to SL controls increased leptin responsiveness of their islets to 92% of controls. We conclude that leptin regulation of adipocyte fat requires an intact VMH but that islet fat content is regulated independently of the VMH. PMID:9710441

  2. Ventromedial hypothalamic knife-cut lesions in rats resistant to dietary obesity.

    Science.gov (United States)

    Oku, J; Bray, G A; Fisler, J S; Schemmel, R

    1984-06-01

    The effects of ventromedial hypothalamic (VMH) knife-cut lesions on food intake and body weight of S 5B/Pl rats, which are normally resistant to obesity when eating a high-fat diet, were examined in two experiments. In the first experiment body weight increased only slightly after VMH knife-cut lesions when animals were fed pelleted laboratory chow or a 10% corn oil diet. When eating the 30% corn oil diet, however, body weight increased in the VMH knife-cut rats. In the second experiment VMH knife-cut lesions produced a small weight gain in rats fed the 10% fat diet; this manipulation also increased food intake and disrupted the normal diurnal feeding pattern. Changes in the weight of the liver, interscapular brown adipose tissue, and white adipose tissue paralleled the changes in body weight. Plasma insulin increased in the rats eating the 30% corn oil diet ad libitum but not in the VMH-lesioned animals pair fed to the sham-operated rats. Incorporation of 3H from 3H2O into lipid was significantly increased in white fat of animals with VMH knife cuts. Similar results were obtained from incubation of adipose tissue in vitro with insulin and radioactively labeled glucose. These studies show that hypothalamic knife-cut lesions can remove the resistance of the S 5B/Pl rats to obesity when they are fed a high-fat diet.

  3. Effects of oral and parenteral quinine on rats with ventromedial hypothalamic knife-cut obesity.

    Science.gov (United States)

    Oku, J; Bray, G A; Fisler, J S

    1984-06-01

    The addition of quinine to the food reversed the obesity in rats with hypothalamic hyperphagia induced by knife cuts. Similarly, the injection of quinine into rats with hypothalamic knife cuts reduced food intake and body weight but the effects were smaller than those observed when quinine was added to the diet. Urinary quinine excretion was similar by the oral and parenteral routes. The food intake of the knife-cut animals receiving quinine gradually fell to the same level as in the sham-operated animals receiving quinine by either route. The weights of retroperitoneal fat pads were related to the weights of the animals and were reduced in the quinine-treated groups. Plasma insulin concentrations were significantly higher in the knife-cut animals and were reduced toward control levels by quinine treatment. Gluconeogenesis, measured by incorporation of radioactivity from labeled bicarbonate into glucose, was unaffected by treatment with quinine or by knife cuts. Lipogenesis from tritiated water in vivo was not different between treatment groups in the liver or retroperitoneal fat pads. However, in vivo lipogenesis was reduced in knife-cut rats fed ad libitum compared with quinine-treated rats. The response of lipogenesis to insulin in vitro was also not different between treatment groups. These data suggest that a major part of the reduction in food intake in hyperphagic rats eating a quinine-adulterated diet is due to postingestional events.

  4. Time course of the estradiol-dependent induction of oxytocin receptor binding in the ventromedial hypothalamic nucleus of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, A.E.; Ball, G.F.; Coirini, H.; Harbaugh, C.R.; McEwen, B.S.; Insel, T.R. (National Institute of Mental Health, Poolesville, MD (USA))

    1989-09-01

    Oxytocin (OT) transmission is involved in the steroid-dependent display of sexual receptivity in rats. One of the biochemical processes stimulated by the ovarian steroid 17 beta-estradiol (E2) that is relevant to reproduction is the induction of OT receptor binding in the ventromedial hypothalamic nucleus (VMN). The purpose of these experiments was to determine if E2-induced changes in OT receptor binding in the VMN occur within a time frame relevant to cyclic changes in ovarian steroid secretion. OT receptor binding was measured in the VMN of ovariectomized rats implanted for 0-96 h with E2-containing Silastic capsules. The rate of decay of OT receptor binding was measured in another group of animals 6-48 h after capsule removal. Receptors were labeled with the specific OT receptor antagonist ({sup 125}I)d(CH2)5(Tyr(Me)2,Thr4,Tyr-NH2(9))OVT, and binding was measured with quantitative autoradiographic methods. In addition, plasma E2 levels and uterine weights were assessed in animals from each treatment condition. Significant increases in E2-dependent OT receptor binding and uterine weight occurred within 24 h of steroid treatment. After E2 withdrawal, OT receptor binding and uterine weight decreased significantly within 24 h. These results are consistent with the hypothesis that steroid modulation of OT receptor binding is necessary for the induction of sexual receptivity.

  5. Ventromedial and medial preoptic hypothalamic ibotenic acid lesions potentiate systemic morphine analgesia in female, but not male rats.

    Science.gov (United States)

    Cataldo, Giuseppe; Lovric, Jelena; Chen, Chia-Chien; Pytte, Carolyn L; Bodnar, Richard J

    2010-12-25

    Sex differences in systemic morphine analgesia occur with male rodents displaying significantly greater analgesic magnitudes and potencies than females. Neonatal androgenization, and to a lesser degree, adult ovariectomy enhance systemic morphine analgesia in female rats, implicating both organizational and activational effects of gonadal hormones. The neuroanatomical circuits sensitive to sex-related hormones by which females display a smaller opiate analgesic effect is not clear, but the ventromedial (VMH) and medial preoptic (MPOA) hypothalamic nuclei are critical in the monitoring of estradiol and other sex hormone levels. To assess the contribution of these nuclei to sex and adult gonadectomy differences in systemic morphine analgesia, intact male, intact female and adult ovariectomized (OVEX) female rats received bilateral saline (SAL) or ibotenic acid (IBO) microinjections into either the VMH or MPOA. Following surgeries, baseline tail-flick latencies over 120 minutes (min) were assessed over 4 days in all nine groups with intact females tested in the estrus phase of their cycle. All animals then received an ascending series of morphine (1.0, 2.5, 5.0, 7.5, 10.0mg/kg) injections 30min prior to the tail-flick test time course with 8-12 day inter-injection intervals between doses. Baseline latencies failed to differ between SAL-treated intact males and females, but were significantly higher in SAL-treated OVEX females. Both VMH IBO and MPOA IBO lesions increased baseline latencies in intact male and female rats, but not in OVEX females. SAL-treated intact males (ED(50)=4.0mg/kg) and SAL-treated OVEX females (ED(50)=3.5mg/kg) displayed significantly greater potencies of systemic morphine analgesia than SAL-treated intact females (ED(50)=6.3mg/kg), confirming previous gender and gonadectomy differences. Neither VMH IBO (ED(50)=3.7 mg/kg) nor MPOA IBO (ED(50)=4.1mg/kg) males differed from SAL-treated males in the potency of systemic morphine analgesia. In

  6. Metabolic effects of chronic T3 administration in the hypothalamic paraventricular and ventromedial nucleus in male rats

    NARCIS (Netherlands)

    Zhang, Z; Foppen, E; Su, Y; Bisschop, P H; Kalsbeek, A; Fliers, E; Boelen, A

    2016-01-01

    Thyroid hormone is a key regulator of energy metabolism. Apart from its direct effects on peripheral metabolism, thyroid hormone exerts acute metabolic effects via distinct nuclei within the hypothalamus. Recently, we developed a method for chronic and local intra-hypothalamic triiodothyronine (T3)

  7. VENTROMEDIAL HYPOTHALAMIC REGULATION OF HORMONAL AND METABOLIC RESPONSES TO EXERCISE

    NARCIS (Netherlands)

    Vissing, John; Wallace, Jo L.; Scheurink, Anton J.W.; Galbo, Henrik; Steffens, Anton B.

    1989-01-01

    Recent studies have indicated a neural regulation of hormonal and metabolic responses to exercise. Studies on the ventromedial hypothalamus (VMH) suggest that the VMH might be involved in neural control of exercise metabolism. We therefore studied 25 rats with or without Marcain-anesthetized VMH (Ma

  8. Guipi decoction effects on arginine vasopressin protein and gene expression in the hippocampus, ventromedial hypothalamic nucleus, and prefrontal lobe in rats with spleen deficiency

    Institute of Scientific and Technical Information of China (English)

    Huinan Qian; Xueqin Hu; Libo Shen

    2008-01-01

    BACKGROUND: Arginine vasopressin has been shown to enhance learning in experimental animal models.OBJECTIVE: To determine whether Guipi decoction enhances memory and learning by increasing arginine vasopressin levels, and to verify the influence of Guipi decoction on arginine vasopressin protein and gene expression in the hippocampal CAI region, prefrontal lobe cortex, and ventral nucleus of hypothalamus in rats with spleen deficiency.DESIGN, TIME AND SETTING: The randomized, neuropharmacological, control study was performed in the College of Basic Medical Sciences, Beijing University of Chinese Medicine between March 2002 and March 2005.MATERIALS: Sixty, healthy, male, Wistar rats were used to establish spleen deficiency models according to the traditional Chinese medicine principle of bitter drugs for purgation, improper diet, and overstrain. Arginine vasopressin-I polyclonal anti-rabbit antibody immunohistocbemistry kit and arginine vasopressin in situ hybridization kit were provided by Department of Neuroanatomy in Shanghai Second Military Medical University of Chinese PLA.METHODS: Sixty rats were divided into five groups at random: normal control (n = 11), model (n = 13), Guipi decoction (n = 12), recipe control A (n = 12), and recipe control B groups (n = 12). Rats in the latter four groups received 7.5 g/kg of the drugs by intragastric administration each morning, which comprised Dahuang, Houpu, and Zhishi, prepared at a ratio of 2:1 : 1. The rats were lasted every other day, but were allowed free access to water at all times. The rats were forced to swim in 25℃ water until fatigued. Rats in the Guipi decoction and two recipe control groups were intragastrically administered 7.5 g/kg Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellets, respectively, each afternoon. Rats in the normal group were intragastrically administered the same amount of normal saline. All rats were treated for 6 weeks.MAIN OUTCOME MEASURES: At 6 weeks after drug

  9. Ventromedial hypothalamic mediation of photoperiodic gonadal responses in male Syrian hamsters.

    Science.gov (United States)

    Bae, H H; Mangels, R A; Cho, B S; Dark, J; Yellon, S M; Zucker, I

    1999-10-01

    Short day lengths induce testicular regression in seasonally breeding Syrian hamsters. To test whether the ventromedial hypothalamus is necessary to maintain reproductive quiescence once testicular regression has been achieved, photoregressed male hamsters were subjected to lesions of the ventromedial hypothalamus (VMHx), pinealectomy (Pinx), or sham operation (Sham). VMHx hamsters underwent accelerated gonadal recrudescence compared to Pinx and Sham hamsters. Recovery of prolactin concentrations (PRL) to values characteristic of long-day hamsters was hastened in the VMHx animals compared to Sham hamsters. Concentrations of follicle stimulating hormone (FSH) increased prematurely in both the VMHx and Pinx animals, beginning a few weeks after surgery. By the time the gonads had undergone recrudescence and the hamsters were refractory to melatonin, PRL and FSH concentrations had returned to baseline long-day values in all groups; there was no evidence of hypersecretion of either hormone in any of the animals with lesions. Melatonin concentrations of VMHx hamsters did not differ from those of sham-operated animals, but because only a single determination was made, it remains possible that VMH damage altered the duration of nightly melatonin secretion. An intact VMH appears to be essential for the continued maintenance of reproductive suppression induced by exposure to short day lengths; these and earlier findings suggest that the VMH-dorsomedial hypothalamic complex mediates regression of the reproductive apparatus during decreasing day lengths of late summer and early autumn and also is necessary to sustain regression during the winter months.

  10. The nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.

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    Lina Sabra-Makke

    Full Text Available BACKGROUND: The nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hypothalamus compared to peripheral tissues. METHODOLOGY/PRINCIPAL FINDINGS: Using hyperinsulinemic-euglycemic clamps and insulinopenic mice, we show that insulin upregulates its expression in the hypothalamus. Immunofluorescence studies demonstrate that COUP-TFII gene expression is restricted to a subpopulation of ventromedial hypothalamic neurons expressing the melanocortin receptor. In GT1-7 hypothalamic cells, the MC4-R agonist MTII leads to a dose dependant increase of COUP-TFII gene expression secondarily to a local increase in cAMP concentrations. Transfection experiments, using a COUP-TFII promoter containing a functional cAMP responsive element, suggest a direct transcriptional activation by cAMP. Finally, we show that the fed state or intracerebroventricular injections of MTII in mice induce an increased hypothalamic COUP-TFII expression associated with a decreased hepatic and pancreatic COUP-TFII expression. CONCLUSIONS/SIGNIFICANCE: These observations strongly suggest that hypothalamic COUP-TFII gene expression could be a central integrator of insulin and melanocortin signaling pathway within the ventromedial hypothalamus. COUP-TFII could play a crucial role in brain integration of circulating signal of hunger and satiety involved in energy balance regulation.

  11. Hypothalamic Ventromedial Lin28a Enhances Glucose Metabolism in Diet-Induced Obesity.

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    Kim, Jung Dae; Toda, Chitoku; Ramírez, Cristina M; Fernández-Hernando, Carlos; Diano, Sabrina

    2017-08-01

    The Lin28a/Let-7 axis has been studied in peripheral tissues for its role in metabolism regulation. However, its central function remains unclear. Here we found that Lin28a is highly expressed in the hypothalamus compared with peripheral tissues. Its expression is positively correlated with positive energy balance, suggesting a potential central role for Lin28a in metabolism regulation. Thus, we targeted the hypothalamic ventromedial nucleus (VMH) to selectively overexpress (Lin28aKI(VMH) ) or downregulate (Lin28aKD(VMH) ) Lin28a expression in mice. With mice on a standard chow diet, body weight and glucose homeostasis were not affected in Lin28aKI(VMH) or Lin28aKD(VMH) mice. On a high-fat diet, although no differences in body weight and composition were observed, Lin28aKI(VMH) mice showed improved glucose tolerance and insulin sensitivity compared with controls. Conversely, Lin28aKD(VMH) mice displayed glucose intolerance and insulin resistance. Changes in VMH AKT activation of diet-induced obese Lin28aKI(VMH) or Lin28aKD(VMH) mice were not associated with alterations in Let-7 levels or insulin receptor activation. Rather, we observed altered expression of TANK-binding kinase-1 (TBK-1), which was found to be a direct Lin28a target mRNA. VMH-specific inhibition of TBK-1 in mice with diet-induced obesity impaired glucose metabolism and AKT activation. Altogether, our data show a TBK-1-dependent role for central Lin28a in glucose homeostasis. © 2017 by the American Diabetes Association.

  12. Reduction of high fat diet-induced obesity after chronic administration of brain-derived neurotrophic factor in the hypothalamic ventromedial nucleus

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    Godar, Rebecca; Dai, Yuqiao; Bainter, Heather; Billington, Charles; Kotz, Catherine M.; Wang, ChuanFeng

    2011-01-01

    An acute injection of brain-derived neurotrophic factor (BDNF) in the hypothalamic ventromedial nucleus (VMN) decreases body weight by reducing feeding and increasing energy expenditure (EE) in animals on standard laboratory chow. Animals have divergent responses to high fat diet (HFD) exposure, with some developing obesity and others remaining lean. In the current study we tested the hypothesis that BDNF in the VMN reduces HFD-induced obesity. Seventy-two 10-week old rats were allowed HFD ad libitum for 8 weeks and then prepared with bilateral VMN cannulae. Animals were then divided into tertiles based on their fat mass rank: high, intermediate and low (H, I, & L). Each group was further divided into 2 subgroups: BDNF (1 μg) or control (artificial cerebrospinal fluid, aCSF); then injected every other day for 20 days according to subgroup. Energy intake, body weight and body composition were measured. Other metabolic indices were measured before and after treatment. In parallel, another 12 rats were fed control diet (CD), VMN-cannulated and injected with aCSF. HFD exposure induced obesity in the H group, with a significant increase in energy intake, body weight, fat mass, liver size and serum glucose, insulin and leptin. BDNF significantly reduced body weight and fat mass in all phenotypes; while it reduced energy intake only in the I group. However, BDNF increased EE, spontaneous physical activity and fat oxidation in the H group, suggesting that BDNF-induced EE elevation contributed to reduction of body weight and fat mass. Chronic VMN BDNF reduced insulin elevation and/or reversed hyperleptinemia. These data suggest that the VMN is an important site of action for BDNF reduction of HFD-induced obesity. PMID:21856381

  13. Physical exercise-induced cardiovascular adjustments are modulated by muscarinic cholinoceptors within the ventromedial hypothalamic nucleus

    National Research Council Canada - National Science Library

    Wanner, S P; Guimarães, J B; Pires, W; La Guardia, R B; Haibara, A S; Marubayashi, U; Coimbra, C C; Lima, N R V

    2010-01-01

    .... After recovering from surgery, the rats were familiarized to running on a treadmill. The animals then had a polyethylene catheter implanted into the left carotid artery to measure blood pressure...

  14. Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.

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    Paula Mera

    Full Text Available Lipid metabolism in the ventromedial hypothalamus (VMH has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH, long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT and reduced vesicular glutamate transporter 2 (VGLUT2 expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH.

  15. The ventromedial hypothalamic nucleus in the zebra finch (Taeniopygia guttata): Afferent and efferent projections in relation to the control of reproductive behavior.

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    Wild, J Martin

    2017-08-15

    Sex-specific mating behaviors occur in a variety of mammals, with the medial preoptic nucleus (POM) and the ventromedial hypothalamic nucleus (VMH) mediating control of male and female sexual behavior, respectively. In birds, likewise, POM is predominantly involved in the control of male reproductive behavior, but the degree to which VMH is involved in female reproductive behavior is unclear. Here, in male and female zebra finches, a combination of aromatase immunohistochemistry and conventional tract tracing facilitated the definition of two separate but adjacent nuclei in the basal hypothalamus: an oblique band of aromatase-positive (AR+) neurons, and ventromedial to this, an ovoid, aromatase-negative (AR-) nucleus. The AR- nucleus, but not the AR+ nucleus, was here shown to receive a projection from rostral parts of the thalamic auditory nucleus ovoidalis and from the nucleus of the tractus ovoidalis. The AR- nucleus also receives an overlapping, major projection from previously uncharted regions of the medial arcopallium and a minor projection from the caudomedial nidopallium. Both the AR- and the AR+ nuclei project to the intercollicular nucleus of the midbrain. No obvious sex differences in either the pattern of AR immunoreactivity or of the afferent projections to the AR- nucleus were observed. The significance of these results in terms of the acoustic control of avian reproductive behavior is discussed, and a comparison with the organization of VMH afferents in lizards suggests a homologous similarity of the caudal telencephalon in sauropsids. © 2017 Wiley Periodicals, Inc.

  16. Topographic Organization of Projections from the Amygdala to the Hypothalamus of the Rat

    NARCIS (Netherlands)

    Ono, Taketoshi; Luiten, Paul G.M.; Nishijo, Hisao; Fukuda, Masaji; Nishino, Hitoo

    1985-01-01

    Afferent fibers from the amygdala to subdivisions of lateral, ventromedial and dorsomedial hypothalamic nuclei were investigated in rat by retrograde transport of horseradish peroxidase. Small (intranuclear size) peroxidase deposits were placed in hypothalamic nuclei by iontophoresis of a tracer sol

  17. EFFECT OF ANESTHETIZING THE REGION OF THE PARAVENTRICULAR HYPOTHALAMIC NUCLEI ON ENERGY-METABOLISM DURING EXERCISE IN THE RAT

    NARCIS (Netherlands)

    VANDIJK, G; VISSING, J; STEFFENS, AB; GALBO, H

    1994-01-01

    The ventromedial and posterior hypothalamic nuclei are known to influence glucoregulation during exercise. The extensive projections of the paraventricular hypothalamic nucleus (PVN) to the sympathetic nervous system suggest that the PVN also may be involved in glucoregulation during exercise. The r

  18. Nutritional Recovery Promotes Hypothalamic Inflammation in Rats during Adulthood

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    Hellen Barbosa Farias Silva

    2014-01-01

    Full Text Available We evaluated whether protein restriction in fetal life alters food intake and glucose homeostasis in adulthood by interfering with insulin signal transduction through proinflammatory mechanisms in the hypothalamus and peripheral tissues. Rats were divided into the following: a control group (C; a recovered group (R; and a low protein (LP group. Relative food intake was greater and serum leptin was diminished in LP and R compared to C rats. Proinflammatory genes and POMC mRNA were upregulated in the hypothalamus of R group. Hypothalamic NPY mRNA expression was greater but AKT phosphorylation was diminished in the LP than in the C rats. In muscle, AKT phosphorylation was higher in restricted than in control animals. The HOMA-IR was decreased in R and C compared to the LP group. In contrast, the Kitt in R was similar to that in C and both were lower than LP rats. Thus, nutritional recovery did not alter glucose homeostasis but produced middle hyperphagia, possibly due to increased anorexigenic neuropeptide expression that counteracted the hypothalamic inflammatory process. In long term protein deprived rats, hyperphagia most likely resulted from increased orexigenic neuropeptide expression, and glucose homeostasis was maintained, at least in part, at the expense of increased muscle insulin sensitivity.

  19. Effects of black cohosh and estrogen on the hypothalamic nuclei of ovariectomized rats at different temperatures.

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    Hui, Zhang; Xiaoyan, Ma; Mukun, Yang; Ke, Wang; Liyuan, Yang; Sainan, Zhu; Jing, Jia; Lihua, Qin; Wenpei, Bai

    2012-08-01

    Cimicifuga racemosa (L.) Nutt. (CR), known as black cohosh, has been used in Europe as a medicinal plant for more than a century and its roots have been widely used for the treatment of menopausal symptoms. Remifemin, the main ingredient in liquid or tablet medications prepared from isopropyl alcohol extracts of black cohosh rhizome, has also been evaluated in clinical studies. To observe changes in the expression of the c-Fos protein in the hypothalamic nuclei of four groups of rats-sham-operated group (SHAM), ovariectomized (OVX) group, ovariectomized group treated with estrogen(OVX+E), and ovariectomized group treated with the isopropanol extract of Cimicifuga racemosa (OVX+ICR)-and to investigate the mechanisms of black cohosh and estrogen that take place in the hypothalamic nuclei of ovariectomized rats. Fifty rats were assigned to each of the four groups and placed in incubators at 4 °C, 10 °C, 25 °C, 33 °C, or 38 °C for 2 h. They were then anesthetized, and their brains were removed after heart perfusion. c-Fos expression in the hypothalamic nuclei was evaluated using immunohistochemical methods. In the median preoptic nucleus (MnPO), ventromedial preoptic nucleus (VMPO), and suprachiasmatic nucleus (SCh) of the SHAM group, in the anterior hypothalamic area (AH) and supraoptic nucleus (SO) of all four groups, and in the paraventricular nucleus (PVN) of the SHAM, OVX and OVX+E groups, the c-Fos-positive cell densities all changed in a similar manner: the cell density decreased when the temperature was less than 25 °C and the density increased when the temperature was greater than 25 °C, demonstrating a V-type curve. The c-Fos density was lowest at 25°C. The other nuclei demonstrated irregular changes. The positive cell densities in the MnPO, AH, and PVN of the SHAM, OVX+E, and OVX+ICR groups were greater than the densities measured in the OVX group at all temperatures, except 25 °C. Positive cell densities in the SHAM, OVX+E, and OVX+ICR groups were

  20. [Bioelectric and vegetative reactions of the rat to stimulation of the ventromedial hypothalamus].

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    Vorob'eva, T M; Katalevskaia, L G; Kirzhner, V M

    1984-01-01

    Neurophysiological and correlational analysis was carried out to investigate the influence of stimulation of negative zones in the ventromedial hypothalamus on dynamics of electroencephalographic and vegetative parameters. The stimulation used led to an appearance of theta-rhythm initially in the stimulated structure, followed by an increase of plasticity of the system of bioelectrogenesis and regulation of vegetative functions. Stimulation of the negative zones of the ventromedial hypothalamus led to a formation of pathological excitation focus mainly at the limbic level with special cyclic type of cortico-subcortical relations. Increase of rigidity of the systems of electrogenesis and regulation of vegetative functions was accompanied by a formation of closed reverberatory cycle of integrations of the hypothalamus, hippocampus, and neocortex and by a change in autocorrelational functions reflecting an increase of general synchroneity .

  1. Peripheral injection of ghrelin induces Fos expression in the dorsomedial hypothalamic nucleus in rats

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    Kobelt, Peter; Wisser, Anna-Sophia; Stengel, Andreas; Goebel, Miriam; Inhoff, Tobias; Noetzel, Steffen; Veh, Rüdiger W.; Bannert, Norbert; van der Voort, Ivo; Wiedenmann, Bertram; Klapp, Burghard F.; Taché, Yvette; Mönnikes, Hubert

    2009-01-01

    Peripheral ghrelin has been shown to act as a gut–brain peptide exerting a potent orexigenic effect on food intake. The dorsomedial nucleus of the hypothalamus (DMH) is innervated by projections from other brain areas being part of the network of nuclei controlling energy homeostasis, among others NPY/AgRP-positive fibers arising from the arcuate nucleus (ARC). The aim of the study was to determine if peripherally administered ghrelin affects neuronal activity in the DMH, as assessed by Fos expression. The number of Fos positive neurons was determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), ARC, ventromedial hypothalamic nucleus (VMH), nucleus of the solitary tract (NTS) and in the area postrema(AP) in non-fasted Sprague–Dawley rats in response to intraperitoneally (ip) injected ghrelin (3 nmol/rat) or vehicle (0.15 M NaCl). Peripheral ghrelin induced a significant increase in the number of Fos-ir positive neurons/section compared with vehicle in the ARC (mean±SEM: 49±2 vs. 23±2 neurons/section, p=0.001), PVN (69±5 vs. 34±3, p=0.001), and DMH (142±5 vs. 83±5, p<0.001). Fos-ir positive neurons were mainly localized within the ventral part of the DMH. No change in Fos expression was observed in the VMH (53±8 vs. 48±6, p=0.581), NTS (42±2 vs.40±3, p=0.603), and in the AP (7±1 vs. 5±1, p=0.096). Additional double-labelling with anti-Fos and anti-AgRP revealed that Fos positive neurons in the DMH were encircled by a network of AgRP-ir positive fibers. These data indicate that peripheral ghrelin activates DMH neurons and that NPY-/AgRP-positive fibers may be involved in the response. PMID:18329635

  2. Temporal changes in the expression of brain-derived neurotrophic factor mRNA in the ventromedial nucleus of the hypothalamus of the developing rat brain.

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    Sugiyama, Nobuhiro; Kanba, Shigenobu; Arita, Jun

    2003-07-04

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which is important for the growth, differentiation, and survival of neurons during development. We have performed a detailed mapping of BDNF mRNA in the neonatal rat brain using a quantitative in situ hybridization technique. At postnatal day (PND) 4, hypothalamic structures showed only modest expression of BDNF mRNA, with the exception of the ventromedial nucleus (VMN), where expression was higher than that detected in the hippocampus. Abundant BDNF mRNA was also found in the bed nucleus of the anterior commissure, retrosplenial granular cortex, and the posteroventral part of the medial amygdaloid nucleus. Messenger RNAs encoding other neurotrophins, including nerve growth factor (NGF) and neurotrophin-3 (NT-3) and the BDNF receptor trkB, were not selectively localized in neonatal VMN. During subsequent developmental stages, BDNF mRNA expression in the VMN changed dynamically, peaking at PND 4 and falling to minimal levels in the adult brain. In contrast, the low levels of BDNF mRNA observed in the CA3 region of the hippocampus increased to adult levels following PND 10. As the VMN undergoes sexual differentiation, we compared BDNF, NGF, NT-3, and trkB mRNA expression in the VMN in males and females at embryonic day 20 and PND 4, but found no differences between them. These results suggest that localized and high level expression of BDNF mRNA in the neonatal VMN plays an important role in its neural organization and functional development.

  3. Electrical stimulation of the substantia nigra reticulata : Detection of neuronal extracellular GABA in the ventromedial thalamus and its regulatory mechanism using microdialysis in awake rats

    NARCIS (Netherlands)

    Timmerman, W; Westerink, BHC

    1997-01-01

    A combination of electrical stimulation and microdialysis was used to study the nigrothalamic gamma aminobutyric acid (GABA)ergic system and its regulatory mechanisms in awake rats. Extracellular GABA levels in the ventromedial nucleus of the thalamus were detected in S-min fractions collected befor

  4. HYPOTHALAMIC BLOOD-FLOW REMAINS UNALTERED FOLLOWING CHRONIC NITRIC-OXIDE SYNTHASE BLOCKADE IN RATS

    NARCIS (Netherlands)

    BENYO, Z; SZABO, C; STUIVER, BT; BOHUS, B; SANDOR, P

    1995-01-01

    The effect of the chronic oral application of N-G-nitro-L-arginine methyl eater (L-NAME), a potent inhibitor of nitric oxide (NO) production, was studied on hypothalamic blood flow (HBF) and hypothalamic nitric oxide synthase (NOS) activity in rats. L-NAME was dissolved in the drinking water, in a c

  5. Neuronal glucoprivation enhances hypothalamic histamine turnover in rats.

    Science.gov (United States)

    Oohara, A; Yoshimatsu, H; Kurokawa, M; Oishi, R; Saeki, K; Sakata, T

    1994-08-01

    Histamine (HA) turnover in the rat hypothalamus following insufficient energy supply due to glucoprivation was examined after administration of insulin or 2-deoxy-D-glucose (2-DG). HA turnover was assessed by accumulation of tele-methylhistamine (t-MH), a major metabolite of brain HA, following administration of pargyline. Intraperitoneal injection of 1, 2, and 4 U/kg of insulin, which had no influence on steady-state levels of HA and t-MH, increased pargyline-induced accumulation of t-MH. Accumulation of t-MH due to pargyline was inversely related to the concomitant plasma glucose concentration after different doses of insulin. The level of t-MH accumulated by pargyline did not change compared with that of controls, when a euglycemic condition was maintained or insulin at a dose of 6 mU per rat was infused into the third cerebroventricle. Intracerebroventricular infusion of 24 mumol per rat of 2-DG, which had no influence on steady-state levels of HA and t-MH, increased the level of t-MH enhanced by pargyline. The results indicate that an increase in hypothalamic HA turnover in response to glucoprivation may be involved in homeostatic regulation of energy metabolism in the brain.

  6. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats

    National Research Council Canada - National Science Library

    Eduardo R. Ropelle; José R. Pauli; Patrícia Prada; Dennys E. Cintra; Guilherme Z. Rocha; Juliana C. Moraes; Marisa J. S. Frederico; Gabrielle da Luz; Ricardo A. Pinho; José B. C. Carvalheira; Licio A. Velloso; Mario A. Saad; Cláudio T. De Souza

    2009-01-01

    ... in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats...

  7. Alteration of GABAergic and glycinergic mechanisms by lidocaine injection in the rostral ventromedial medulla of neuropathic rats.

    Science.gov (United States)

    Saadé, Nayef E; Al Amin, Hassen; Tchachaghian, Sima; Jabbur, Suhayl J; Atweh, Samir F

    2010-04-01

    Attenuation of neuropathic manifestations in experimental animals, by lidocaine injection in the rostral ventro-medial medulla (RVM), has been traditionally attributed to selective block of a descending pain facilitatory system. However, the presence of descending fibers carrying this effect and the selective action of lidocaine on the facilitatory neurons, have not been supported by convincing experimental evidence. The present study aimed to investigate the mechanisms underlying the hypoalgesic action of lidocaine injection in the brainstem. Several groups of rats were subjected to mononeuropathy on their left hind paws, according to the model of spared nerve injury, and were subsequently implanted with guide cannulae in the RVM. After recovery, rats received injections of lidocaine, GABA and glycine agonists or antagonists and their effects were assessed on behavioral tests of allodynia and hyperalgesia. Injections of lidocaine at doses ranging between 0.05% and 2% produced attenuation at high doses and no effects or increasing hyperalgesia at low doses. GABA and glycine agonists increased neuropathic manifestations while their antagonists elicited the opposite effects. A combined injection of GABA agonist or glycine with lidocaine (0.5%) prevented the inhibitory effects of lidocaine injection alone. Our results are in line with the abundant documentation on the alteration of the function of inhibitory neurons by lidocaine and reveal a possible action of the injected high doses on the GABAergic and glycinergic neurons in the RVM. The resulting block of the inhibitory tone exerted by these neurons can lead to a release of the descending pain inhibitory systems.

  8. Behavioral and endocrine responses of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain)

    NARCIS (Netherlands)

    Bohus, B.; Wimersma Greidanus, T.B. van; Wied, D. de

    1975-01-01

    Behavioral and endocrine profiles were established of homozygous (HO-DI) and heterozygous (HE-DI) rats with hereditary hypothalamic diabetes insipidus in comparison to Wistar strain rats. HO-DI rats were inferior in acquiring and maintaining active and passive avoidance behavior. Behavioral deficits

  9. Unilateral neuromodulation of the ventromedial hypothalamus of the rat through deep brain stimulation

    Science.gov (United States)

    Lehmkuhle, M. J.; Mayes, S. M.; Kipke, D. R.

    2010-06-01

    This study offers evidence that long-term deep brain stimulation of the ventromedial hypothalamus (VMH) can alter weight gain in mammals without affecting feeding behavior. Animals stimulated unilaterally at high frequencies of 150 or 500 Hz demonstrated increased CO2 production that decreased from prestimulation levels after the stimulation was removed. Animals stimulated for up to 6 weeks gained weight at a lower rate than normal animals or animals implanted with an electrode but not stimulated. Stimulated animals exhibited normal food and water consumption. A significant decrease in efficiency was observed during stimulation that coincided with an increase in the amount of feces produced. Whereas the weight of control animals was significantly different from week to week, the weight of stimulated animals did not change accordingly. These data suggest that the VMH may be a viable target for long-term deep brain stimulation for modulation of the neural mechanisms of metabolism. The potential therapeutic effects of deep brain stimulation of the hypothalamus are discussed.

  10. Histaminergic H1 and H2 receptors located within the ventromedial hypothalamus regulate food and water intake in rats.

    Science.gov (United States)

    Magrani, Janeide; de Castro e Silva, Emilio; Varjão, Bruno; Duarte, Gleison; Ramos, Ana Claudia; Athanazio, Rodrigo; Barbetta, Marcelo; Luz, Patricia; Fregoneze, Josmara B

    2004-09-01

    The aim of the present study was to investigate the effect of the pharmacological blockade of histamine H1 and H2 receptors located within the ventromedial hypothalamus (VMH) on overnight food and water intake and on water intake elicited by two physiological stimuli: hyperosmolarity induced by an acute intragastric salt load and water deprivation. During the overnight period, the pharmacological blockade of both H1 and H2 VMH receptors significantly increased food intake and decreased water intake. In hyperosmotic rats, the blockade of H1 VMH receptors reduced water intake, while the blockade of H2 receptors in this same region yielded no significant effect. Additionally, in water-deprived rats, the blockade of both H1 and H2 receptors located within the VMH induced a significant decrease in water intake. The inhibitory effects on drinking behavior observed in this study do not seem to be a consequence of any "illness-inducing" effect provoked by the central administration of the antihistaminergic agents employed here, because an aversion test indicated that the injection of those compounds into the VMH does not induce any "illness-like" effect. In addition, the central administration of either mepyramine or cimetidine to dehydrated and hyperosmotic rats did not produce any reduction in locomotor activity measured in an open-field arena. Injections of the antihistaminergic agents used here into the regions that circumscribe the VMH produced no significant effects on water or food intake, indicating that the actions observed here may be specifically attributed to the set of histaminergic receptors situated within the VMH.

  11. Estrogenic regulation of histamine receptor subtype H1 expression in the ventromedial nucleus of the hypothalamus in female rats.

    Directory of Open Access Journals (Sweden)

    Hiroko Mori

    Full Text Available Female sexual behavior is controlled by central estrogenic action in the ventromedial nucleus of the hypothalamus (VMN. This region plays a pivotal role in facilitating sex-related behavior in response to estrogen stimulation via neural activation by several neurotransmitters, including histamine, which participates in this mechanism through its strong neural potentiating action. However, the mechanism through which estrogen signaling is linked to the histamine system in the VMN is unclear. This study was undertaken to investigate the relationship between estrogen and histamine receptor subtype H1 (H1R, which is a potent subtype among histamine receptors in the brain. We show localization of H1R exclusively in the ventrolateral subregion of the female VMN (vl VMN, and not in the dorsomedial subregion. In the vl VMN, abundantly expressed H1R were mostly colocalized with estrogen receptor α. Intriguingly, H1R mRNA levels in the vl VMN were significantly elevated in ovariectomized female rats treated with estrogen benzoate. These data suggest that estrogen can amplify histamine signaling by enhancing H1R expression in the vl VMN. This enhancement of histamine signaling might be functionally important for allowing neural excitation in response to estrogen stimulation of the neural circuit and may serve as an accelerator of female sexual arousal.

  12. Defense of Elevated Body Weight Setpoint in Diet-Induced Obese Rats on Low Energy Diet Is Mediated by Loss of Melanocortin Sensitivity in the Paraventricular Hypothalamic Nucleus.

    Science.gov (United States)

    Luchtman, Dirk W; Chee, Melissa J S; Doslikova, Barbora; Marks, Daniel L; Baracos, Vickie E; Colmers, William F

    2015-01-01

    Some animals and humans fed a high-energy diet (HED) are diet-resistant (DR), remaining as lean as individuals who were naïve to HED. Other individuals become obese during HED exposure and subsequently defend the obese weight (Diet-Induced Obesity- Defenders, DIO-D) even when subsequently maintained on a low-energy diet. We hypothesized that the body weight setpoint of the DIO-D phenotype resides in the hypothalamic paraventricular nucleus (PVN), where anorexigenic melanocortins, including melanotan II (MTII), increase presynaptic GABA release, and the orexigenic neuropeptide Y (NPY) inhibits it. After prolonged return to low-energy diet, GABA inputs to PVN neurons from DIO-D rats exhibited highly attenuated responses to MTII compared with those from DR and HED-naïve rats. In DIO-D rats, melanocortin-4 receptor expression was significantly reduced in dorsomedial hypothalamus, a major source of GABA input to PVN. Unlike melanocortin responses, NPY actions in PVN of DIO-D rats were unchanged, but were reduced in neurons of the ventromedial hypothalamic nucleus; in PVN of DR rats, NPY responses were paradoxically increased. MTII-sensitivity was restored in DIO-D rats by several weeks' refeeding with HED. The loss of melanocortin sensitivity restricted to PVN of DIO-D animals, and its restoration upon prolonged refeeding with HED suggest that their melanocortin systems retain the ability to up- and downregulate around their elevated body weight setpoint in response to longer-term changes in dietary energy density. These properties are consistent with a mechanism of body weight setpoint.

  13. Desipramine inhibits histamine H1 receptor-induced Ca2+ signaling in rat hypothalamic cells.

    Directory of Open Access Journals (Sweden)

    Ji-Ah Kang

    Full Text Available The hypothalamus in the brain is the main center for appetite control and integrates signals from adipose tissue and the gastrointestinal tract. Antidepressants are known to modulate the activities of hypothalamic neurons and affect food intake, but the cellular and molecular mechanisms by which antidepressants modulate hypothalamic function remain unclear. Here we have investigated how hypothalamic neurons respond to treatment with antidepressants, including desipramine and sibutramine. In primary cultured rat hypothalamic cells, desipramine markedly suppressed the elevation of intracellular Ca(2+ evoked by histamine H1 receptor activation. Desipramine also inhibited the histamine-induced Ca(2+ increase and the expression of corticotrophin-releasing hormone in hypothalamic GT1-1 cells. The effect of desipramine was not affected by pretreatment with prazosin or propranolol, excluding catecholamine reuptake activity of desipramine as an underlying mechanism. Sibutramine which is also an antidepressant but decreases food intake, had little effect on the histamine-induced Ca(2+ increase or AMP-activated protein kinase activity. Our results reveal that desipramine and sibutramine have different effects on histamine H1 receptor signaling in hypothalamic cells and suggest that distinct regulation of hypothalamic histamine signaling might underlie the differential regulation of food intake between antidepressants.

  14. "On-" and "off-" cells in the rostral ventromedial medulla of rats held in thermoneutral conditions: are they involved in thermoregulation?

    Science.gov (United States)

    El Bitar, Nabil; Pollin, Bernard; Le Bars, Daniel

    2014-11-01

    In thermal neutral condition, rats display cyclic variations of the vasomotion of the tail and paws, synchronized with fluctuations of blood pressure, heart rate, and core body temperature. "On-" and "off-" cells located in the rostral ventromedial medulla, a cerebral structure implicated in somatic sympathetic drive, 1) exhibit similar spontaneous cyclic activities in antiphase and 2) are activated and inhibited by thermal nociceptive stimuli, respectively. We aimed at evaluating the implication of such neurons in autonomic regulation by establishing correlations between their firing and blood pressure, heart rate, and skin and core body temperature variations. When, during a cycle, a relative high core body temperature was reached, the on-cells were activated and within half a minute, the off-cells and blood pressure were depressed, followed by heart rate depression within a further minute; vasodilatation of the tail followed invariably within ∼3 min, often completed with vasodilatation of hind paws. The outcome was an increased heat loss that lessened the core body temperature. When the decrease of core body temperature achieved a few tenths of degrees, sympathetic activation switches off and converse variations occurred, providing cycles of three to seven periods/h. On- and off-cell activities were correlated with inhibition and activation of the sympathetic system, respectively. The temporal sequence of events was as follows: core body temperature → on-cell → off-cell ∼ blood pressure → heart rate → skin temperature → core body temperature. The function of on- and off-cells in nociception should be reexamined, taking into account their correlation with autonomic regulations. Copyright © 2014 the American Physiological Society.

  15. Connections of the juxtaventromedial region of the lateral hypothalamic area in the male rat.

    Directory of Open Access Journals (Sweden)

    Joel D Hahn

    2015-05-01

    Full Text Available Evolutionary conservation of the hypothalamus attests to its critical role in the control of fundamental behaviors. However, our knowledge of hypothalamic connections is incomplete, particularly for the lateral hypothalamic area (LHA. Here we present the results of neuronal pathway-tracing experiments to investigate connections of the LHA juxtaventromedial region, which is parceled into dorsal (LHAjvd and ventral (LHAjvv zones. Phaseolus vulgaris leucoagglutinin (PHAL, for outputs and cholera toxin B subunit (CTB, for inputs coinjections were targeted stereotaxically to the LHAjvd/v. RESULTS: LHAjvd/v connections overlapped highly but not uniformly. Major joint outputs included: Bed nuc. stria terminalis (BST, interfascicular nuc. (BSTif and BST anteromedial area, rostral lateral septal (LSr- and ventromedial hypothalamic (VMH nuc., and periaqueductal gray. Prominent joint LHAjvd/v input sources included: BSTif, BST principal nuc., LSr, VMH, anterior hypothalamic-, ventral premammillary-, and medial amygdalar nuc., and hippocampal formation (HPF field CA1. However, LHAjvd HPF retrograde labeling was markedly more abundant than from the LHAjvv; in the LSr this was reversed. Furthermore, robust LHAjvv (but not LHAjvd targets included posterior- and basomedial amygdalar nuc., whereas the midbrain reticular nuc. received a dense input from the LHAjvd alone. Our analyses indicate the existence of about 500 LHAjvd and LHAjvv connections with about 200 distinct regions of the cerebral cortex, cerebral nuclei, and cerebrospinal trunk. Several highly LHAjvd/v-connected regions have a prominent role in reproductive behavior. These findings contrast with those from our previous pathway-tracing studies of other LHA medial and perifornical tier regions, with different connectional behavioral relations. The emerging picture is of a highly differentiated LHA with extensive and far-reaching connections that point to a role as a central coordinator of behavioral

  16. Organisation of the human dorsomedial hypothalamic nucleus.

    Science.gov (United States)

    Koutcherov, Yuri; Mai, Juergen K; Ashwell, Ken W; Paxinos, George

    2004-01-19

    This study used acetylcholinesterase (AChE) histochemistry to reveal the organization of the dorsomedial hypothalamic nucleus (DM) in the human. Topographically, the human DM is similar to DM in the monkey and rat. It is wedged between the paraventricular nucleus, dorsally, and the ventromedial nucleus, ventrally. Laterally, DM borders the lateral hypothalamic area while medially it approaches the 3rd ventricle. The AChE staining distinguished two subcompartments of the human DM: the larger diffuse and the smaller compact DM. The subcompartmental organization of the human DM appears homologous to that found in the monkey and less complex than that reported in rats. Understanding of the organization of DM creates meaningful anatomical reference for physiological and pharmacological studies in the human hypothalamus.

  17. Efferent connections from the lateral hypothalamic region and the lateral preoptic area to the hypothalamic paraventricular nucleus of the rat

    DEFF Research Database (Denmark)

    Larsen, P J; Hay-Schmidt, Anders; Mikkelsen, J D

    1994-01-01

    area within the lateral hypothalamic region that consistently innervated magnocellular perikarya of the PVN. Finally, all areas of the lateral hypothalamic region contributed substantially to fibres terminating in the perinuclear shell of the PVN. These results demonstrate that anatomically distinct...

  18. Altered hypothalamic protein expression in a rat model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

  19. Effect of hypothalamic surgery on prolactin release induced by 5-hydroxytryptophan (5-HTP) in rats.

    Science.gov (United States)

    Ohgo, S; Kato, Y; Chihara, K; Imura, H; Maeda, K

    1976-12-01

    Intravenous injections of varying doses of 5-HTP (1, 3 and 5 mg/100 g body wt), a precursor of serotonin, caused a significant and dose-related increase in plasma prolactin concentrations in urethane-anesthetized rats. Increases in plasma prolactin concentrations caused by 5-HTP (1 mg/100 g body wt iv) were abolished by the concomitant administration of L-DOPA (2 mg/100 g body wt iv). Plasma prolactin levels were also significantly elevated following the injection of 5-HTP in rats with complete hypothalamic deafferentation, whereas 5-HTP had no significant effect on plasma prolactin levels in rats with extensive hypothalamic ablation. These results suggest that 5-HTP causes prolactin secretion by stimulating the serotoninergic mechanism in the hypothalamus.

  20. Hypothalamic energy balance gene responses in the Sprague-Dawley rat to supplementation of high-energy diet with liquid ensure and subsequent transfer to chow.

    Science.gov (United States)

    Archer, Z A; Rayner, D V; Barrett, P; Balik, A; Duncan, J S; Moar, K M; Mercer, J G

    2005-11-01

    Energy dense, high fat, high sugar, foods and beverages in our diet are a major contributor to the escalating global obesity problem. Here, we examine the physiological and neuroendocrine effects of feeding rats a solid high-energy (HE) diet with or without a liquid supplement (Ensure) and the consequence of subsequently transferring animals back to chow (C). Outbred Sprague-Dawley rats were fed C until 49-56 days of age, and then transferred a HE diet for 3 weeks before allocation to one of two weight-matched groups. Over the next 10 weeks, one group remained on HE diet, whereas the other had access to the liquid diet, chocolate Ensure (EN), in addition to HE diet (HE + EN). Half the rats from each group were then killed, and the remainder were returned to C for 3 weeks. Supplementation of the HE diet with EN accelerated weight gain and increased daily energy intake, adipose tissue mass, and circulating leptin levels. Transferring animals back to C caused a decrease in bodyweight in the HE + EN group, whereas HE animals were weight stable. Both groups also exhibited voluntary hypophagia, although the magnitude and duration of this response was greater in HE + EN animals. The only effect of Ensure on the hypothalamic genes studied was on tyrosine kinase B expression in the ventromedial hypothalamic nucleus (VMH), which was increased in rats given the supplement. Withdrawal of the obesogenic diets decreased gene expression for cocaine-and-amphetamine regulated transcript (CART) and dynorphin (DYN) in the arcuate nucleus (ARC), and DYN and brain-derived neurotrophic factor (BDNF) in the VMH, whereas neuropeptide Y (NPY) gene expression in the ARC was increased. These changes were independent of previous dietary history. EN supplementation generates distinct physiological responses, yet has a minimal effect on hypothalamic neuropeptide or receptor gene expression, possibly due to the development of leptin resistance. Withdrawal of obesogenic diets induces changes in

  1. EXERCISE-INDUCED SYMPATHETIC FFA MOBILIZATION IN VMH-LESIONED RATS IS NORMALIZED BY FASTING

    NARCIS (Netherlands)

    Balkan, B.; Dijk, G. van; Strubbe, J.H.; Bruggink, J.E.; Steffens, A.B.

    This study investigates whether reduced sympathetic responses during physical exercise in ventromedial hypothalamus (VMH)-lesioned obese rats are the direct result of damage to hypothalamic circuits or a secondary effect of the altered metabolism in obesity. Obese, VMH-lesioned rats and lean

  2. EXERCISE-INDUCED SYMPATHETIC FFA MOBILIZATION IN VMH-LESIONED RATS IS NORMALIZED BY FASTING

    NARCIS (Netherlands)

    Balkan, B.; Dijk, G. van; Strubbe, J.H.; Bruggink, J.E.; Steffens, A.B.

    1992-01-01

    This study investigates whether reduced sympathetic responses during physical exercise in ventromedial hypothalamus (VMH)-lesioned obese rats are the direct result of damage to hypothalamic circuits or a secondary effect of the altered metabolism in obesity. Obese, VMH-lesioned rats and lean control

  3. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats.

    Science.gov (United States)

    Ropelle, Eduardo R; Pauli, José R; Prada, Patrícia; Cintra, Dennys E; Rocha, Guilherme Z; Moraes, Juliana C; Frederico, Marisa J S; da Luz, Gabrielle; Pinho, Ricardo A; Carvalheira, José B C; Velloso, Licio A; Saad, Mario A; De Souza, Cláudio T

    2009-05-15

    Insulin signalling in the hypothalamus plays a role in maintaining body weight. The forkhead transcription factor Foxo1 is an important mediator of insulin signalling in the hypothalamus. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1 in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats. Thus, we investigated the effects of the intracerebroventricular (i.c.v.) microinfusion of Foxo1-antisense oligonucleotide (Foxo1-ASO) and evaluated the food consumption and weight gain in normal and diet-induced obese (DIO) rats. Three days of Foxo1-ASO microinfusion reduced the hypothalamic Foxo1 expression by about 85%. i.c.v. infusion of Foxo1-ASO reduced the cumulative food intake (21%), body weight change (28%), epididymal fat pad weight (22%) and fasting serum insulin levels (19%) and increased the insulin sensitivity (34%) in DIO but not in control animals. Collectively, these data showed that the Foxo1-ASO treatment blocked the orexigenic effects of Foxo1 and prevented the hyperphagic response in obese rats. Thus, pharmacological manipulation of Foxo1 may be used to prevent or treat obesity.

  4. RhodamineB increases hypothalamic cell apoptosis and disrupts hormonal balance in rats

    Institute of Scientific and Technical Information of China (English)

    DewiRatnaSulistina; RettyRatnawati; I WayanArsanaWiyasa

    2014-01-01

    Objective:To investigate whether orally exposure to rhodamineB could be changes the expression ofBax,Bcl-2 of the hypothalamic, and also levels ofFollicleStimulatingHormone (FSH) andLuteinizingHormone(LH) in female rats.Methods:Twenty eight virgin femaleWistar rats were divided into four groups, including control group, group exposed to dose of4.5,9 and18 milligram/200 gram body weight(mg/200 gBW) of rhodamineB daily for36 days.The hypothalamic expressions ofBax andBcl-2 were examined immunohistochemically.The levels of serumFSH andLH were determined by the enzyme-linked immunosorbent assay(ELISA) technique.Results:The level ofBax was significantly higher in the rhodamineB treatment group compred to control group(P<0.05).Out of the4.5,9, and18 mg/200 gBW doses of rhodamine B treatment, only the two highest doses significantly decreased theBcl-2 levels compared to the control group(P<0.05).The serumFSH andLH levels were significantly lower in all dose's rhodamineB treatment groups compared with the control(P<0.05).Conclusion:In conclusion, rhodamineB increases hypothalamic cell apoptosis and disrupts hormonal balance in rats.

  5. Effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat.

    Science.gov (United States)

    Palazzo, Enza; Marabese, Ida; Luongo, Livio; Boccella, Serena; Bellini, Giulia; Giordano, Maria Elvira; Rossi, Francesca; Scafuro, Mariantonietta; Novellis, Vito de; Maione, Sabatino

    2013-09-03

    The metabotropic glutamate receptor 7 (mGluR7) negative allosteric modulator, 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), was locally microinjected into the ventrolateral periaqueductal gray (VL PAG) and the effect on pain responses in formalin and spare nerve injury (SNI) -induced neuropathic pain models was monitored in the rat. The activity of rostral ventromedial medulla (RVM) "pronociceptive" ON and "antinociceptive" OFF cells was also evaluated. Intra-VL PAG MMPIP blocked the first and second phase of nocifensive behaviour in the formalin pain model. MMPIP increased the tail flick latency and simultaneously increased the activity of the OFF cells while inhibiting that of ON cells in rats with SNI of the sciatic nerve. MMPIP failed to modify nociceptive responses and associated RVM ON and OFF cell activity in sham rats. An increase in mGluR7 gene, protein and staining, the latter being associated with vesicular glutamate transporter-positive profiles, has been found in the VL PAG in SNI rats. Blockade of mGluR7 within the VL PAG has an antinociceptive effect in formalin and neuropathic pain models. VL PAG mGluR7 blockade offers a target for dis-inhibiting the VL PAG-RVM pathway and silencing pain in inflammatory and neuropathic pain models.

  6. [Effects of electro-acupuncture on signal transduction pathway of hypothalamic neuroendocrine system in ovariectomized rats].

    Science.gov (United States)

    Guan, Feng; Ma, Shu-Lan; Chen, Bo-Ying

    2009-06-01

    To compare the varieties and contents of the main nerval information molecules in perfusate from hypothalamic medial preoptic area (MPOA) of the rats in different sexual cycles and the ovariectomized rats treated by electro-acupuncture, so as to observe the similarities and differences of hypothalamic neuroendocrine signal transduction pathway under the physiological and pathological status, and to explore the mechanisms of neuroendocrine signal transduction of electro-acupuncture therapeutic effect in perimenopausal syndrome. The stereo localization technique and push-and-pull perfusion of the rat brain nucleus were adopted for collecting the hypothalamic MPOA perfusate of the female rats with normal sexual cycle, and also for collecting the MPOA perfusate of ovariectomized rats after electro-acupuncture treatment as acupuncture perfusate (AP). After being respectively microinjected into MPOA of the ovariectomized rats, the influence of the different perfusates on vagina cytology and serum estradiol (E2) level was observed. The contents of gonadotropin-releasing hormone (GnRH), dopamine (DA), gamma-aminobutyric acid (GABA), glutamate (Glu), aspartate (Asp) and beta-endorphin (beta-EP) in the perfusate of each group were detected by radioimmunoassay or high performance liquid chromatography, and then the varieties and contents of these substances in the perfusate of each group were compared and analyzed. The contents of neural active substances including DA, GABA, Glu, and beta-EP in the perfusate from the rats' MPOA during different stages of sexual cycle showed some regular changes. After the perfusate was microinjected respectively into the MPOA of the ovariectomized rats, the changes of animal vaginal exfoliated cells and serum E2 level showed the similar four-stage cycle characteristics as normal rats; the changes of vaginal exfoliated cells and serum E2 level of the ovariectomized rats without electro-acupuncture treatment showed the acupuncture-like effects

  7. Effects of increased hypothalamic leptin gene expression on ovariectomy-induced bone loss in rats.

    Science.gov (United States)

    Jackson, M A; Iwaniec, U T; Turner, R T; Wronski, T J; Kalra, S P

    2011-08-01

    Estrogen deficiency results in accelerated bone turnover with a net increase in bone resorption. Subcutaneous administration of leptin attenuates bone loss in ovariectomized (ovx) rats by reducing bone resorption. However, in addition to its direct beneficial effects, leptin has been reported to have indirect (central nervous system-mediated) antiosteogenic effects on bone, which may limit the efficacy of elevated serum leptin to prevent estrogen deficiency-associated bone loss. The present study evaluated the long-term effects of increased hypothalamic leptin transgene expression, using recombinant adeno-associated virus-leptin (rAAV-Lep) gene therapy, on bone mass, architecture, and cellular endpoints in sexually mature ovx Sprague-Dawley rats. Ovx rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either rAAV-Lep or rAAV-GFP (control vector encoding green fluorescent protein) and maintained for 10 weeks. Additional controls consisted of ovary-intact rats and ovx rats pair-fed to rAAV-Lep rats. Lumbar vertebrae were analyzed by micro-computed tomography and tibiae by histomorphometry. Cancellous bone volume was lower and osteoclast perimeter, osteoblast perimeter, and bone marrow adipocyte density were greater in ovx rats compared to ovary-intact controls. In contrast, differences among ovx groups were not detected for any endpoint evaluated. In conclusion, whereas estrogen deficiency resulted in marked cancellous osteopenia, increased bone turnover and marrow adiposity, increasing hypothalamic leptin transgene expression in ovx rats had neither detrimental nor beneficial effects on bone mass, architecture, or cellular endpoints. These findings demonstrate that the antiresorptive effects of subcutaneous leptin administration in ovx rats are mediated through leptin targets in the periphery. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Paraventricular hypothalamic adrenoceptors and energy metabolism in exercising rats

    NARCIS (Netherlands)

    Scheurink, Anton J.W.; Steffens, Anton B.; Gaykema, Ron P.A.

    1990-01-01

    The role of adrenoceptors in the paraventricular nucleus (PVN) in the exercise-induced changes in plasma norepinephrine (NE), epinephrine (E), corticosterone, free fatty acids (FFA), and blood glucose was investigated in rats. Exercise consisted of strenuous swimming against a countercurrent for 15

  9. Regional neurohypophysial and hypothalamic blood flow in rats during hypercapnia

    Energy Technology Data Exchange (ETDEWEB)

    Bryan, R.M. Jr.; Myers, C.L.; Page, R.B.

    1988-08-01

    Regional cerebral blood flow (rCBF) was measured in the neurohypophysis and hypothalamus in normocapnic and hypercapnic rats using (/sup 14/C)isopropyliodoamphetamine. Rats were surgically prepared using nitrous oxide and halothane and placed in plaster restraining casts. Hypercapnia was produced by increasing the fractional concentration of inspired CO/sub 2/ (FICO/sub 2/). rCBF in normocapnic rats was higher in the paraventricular nucleus, supraoptic nucleus, median eminence, and neural lobe than rates previously measured by use of diffusible tracers. During hypercapnia blood flow increased linearly with arterial PCO/sub 2/ (PACO/sub 2/) in all regions except the median eminence and neural lobe, which were not affected by hypercapnia. When rats were pretreated with phentolamine (1 mg/kg) to block the alpha-adrenergic receptors, blood flow in the median eminence and neural lobe increased significantly during hypercapnia. We conclude that blood flow in the cell bodies of the paraventricular nucleus and supraoptic nucleus is regulated differently during hypercapnia than blood flow in the nerve terminals in the median eminence and neural lobe. Furthermore, vasodilation produced by increased CO/sub 2/ is offset by alpha-receptor stimulation in the median eminence and neural lobe.

  10. Effects of Chronic Estrogen Administration in the Ventromedial Nucleus of the Hypothalamus (VMH) on Fat and Bone Metabolism in Ovariectomized Rats.

    Science.gov (United States)

    Zhang, Z; Liu, J; Veldhuis-Vlug, A G; Su, Y; Foppen, E; van der Eerden, B C J; Koedam, M; Bravenboer, N; Kalsbeek, A; Boelen, A; Fliers, E; Bisschop, P H

    2016-12-01

    Estrogen deficiency after ovariectomy (OVX) results in increased adiposity and bone loss, which can be prevented by systemic 17-β estradiol (E2) replacement. Studies in transgenic mice suggested that in addition to direct actions of estrogen in peripheral tissues, also estrogen signaling in the hypothalamus regulates fat distribution and bone metabolism. We hypothesized that the protective effect of systemic E2 on fat and bone metabolism in the OVX model is partly mediated through the ventromedial nucleus of the hypothalamus (VMH). To test this hypothesis, we determined the effect of systemic, central, and targeted VMH administration of E2 on fat and bone metabolism in OVX rats. Subcutaneous administration of E2 for 4 weeks decreased body weight, gonadal and perirenal fat, and bone formation rate in OVX rats. This effect was completely mimicked by intracerebroventricular injections of E2, once every 4 days for 4 weeks. Administration of E2 locally in the VMH by retromicrodialysis (3 h) acutely increased expression of the lipolytic gene hormone-sensitive lipase in gonadal and perirenal fat. Finally, chronic administration of E2 in the VMH for 8 weeks decreased perirenal fat but did not affect body weight, trabecular bone volume, or cortical thickness. In conclusion, we demonstrated that intracerebroventricular E2 replacement reduces body weight gain, ameliorates intraabdominal fat accumulation, and reduces bone formation in the OVX rats. E2 administration selectively in the VMH also reduced intraabdominal fat but did not affect bone metabolism.

  11. In situ hybridization of oxytocin messenger RNA: macroscopic distribution and quantitation in rat hypothalamic cell groups

    Energy Technology Data Exchange (ETDEWEB)

    Burbach, J.P.; Voorhuis, T.A.; van Tol, H.H.; Ivell, R.

    1987-05-29

    Oxytocin mRNA was detected in the rat hypothalamus by in situ hybridization to a single stranded /sup 35/S-labelled DNA probe and the distribution of oxytocin mRNA-containing cell groups was studied at the macroscopic level. Specificity of hybridization was confirmed by comparison to vasopressin mRNA hybridization in parallel tissue sections. Cell groups containing oxytocin mRNA were confined to a set of hypothalamic cell groups, i.c. the supraoptic, paraventricular, anterior commissural nuclei, nucleus circularis and scattered hypothalamic islets. These cell groups displayed similar densities of autoradiographic signals indicating that the oxytocin gene is expressed at approximately the same average level at these various sites.

  12. Effects of morphine on hypothalamic corticotropin-releasing factor (CRF, norepinephrine and dopamine in non-stressed and stressed rats.

    Directory of Open Access Journals (Sweden)

    Suemaru,Shuso

    1985-12-01

    Full Text Available The effects of morphine on the hypothalamic corticotropin-releasing factor (CRF, norepinephrine (NE and dopamine (DA concentrations were investigated in non-stressed and stressed rats. Acutely administered morphine stimulated both the synthesis and release of CRF in the hypothalamus, thereby activating the pituitary-adrenocortical system in non-stressed rats, but inhibited the stress-induced CRF synthesis and ACTH-corticosterone secretion. Either a morphine or ether-laparotomy stress reduced NE and DA concentrations in the hypothalamus. A pretreatment with morphine inhibited the stress-induced reduction in the hypothalamic NE and DA concentrations, and induced a significant increase in the DA concentration. These observations suggest that hypothalamic NE and DA are involved in morphine-induced changes in hypothalamo-pituitary-adrenocortical (HPA activity and that endogenous opiates have a role in regulating CRF secretion by interacting with hypothalamic biogenic amines.

  13. Hypothalamic inhibition of acetyl-CoA carboxylase stimulates hepatic counter-regulatory response independent of AMPK activation in rats.

    Directory of Open Access Journals (Sweden)

    Gustavo A Santos

    Full Text Available BACKGROUND: Hypothalamic AMPK acts as a cell energy sensor and can modulate food intake, glucose homeostasis, and fatty acid biosynthesis. Intrahypothalamic fatty acid injection is known to suppress liver glucose production, mainly by activation of hypothalamic ATP-sensitive potassium (K(ATP channels. Since all models employed seem to involve malonyl-CoA biosynthesis, we hypothesized that acetyl-CoA carboxylase can modulate the counter-regulatory response independent of nutrient availability. METHODOLOGY/PRINCIPAL FINDINGS: In this study employing immunoblot, real-time PCR, ELISA, and biochemical measurements, we showed that reduction of the hypothalamic expression of acetyl-CoA carboxylase by antisense oligonucleotide after intraventricular injection increased food intake and NPY mRNA, and diminished the expression of CART, CRH, and TRH mRNA. Additionally, as in fasted rats, in antisense oligonucleotide-treated rats, serum glucagon and ketone bodies increased, while the levels of serum insulin and hepatic glycogen diminished. The reduction of hypothalamic acetyl-CoA carboxylase also increased PEPCK expression, AMPK phosphorylation, and glucose production in the liver. Interestingly, these effects were observed without modification of hypothalamic AMPK phosphorylation. CONCLUSION/SIGNIFICANCE: Hypothalamic ACC inhibition can activate hepatic counter-regulatory response independent of hypothalamic AMPK activation.

  14. Perinatal undernutrition modifies cell proliferation and brain-derived neurotrophic factor levels during critical time-windows for hypothalamic and hippocampal development in the male rat.

    Science.gov (United States)

    Coupé, B; Dutriez-Casteloot, I; Breton, C; Lefèvre, F; Mairesse, J; Dickes-Coopman, A; Silhol, M; Tapia-Arancibia, L; Lesage, J; Vieau, D

    2009-01-01

    Maternal perinatal undernutrition (MPU) modifies the activity of the hypothalamic-pituitary-adrenal axis and sensitises to the development of metabolic and cognitive adult diseases. Because the hypothalamus and hippocampus are involved in the regulation of neuroendocrine activity, energy metabolism and cognition, we hypothesised that a maternal 50% food restriction (FR50) from day 14 of pregnancy (E14) until postnatal day 21 (P21) would affect the development of these structures in male rat offspring. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) and cell proliferation [analysed by 5-bromodeoxyuridine (BrdU) incorporation] were compared in both control and FR50 rats from E21 to P22. Although the pattern of the evolution of BDNF concentration and cell proliferation throughout development was not strikingly different between groups, several disturbances at specific developmental stages were observed. FR50 rats exhibited a delayed increase of hippocampal BDNF content whereas, in the hypothalamus, BDNF level was augmented from E21 to P14 and associated, at this latter stage, with an increased mRNA expression of TRkB-T2. In both groups, a correlation between BDNF content and the number of BrdU positive cells was noted in the dentate gyrus, whereas opposite variations were observed in CA1, CA2 and CA3 layers, and in the arcuate and ventromedial nuclei. In the hippocampus, P15-FR50 rats showed an increased number of BrdU positive cells in all regions, whereas, at P22, a decrease was observed in the CA2. In the hypothalamus, between E21 and P8, MPU increases the number of BrdU positive cells in all regions analysed and, until P15, marked differences were noticed in the median eminence, the paraventricular nucleus and the arcuate nucleus. Taken together, the results obtained in the present study show that MPU changes the time course of production of BDNF and cell proliferation in specific hippocampal and hypothalamic areas during sensitive

  15. 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.

  16. Centrally injected histamine increases posterior hypothalamic acetylcholine release in hemorrhage-hypotensive rats.

    Science.gov (United States)

    Altinbas, Burcin; Yilmaz, Mustafa S; Savci, Vahide; Jochem, Jerzy; Yalcin, Murat

    2015-01-01

    Histamine, acting centrally as a neurotransmitter, evokes a reversal of hemorrhagic hypotension in rats due to the activation of the sympathetic and the renin-angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. We demonstrated previously that central nicotinic cholinergic receptors are involved in the pressor effect of histamine. The aim of the present study was to examine influences of centrally administrated histamine on acetylcholine (ACh) release at the posterior hypothalamus-a region characterized by location of histaminergic and cholinergic neurons involved in the regulation of the sympathetic activity in the cardiovascular system-in hemorrhage-hypotensive anesthetized rats. Hemodynamic and microdialysis studies were carried out in Sprague-Dawley rats. Hemorrhagic hypotension was induced by withdrawal of a volume of 1.5 ml blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP), heart rate (HR), and an increase in extracellular posterior hypothalamic ACh and choline (Ch) levels by 56% and 59%, respectively. Intracerebroventricularly (i.c.v.) administered histamine (50, 100, and 200 nmol) dose- and time-dependently increased MAP and HR and caused an additional rise in extracellular posterior hypothalamic ACh and Ch levels at the most by 102%, as compared to the control saline-treated group. Histamine H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.) completely blocked histamine-evoked hemodynamic and extracellular posterior hypothalamic ACh and Ch changes, whereas H2 and H3/H4 receptor blockers ranitidine (50 nmol; i.c.v.) and thioperamide (50 nmol; i.c.v.) had no effect. In conclusion, centrally administered histamine, acting via H1 receptors, increases ACh release at the posterior hypothalamus and causes a pressor and tachycardic response in hemorrhage-hypotensive anesthetized rats.

  17. Toxic effects of methoxychlor administered subcutaneously on the hypothalamic-pituitary-testicular axis in adult rats.

    Science.gov (United States)

    Lafuente, A; Cabaleiro, T; Caride, A; Esquifino, A I

    2008-05-01

    This study was undertaken to evaluate the effects of methoxychlor MTX at the hypothalamic-pituitary-testicular axis in adult male rats. This global objective comprises three major aims: (1) to analyze the possible differential MTX effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence; (2) to evaluate effects induced by MTX exposure on gonadotropins and testosterone; 93 to elucidate whether the regulatory interactions in the hypothalamic-pituitary-testicular axis are modified by this pesticide. Animals were administered subcutaneously 25mg/kg/day of MTX for 1 month. MTX increased norepinephrine and serotonin content in anterior hypothalamus (P < or = 0.05), but decreased serotonin concentration in posterior hypothalamus (P < or = 0.05). MTX diminished serotonin turnover in anterior hypothalamus (P < or = 0.01) and decreased plasma LH (P < or = 0.001) and testosterone (P < or = 0.05) levels but those of FSH remained unmodified. We can conclude that MTX exposure: (1) could exert differential effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence, being the anterior hypothalamus the most sensitive region to the pesticide; (2) could inhibit LH and testosterone secretion without changing FSH; (3) four potential pathways might be involved in MTX effects on testosterone secretion (changing LH secretion; modifying serotonin and norepinephrine at the hypothalamic level; alterating the direct neural pathway between brain and testes; and/or by a direct effect in testes).

  18. Deafferentation of the hypothalamic paraventricular nucleus (PVN) exaggerates the sympathoadrenal system activity in stressed rats.

    Science.gov (United States)

    Ondicova, K; Kvetnansky, R; Mravec, B

    2014-07-01

    The hypothalamic paraventricular nucleus is a key structure in the regulation of the autonomic and neuroendocrine systems response to acute and chronic stress challenges. In this study, we examined the effect of a mechanical posterolateral deafferentation of the PVN on the activity of sympathoadrenal system (SAS) and hypothalamo-pituitary-adrenal (HPA) axis by measuring plasma concentrations of epinephrine (EPI), norepinephrine (NE), and corticosterone (CORT) in rats exposed to acute immobilization (IMO) stress. The surgical posterolateral deafferentation of the PVN (PVN-deaf) was performed by Halasz knife, in brain of the adult male Sprague Dawley rats, according to coordinates of a stereotaxic atlas. Sham-operated (SHAM) animals underwent a craniotomy only. The animals were allowed to recover 14 days. Thereafter, the tail artery was cannulated and the animals exposed to acute IMO for 2 h. The blood samples were collected via cannula at the time points of 0, 5, 30, 60, and 120 min of the IMO. Concentrations of plasma EPI, NE, and CORT were determined by radioimmunoassay. The IMO-induced elevation of plasma EPI concentrations in the PVN-deaf rats reached statistical significance at 60 min of the IMO, when compared to SHAM rats. Similarly, the stress-induced elevation of the NE plasma levels in the PVN-deaf rats was significantly exaggerated at all time intervals of IMO in comparison with SHAM rats, whereas plasma CORT levels were significantly reduced. In contrast to the traditional view of excitatory role of the PVN in response to stress, our data indicate that some projections from the PVN to caudally localized hypothalamic structures, the brainstem or the spinal cord, exert inhibitory effect on the SAS system activity during acute IMO stress. The data indicate that stress-induced activation of the HPA axis is partially dependent on inputs from the brainstem to the PVN.

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

    Science.gov (United States)

    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.

  20. Sleep, brain energy levels, and food intake: Relationship between hypothalamic ATP concentrations, food intake, and body weight during sleep-wake and sleep deprivation in rats.

    Science.gov (United States)

    Dworak, M; Kim, T; McCarley, R W; Basheer, R

    2011-06-01

    The feeling of hunger and feeding, a wake-state-dependent behavior, is regulated by specific centers within the hypothalamus. While paraventricular nucleus (PVN), arcuate nucleus (ARC), and dorso- and ventromedial hypothalamus (DMH/VMH) regulate feeding, the lateral hypothalamus (LH) is associated both with feeding and wake/REM sleep regulation. In order to examine the effects of sleep and wakefulness on food intake and body weight, we also measured hypothalamic ATP concentrations, which are known to be involved in feeding behavior and sleep-wake regulation. In rats, food intake and body weight was measured during a 24-h light-dark cycle and during 6 h of sleep deprivation (SD) performed by gentle handling. Tissue samples from the PVN, ARC/DMH/VMH, and LH were collected after 6 h of SD and from time-matched diurnal controls. ATP was measured by luciferin-luciferase bioluminescence assay. Across the 24-h light-dark period, rats consumed approximately 28.13±4.48 g of food and gained 5.22±1.65 g with a positive correlation between food intake and body weight. During SD, while food intake increased significantly +147.31±6.13%, they lost weight significantly (-93.29±13.64%) when compared to undisturbed controls. SD resulted in a significant decrease in ATP levels only in LH (-44.60±21.13%) with no change in PVN, ARC/DMH/VMH region when compared with undisturbed controls. The results indicate a strong overall correlation between ATP concentrations in the LH and individual food intake and suggest a sleep-wake dependent neuronal control of food intake and body weight.

  1. Differential effects of histamine on the activity of hypothalamic dopaminergic neurons in the rat.

    Science.gov (United States)

    Fleckenstein, A E; Lookingland, K J; Moore, K E

    1994-01-01

    The effect of intracerebroventricular administration of histamine on hypothalamic dopaminergic neuronal activity was estimated in male rats by measuring concentrations of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in brain regions containing terminals or perikarya of these neurons. Three distinct, regionally specific neurochemical responses were apparent. In the median eminence and intermediate lobe of the pituitary, histamine affected neither DOPAC nor dopamine concentrations, suggesting no effect on tuberoinfundibular or periventricular-hypophysial dopaminergic neuronal activity. In the medial zona incerta and in the dorsomedial, rostral periventricular and medial preoptic hypothalamic nuclei, histamine effected a dose- and time-related increase in both DOPAC and dopamine concentrations; these effects were blocked by destruction of noradrenergic neurons projecting to these regions, suggesting that these changes are attributable to noradrenergic neuronal activation, and that histamine does not affect the activity of incertohypothalamic or periventricular-preoptic dopaminergic neurons located in these brain regions. In the suprachiasmatic, caudal periventricular and paraventricular hypothalamic nuclei, histamine effected a dose- and time-related increase in DOPAC, but not dopamine, concentrations; these effects were blocked by the H1 antagonist mepyramine, but not the H2 antagonist zolantidine. Destruction of noradrenergic neurons projecting to these regions did not prevent the histamine-induced increases in DOPAC concentrations. These data indicate that histamine increases the activity of dopaminergic neurons projecting to the suprachiasmatic, caudal periventricular and paraventricular nuclei via an action at H1 receptors. Overall, these results reveal that i.c.v. administration of histamine differentially affects the activity of the various dopaminergic neuronal systems of the rat hypothalamus.

  2. Effects of fluoxetine administration on hypothalamic melanocortin system in obese Zucker rats.

    Science.gov (United States)

    Churruca, I; Portillo, M P; Casis, L; Gutiérrez, A; Macarulla, M T; Echevarría, E

    2008-06-01

    The aim of the present work was to study the potential involvement of melanocortin system in the anorectic mechanism of fluoxetine, a selective serotonin reuptake inhibitors, in obese Zucker rats. Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg; i.p.) daily for two weeks. The control group was given 0.9% NaCl solution. RT-PCR for pro-opiomelanocortin (POMC), Agouti gene related peptide (AgRP) and melanocortin receptor 4 (MC4-R) in the hypothalamus, as well as regional immunostaining for alpha-melanocyte stimulating hormone (alpha-MSH) and MC4-R were carried out. Fluoxetine administration increased POMC expression and reduced MC4-R expression in the hypothalamus, without changes in AgRP mRNA levels. Moreover, an increase in the numbers of alpha-MSH positively immunostained neural cells in the hypothalamic arcuate nucleus (ARC), as well as a significant decrease in the numbers of neural cells positively immunostained for MC4-R in the paraventricular nucleus (PVN), without changes in lateral hypothalamic area (LHA), were observed. These results suggest the involvement of alpha-MSH in central fluoxetine anorectic action.

  3. Effects of Physical Exercise on the Intestinal Mucosa of Rats Submitted to a Hypothalamic Obesity Condition.

    Science.gov (United States)

    Gomes, J R; Freitas, J R; Grassiolli, S

    2016-10-01

    The small intestine plays a role in obesity as well as in satiation. However, the effect of physical exercise on the morphology and function of the small intestine during obesity has not been reported to date. This study aimed to evaluate the effects of physical exercise on morphological aspects of the rat small intestine during hypothalamic monosodium glutamate (MSG)-induced obesity. The rats were divided into four groups: Sedentary (S), Monosodium Glutamate (MSG), Exercised (E), and Exercised Monosodium Glutamate (EMSG). The MSG and EMSG groups received a daily injection of monosodium glutamate (4 g/kg) during the 5 first days after birth. The S and E groups were considered as control groups and received injections of saline. At weaning, at 21 days after birth, the EMSG and E groups were submitted to swimming practice 3 times a week until the 90th day, when all groups were sacrificed and the parameters studied recorded. Exercise significantly reduced fat deposits and the Lee Index in MSG-treated animals, and also reduced the thickness of the intestinal wall, the number of goblet cells and intestinal alkaline phosphatase activity. However, physical activity alone increased the thickness and height of villi, and the depth of the crypts. In conclusion, regular physical exercise may alter the morphology or/and functions of the small intestine, reducing the prejudicial effects of hypothalamic obesity. Anat Rec, 299:1389-1396, 2016. © 2016 Wiley Periodicals, Inc.

  4. The effects of dietary saturated fat on basal hypothalamic neuroinflammation in rats.

    Science.gov (United States)

    Maric, Tia; Woodside, Barbara; Luheshi, Giamal N

    2014-02-01

    Recent evidence has demonstrated that consumption of high fat diets can trigger brain inflammation and subsequent injury in the absence of any peripheral inflammatory signaling. Here we sought to investigate whether a link exists between the concentration of highly saturated fats in the diet and the development of inflammation in the brain of rats and, whether the source of the saturated fat was an important factor in this process. Adult male rats had access to diets with a moderate level of total fat (32% of calories as fat) varying in level of saturated fat [low (20%) vs high (>60%)] and its source (butter or coconut oil). After 8 weeks of diet exposure peripheral and central tissues were collected for analysis of inflammatory signals. Neither blood nor white adipose tissue exhibited any changes in inflammatory mediators regardless of the saturated fat content or the source. In the brain however, we observed significant hypothalamic upregulation of the expression of markers of glial activation as well as of interleukin (IL)-1,6 and nuclear factor (NF)-IL-6, which were highest in the group fed the butter-based diets. The increase in these inflammatory mediators had no effect on basal body temperature or the temperature response to systemic lipopolysaccharide (LPS). The present results indicate that hypothalamic inflammation associated with consumption of diets high in fat is directly linked to the saturated fat content as well as the source of that fat. These effects are likely linked to other pathophysiological changes in the regulation of metabolism.

  5. 2-deoxy-D-glucose suppresses food intake through activation of hypothalamic histamine in rats.

    Science.gov (United States)

    Sakata, T; Tamari, Y; Kang, M; Yoshimatsu, H

    1994-08-01

    The aim of this experiment was to demonstrate whether brain histamine contributes to delayed suppression of food intake after administration of 2-deoxy-D-glucose (2-DG). Food intake decreased significantly for 48 h after infusion of 2-DG into the rat third cerebroventricle. This delayed decrease in food intake was abolished by depletion of neuronal histamine by intraperitoneal pretreatment with alpha-fluoromethylhistidine (160 mumol/rat), a suicide inhibitor of a histamine-synthesizing enzyme. Intracerebroventricular infusion of 24 mumol 2-DG accelerated turnover rate of hypothalamic histamine. These results indicate that the delayed feeding suppression by 2-DG is modulated through histaminergic neurons in the hypothalamus. This histaminergic response may be related, at least in part, to homeostatic control of energy metabolism in the brain.

  6. Neonatal Nicotine Exposure Leads to Hypothalamic Gliosis in Adult Overweight Rats.

    Science.gov (United States)

    Younes-Rapozo, V; Moura, E G; Manhães, A C; Pinheiro, C R; Carvalho, J C; Barradas, P C; de Oliveira, E; Lisboa, P C

    2015-12-01

    Astrocytes and microglia, the immune competent cells of central nercous system, can be activated in response to metabolic signals such as obesity and hyperleptinaemia. In rats, maternal exposure to nicotine during lactation leads to central obesity, hyperleptinaemia, leptin resistance and alterations in hypothalamic neuropeptides in the offspring during adulthood. In the present study, we studied the activation of astrocytes and microglia, as well as the pattern of inflammatory mediators, in adult offspring of this experimental model. On postnatal day 2 (P2), osmotic minipumps releasing nicotine (NIC) (-6 mg/kg/day) or saline for 14 days were s.c. implanted in dams. Male offspring were killed on P180 and hypothalamic immunohistochemistry, retroperitoneal white adipose tissue (WAT) polymerase chain reaction analysis and multiplex analysis for plasma inflammatory mediators were carried out. At P180, NIC astrocyte cell number was higher in the arcuate nucleus (ARC) (medial: +82%; lateral: +110%), in the paraventricular nucleus (PVN) (+144%) and in the lateral hypothalamus (+121%). NIC glial fibrillary acidic protein fibre density was higher in the lateral ARC (+178%) and in the PVN (+183%). Interleukin-6 was not affected in the hypothalamus. NIC monocyte chemotactic protein 1 was only higher in the periventricular nucleus (+287%). NIC microglia (iba-1-positive) cell number was higher (+68%) only in the PVN, as was the chemokine (C-X3-C motif) receptor 1 density (+93%). NIC interleukin-10 was lower in the WAT (-58%) and plasma (-50%). Thus, offspring of mothers exposed to nicotine during lactation present hypothalamic astrogliosis at adulthood and microgliosis in the PVN.

  7. Effects of cysteamine on the hypothalamic-pituitary axis in the rat

    Energy Technology Data Exchange (ETDEWEB)

    McComb, D.J.; Cairns, P.D.; Kovacs, K.; Szabo, S.

    1985-06-01

    The effects of cysteamine (CSH) on hypothalamic concentrations of neuropeptides were reviewed and correlated with available information on changes in pituitary hormone content and circulating pituitary hormone levels. In our study, we found notable changes in the morphology of lactotropes from female Long-Evans rats treated for 7 days with CSH (300 mg/(kg X day) per os). Forming granules increased in number, and crinophagy, which is the augmented incorporation of these granules into lysosomes, was evident. Storage granules were reduced in number. These changes were not suppressed by simultaneous administration of 17 beta-estradiol (50 micrograms/day s.c.) for 7 days. CSH administration failed to prevent estrogen-induced lactotrope hyperplasia. Serum prolactin levels were unaffected by CSH treatment. The morphological changes in the adenohypophysis did not resemble those observed when rats were treated with bromocriptine. The rough endoplasmic reticulum luminal density was reduced in gonadotropes from intact CSH-treated rats after 1 wk. CSH treatment suppressed the development of castration cells and significantly reduced serum luteinizing hormone levels in ovariectomized rats. The morphological effects of CSH appeared to be confined to lactotropes and gonadotropes.

  8. Changes in hypothalamic staining for c-Fos following 2G exposure in rats

    Science.gov (United States)

    Fuller, C. A.; Murakami, D. M.; Hoban-Higgins, T. M.; Tang, I. H.

    1994-01-01

    The static gravitational field of the earth has been an important selective pressure that has shaped the evolution of biological organisms. This is illustrated by the evolution of tetrapods from a water environment where gravitational force was partially negated to a terrestrial environment where gravity is of greater consequence. Terrestrial invasion resulted in a series of new structural, physiological, and behavioral features. Therefore, it is not surprising that alterations in the gravitational field can cause widespread effects in many physiological systems and behaviors. Our previous studies have demonstrated that both exposure to hyperdynamic fields and the microgravity condition of space flight have significant effects on body temperature, heartrate, activity, feeding, drinking, and circadian rhythms. However, it has not been determined whether these physiological adaptations are associated with changes in neural activity within the hypothalamic nuclei that regulate these functions. This study examined the changes in body temperature, activity, body weight and food and water intake in rats caused by exposure to a hyperdynamic field. In addition, the immediate early gene activation marker, c-Fos, was used to examine potential protein synthesis changes in the hypothalamic nuclei that regulate these functions.

  9. [Changes in the cholecystokinin-synthetizing hypothalamic system during experimental diabetes mellitus in rats].

    Science.gov (United States)

    Abramov, A V; Kolesnik, Iu M; Trzhetsinskiĭ, S D; Orlovskiĭ, M A

    1998-01-01

    The investigation was performed in 96 Wistar rats. Diabetes mellitus was induced by single injection of 50 mg/kg of streptozotocin. Cholecystokinin (CCK) synthesizing neurons were identified in hypothalamic structures using indirect immunofluorescence. In latent period of diabetes (2 wks) number of CCK--immunopositive neurons increases, especially in paraventricular and suprachiasmatic nuclei, while in ventrolateral subnucleus of arcuate nucleus and parvicellular subnucleus of paraventricular nucleus areas occupied by immunoreactive material in neurons and their CCK content are reduced. By the end of wk 5 of the disease increase in number of CCK immunopositive neurons was registered only in medial parvicellular subnucleus of paraventricular nucleus whereas in other structures their number was reduced. The administration of CCK to intact animals causes increase of insulin content in endocrinocytes of pancreatic islets, but does not affect the level of hypoglycemia. The administration of the peptide to animals with diabetes leads to destruction of pancreatic islets, decline in endocrinocyte number and insulin content and marked hypoglycemia. Thus, the data obtained indicate the significant role of hypothalamic peptidergic system and CCK in regulation of beta-endocrinocyte function.

  10. A quantification of the relationship between neuronal responses in the rat rostral ventromedial medulla and noxious stimulation-evoked withdrawal reflexes.

    Science.gov (United States)

    Devonshire, I M; Kwok, C H T; Suvik, A; Haywood, A R; Cooper, A H; Hathway, G J

    2015-07-01

    The rostral ventromedial medulla (RVM) regulates a range of involuntary behaviours but is most often associated with nociception via the action of pronociceptive ON cells and antinociceptive OFF cells. The phasic responses of ON and OFF cells determine whether or not incoming noxious signals provoke a withdrawal reflex, and previous studies have suggested that reflex RVM activity patterns actively shape motor output. Here we challenged the model by using juvenile rats, which are known to exhibit markedly different reflex responses compared with adults. By recording single-cell activity in the RVM and the electromyography responses of hindlimb flexor muscles to noxious thermal stimulation we found that the juvenile reflex had a shorter onset latency, was larger in amplitude and exhibited a decreased rise time compared with the adult reflex. The responses of ON and OFF cells faithfully tracked the shorter onset latency of the reflex by also responding earlier and, thus, still preceded the reflex. However, neither the reflex amplitude nor the ongoing response profile was predicted by the firing rate of RVM cells in either age group. Instead we found a close correspondence between RVM activity and the reflex only during the initiation of the response. Furthermore, the short rise time of the juvenile reflex was reflected in higher rates of change of both ON and OFF cell firing. Our data suggest that the RVM is associated only with the initiation of reflexes and does not shape ongoing muscle activity, which is more likely to be subserved by downstream spinal processes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. Hypothalamic kiss1 mRNA and kisspeptin immunoreactivity are reduced in a rat model of polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Brown, Russell E; Wilkinson, Diane A; Imran, Syed A; Caraty, Alain; Wilkinson, Michael

    2012-07-27

    An intact hypothalamic kiss1/kisspeptin/kiss1r complex is a prerequisite for reproductive competence, and kisspeptin treatment could be a practical therapeutic approach to some problems of infertility. One such disorder is polycystic ovarian syndrome (PCOS), a common cause of infertility affecting more than 100 million women. A rodent model of PCOS is the prepubertal female rat treated for a prolonged period with dihydrotestosterone (DHT), which induces many of the metabolic characteristics of the syndrome. We hypothesized that hypothalamic kiss1 mRNA levels, and kisspeptin immunoreactivity (ir), would be abnormal in these rats. Prepubertal female rats were exposed to DHT for 60 days. Rats were killed in two groups: at 26 and 60 days of DHT exposure. Kiss1 mRNA was quantified in hypothalamus, pituitary, ovary and visceral adipose tissue. Separate groups of rats provided brain tissue for immunohistochemical analysis of kisspeptin-ir. At 26 days of DHT exposure, hypothalamic kiss1 mRNA was severely depleted. In contrast DHT had no effect on pituitary kiss1 expression but it significantly increased levels of kiss1 mRNA in fat (+9-fold; povary (+3-fold; povary but remained elevated in fat (+4-fold; ppolycystic ovary syndrome. In hypothalamus, specifically, kiss1 mRNA, and levels of kisspeptin immunoreactivity, are significantly reduced. Since these rats exhibit many of the characteristics of polycystic ovary syndrome, we suggest that atypical kiss1 expression may contribute to the multiple tissue abnormalities observed in women with this disorder. However, and of some importance, our data do not appear to be consistent with the elevated levels of LH seen in women with PCOS; i.e. reduced levels of hypothalamic kiss1 mRNA and kisspeptin immunoreactivity observed in DHT-treated rats are unlikely to produce elevated LH secretion.

  12. Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism.

    Science.gov (United States)

    Andreoli, María Florencia; Stoker, Cora; Rossetti, María Florencia; Alzamendi, Ana; Castrogiovanni, Daniel; Luque, Enrique H; Ramos, Jorge Guillermo

    2015-02-05

    The absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis. Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance. Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. The role of the chorda tympani nerve in the activation of the rat hypothalamic histaminergic system by leptin.

    Science.gov (United States)

    Morimoto-Ishizuka, T; Yamamoto, Y; Yamatodani, A

    2001-03-01

    A possible pathway through which leptin activates the histaminergic system was studied using in vivo microdialysis in rats. Intraperitoneal injection of leptin (1.3 mg/kg) caused a significant increase in hypothalamic histamine release, however, its intracerebroventricular injection (10 microg/rat) did not cause any significant changes in the release. Furthermore, leptin (1.3 mg/kg) had no effect on histamine release in rats whose chorda tympani nerves, a branch of the facial nerve which mediates taste information, were transected bilaterally. These findings indicate that leptin activates the histaminergic system by the peripheral signal inputs via the chorda tympani resulting in the suppression of food intake.

  14. Intracisternally Injected L-Proline Activates Hypothalamic Supraoptic, but Not Paraventricular, Vasopressin-Expressing Neurons in Conscious Rats

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    Yumi Takemoto

    2011-01-01

    Full Text Available When injected into specific rat brain regions, the neurotransmitter candidate L-proline produces various cardiovascular changes through ionotropic excitatory amino acid receptors. The present study used an immunohistochemical double-labeling approach to determine whether intracisternally injected L-proline in freely moving rats, which increases blood pressure, activates hypothalamic vasopressin-expressing neurons and ventral medullary tyrosine-hydroxylase- (TH- containing neurons. Following injection of L-proline, the number of activated hypothalamic neurons that coexpressed vasopressin and c-Fos was much greater in the supraoptic nucleus (SON than in the paraventricular nucleus (PVN of rats with increased blood pressure. The number of activated TH-containing neurons was significantly greater following L-proline treatment than following control injections of artificial cerebrospinal fluid (ACSF. These results clearly demonstrate that intracisternally injected L-proline activates hypothalamic supraoptic, but not paraventricular, vasopressin-expressing neurons and medullary TH-containing (A1/C1 neurons in freely moving rats.

  15. Developmental changes in the hypothalamic mRNA levels of prepro-orexin and orexin receptors and their sensitivity to fasting in male and female rats.

    Science.gov (United States)

    Iwasa, Takeshi; Matsuzaki, Toshiya; Munkhzaya, Munkhsaikhan; Tungalagsuvd, Altankhuu; Kuwahara, Akira; Yasui, Toshiyuki; Irahara, Minoru

    2015-11-01

    Orexin, which is also called as hypocretin (Hcrt), a product of the prepro-orexin (pp-orexin//Hcrt) gene, affects various physiological and behavioral functions, such as the sleep-wake cycle and appetite. The developmental changes in the hypothalamic mRNA levels of pp-prexin and the orexin receptors OX1R and OX2R and their sensitivity to fasting were evaluated in both male and female rats. During development, hypothalamic pp-orexin/Hcrt mRNA expression increased in both male and female rats, whereas hypothalamic OX1R mRNA expression decreased in both sexes. In addition, hypothalamic OX2R mRNA expression increased in male rats, but did not change in female rats. Fasting did not affect hypothalamic pp-orexin/Hcrt mRNA expression in either sex. Hypothalamic OX1R mRNA expression was increased by fasting in the prepubertal period (postnatal days 20 and 30) in female rats, but was not affected by fasting in males. In male rats, hypothalamic OX2R mRNA expression was decreased by fasting during the neonatal period (postnatal day 10), but not the prepubertal period (postnatal days 20 and 30). In females, hypothalamic OX2R mRNA expression was also decreased by fasting; however, the fasting-induced downregulation of hypothalamic OX2R expression persisted until postnatal day 20. These results indicate that the developmental patterns of components of the orexin system and their sensitivity to fasting during the neonatal and prepubertal periods only differ slightly between the sexes. These differences might be involved in the development of some physiological and behavioral functions.

  16. Electrical stimulation of the ventromedial hypothalamus enhances both fat utilization and metabolic rate that precede and parallel the inhibition of feeding behavior

    NARCIS (Netherlands)

    Ruffin, MP; Nicolaidis, S

    1999-01-01

    The effects of ventromedial hypothalamic (VMH) stimulation on various metabolic parameters in freely moving animals were measured using a specific indirect calorimetric chamber associated with a quantitative measurement of locomotor activity, which allows the separate measurement of locomotor energy

  17. Electrical stimulation of the ventromedial hypothalamus enhances both fat utilization and metabolic rate that precede and parallel the inhibition of feeding behavior

    NARCIS (Netherlands)

    Ruffin, MP; Nicolaidis, S

    1999-01-01

    The effects of ventromedial hypothalamic (VMH) stimulation on various metabolic parameters in freely moving animals were measured using a specific indirect calorimetric chamber associated with a quantitative measurement of locomotor activity, which allows the separate measurement of locomotor energy

  18. Inflammatory airway features and hypothalamic-pituitary adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    CAI Cui; CAO Yu-xue; ZHANG Hong-ying; LE Jing-jing; DONG Jing-cheng; CUI Yan; XU Chang-qing; LIU Bao-jun; WU Jin-feng; DUAN Xiao-hong

    2010-01-01

    Background Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal (HPA) axis function in asthmatic rats combined with COPD.Methods Brown Norway (BN) rats were used to model the inflammatory airway diseases of BA, COPD and COPD+BA.These three models were compared and evaluated with respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness (AHR), inflammatory cytokines and HPA axis function.Results The inflammatory airway features and HPA axis function in rats in the COPD+BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group (P <0.05).Conclusions BN rat can be used as an animal model of COPD+BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.

  19. Maternal programming of sexual behavior and hypothalamic-pituitary-gonadal function in the female rat.

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    Nicole Cameron

    Full Text Available Variations in parental care predict the age of puberty, sexual activity in adolescence and the age at first pregnancy in humans. These findings parallel descriptions of maternal effects on phenotypic variation in reproductive function in other species. Despite the prevalence of such reports, little is known about potential biological mechanisms and this especially true for effects on female reproductive development. We examined the hypothesis that parental care might alter hypothalamic-pituitary-ovarian function and thus reproductive function in the female offspring of rat mothers that vary pup licking/grooming (LG over the first week postpartum. As adults, the female offspring of Low LG mothers showed 1 increased sexual receptivity; 2 increased plasma levels of luteinizing hormone (LH and progesterone at proestrus; 3 an increased positive-feedback effect of estradiol on both plasma LH levels and gonadotropin releasing-hormone (GnRH expression in the medial preoptic region; and 4 increased estrogen receptor alpha (ERalpha expression in the anterioventral paraventricular nucleus, a system that regulates GnRH. The results of a cross-fostering study provide evidence for a direct effect of postnatal maternal care as well as a possible prenatal influence. Indeed, we found evidence for increased fetal testosterone levels at embryonic day 20 in the female fetuses of High compared to Low LG mothers. Finally, the female offspring of Low LG mothers showed accelerated puberty compared to those of High LG mothers. These data suggest maternal effects in the rat on the development of neuroendocrine systems that regulate female sexual behaviour. Together with studies revealing a maternal effect on the maternal behavior of the female offspring, these findings suggest that maternal care can program alternative reproductive phenotypes in the rat through regionally-specific effects on ERalpha expression.

  20. Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.

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    Benjamin Jurek

    Full Text Available The c-Raf - MEK1/2 - ERK1/2 mitogen-activated protein kinase (MAPK intracellular signalling cascade in neurons plays important roles in the control of a variety of behaviours, including social behaviours and anxiety. These roles partially overlap with those described for oxytocin (OXT, and it has been shown that OXT activates the MAPK pathway in the hypothalamus (of male, and hippocampus (of female rats. Here, by combining behavioural (light/dark box and biochemical analyses (western blotting, we tested two hypotheses: (i that OXT is anxiolytic within the hypothalamus of females, and (ii that this effect, as well as that of lactation-associated anxiolysis, depends on the recruitment of the MAPK pathway. We found that, when injected bilaterally into the hypothalamic paraventricular nucleus (PVN, OXT decreased anxiety-like behaviour in virgins, and that this effect depended on phosphorylation of MEK1/2. MAPK pathway activation in lactation was evident by high phosphorylated (p MEK1/2 levels, and nuclear translocation of ERK1. The high pMEK1/2 levels were necessary for the anxiolytic phenotype typically observed during lactation. Interestingly, exogenous OXT in lactating rats reduced pMEK1/2 levels without a concomitant effect on anxiety, indicating that OXT receptor activation can lead to recruitment of additional intracellular pathways to modulate MEK activity. Still other pathways could include MEK, but without subsequent activation of ERK, as we did not observe any increase in OXT-induced ERK phosphorylation. Together the results demonstrate that the MAPK pathway, especially MEK1/2, is critically involved in the regulation of anxiety-like behaviour in female rats.

  1. Circadian and estral changes in the hypothalamic prostaglandin e content and [h]prostaglandin e binding in female rats.

    Science.gov (United States)

    Bommelaer-Bayet, M C; Wisner, A; Renard, C A; Levi, F A; Dray, F

    1990-04-01

    Abstract Prostaglandin E(2), (PGE(2)) is involved in the luteinizing hormone-releasing hormone-stimulated luteinizing hormone surge in female rats and may act via specific membrane receptors. The following studies were performed to determine whether there were any changes in the hypothalamic PGE(2) binding and/or PGE(2) content which were specific to proestrus and not to the rest of the estrous cycle. Groups of female Wistar rats were sacrificed at 3-h intervals throughout the estrous cycle to determine both the circadian and circaestral changes in the hypothalamic PGE(2) content and [(3)H]PGE(2) binding. The hypothalamic PGE(2) content was maximal at 1700 h on each of the 4 consecutive days of the estrous cycle but was independent of the stage of the cycle. [(3)H]PGE(2) binding also displayed a circadian rhythm; the lowest binding occurred near the circadian peak of PGE(2), suggesting that the PGE(2) binding sites were occupied by endogenous PGE(2). Since such circadian rhythms were not observed in the hypothalamus of male rats, they may be under the control of ovarian steroids. Also, since PGE(2) binding and the PGE(2) content both exhibit a diurnal pattern independent of the day of the cycle, there may be changes in the PGE(2) receptor-mediated process coupled to an adenylyl cyclase which could explain the luteinizing hormone surge in proestrus.

  2. Hypothalamic galanin and plasma leptin and ghrelin in the maintenance of energy intake in the Brattleboro rat.

    Science.gov (United States)

    Beck, Bernard; Max, Jean-Pierre

    2007-12-07

    Galanin, ghrelin, and leptin are three peptides involved in feeding regulation and more particularly in fat intake. The Brattleboro (di/di) rat is a genetic model of diabetes insipidus characterized by a preference for fat when it is in a food choice situation. Here, we measured hypothalamic galanin concentrations, plasma ghrelin and leptin and dietary preferences of adult di/di Brattleboro rats, di/+ and Long-Evans controls. The Brattleboro rats weighed significantly less than the di/+ rats (-18%; Pdiet and a high-carbohydrate diet. Galanin concentrations were significantly lower in di/di rats than in di/+ rats in the paraventricular nucleus (-56%; P<0.001), but not in the arcuate nucleus. Plasma leptin was significantly lower in the di/di rats than in the di/+ rats (3.49+/-0.20 vs. 6.94+/-0.49 ng/ml; P<0.001). Plasma ghrelin concentrations were significantly lower in Long-Evans rats than in the di/di rats (-21%; P< 0.01). Given that galanin mRNA is overexpressed in the paraventricular nucleus of Brattleboro rats, these data are consistent with increased release of the peptide. In the Brattleboro rat, this overactive galanin system and the variations of ghrelin and leptin maintain an orexigenic drive favoring a preferential intake of fat which provides the animal with enough energy for its metabolism.

  3. Intrahypothalamic corticotropin-releasing factor elevates gastric bicarbonate and inhibits stress ulcers in rats.

    Science.gov (United States)

    Gunion, M W; Kauffman, G L; Taché, Y

    1990-01-01

    The effects of intrahyopthalamic microinfusions of corticotropin-releasing factor (CRF) on gastric bicarbonate, acid, and pepsin content and on cold restraint-induced gastric lesion formation were tested in three experiments. Bilateral microinfusions of CRF into the hypothalamic ventromedial nucleus (0.86 nmol/rat) significantly increased both gastric bicarbonate concentration and total bicarbonate output. These effects were observed irrespective of whether rats were pretreated with the acid antisecretory drug omeprazole. In nonomeprazole-pretreated rats, CRF microinfusions also significantly reduced acid secretion and raised pH. The increase in bicarbonate content accounted for half of the observed decrease in acid output, suggesting that CRF microinfusions activated separable bicarbonate-stimulating and acid-inhibiting hypothalamic systems. In non-omeprazole-pretreated rats, CRF microinfusions significantly increased serum gastrin, whereas pepsin output was unchanged. Gastric mucosal damage produced by 4 h of cold restraint was significantly diminished by CRF microinfusion into the ventromedial hypothalamus. These data demonstrate that ventromedial hypothalamic microinfusions of CRF increase bicarbonate content, decrease gastric acid content, and confer protection against cold restraint-induced gastric mucosal damage. Hypothalamic CRF neuronal terminals and receptors may be involved in the central regulation of gastric bicarbonate secretion as well as acid secretion.

  4. [Senescence of endocrine function with special reference to the hypothalamic-pituitary-gonadal axis in the rat (author's transl)].

    Science.gov (United States)

    Kawashima, S

    1977-12-20

    In the control theories, aging is under genetic and environmental control. Endocrine function plays an important role in this control system by mediating between the environmental influence and the presumptive "aging gene". Therefore, the intrinsic aging of the hypothalamus, such as the changes in sensitivity to feedback suppression or stimulation, may lead to homostatic failure and then age-related pathology. As the subject of study we have selected the senile changes in the hypothalamic-pituitary-ovarian axis in the rat of the Wistar strain. The cessation of estrous cycle and the onset of persistent estrus or repetitive pseudopregnancy usually take place as early as at the end of the first half of life in rats. In this paper the results of the following experiments are briefly dealt with: (i) reciprocal transplantation of ovaries between young and old rats (the term "old" designates here "incapable of reproduction"), (ii) comparison of LH and FSH binding abilities in the ovarian preparations, (iii) comparison of serum and pituitary concentrations of LH, FSH and prolactin and the modifications after ovariectomy or by the administration of pharmacological drugs, and (iv) the difference between young and old rats in intensity of dopamine fluorescence in the hypothalamus. The results of these experiments seem to point to the hypothalamic-pituitary part rather than more peripheral organs (ovaries) as being primarily responsible for the outcome of the senile changes in the female rat.

  5. A novel pathway regulates thyroid hormone availability in rat and human hypothalamic neurosecretory neurons.

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    Imre Kalló

    Full Text Available Hypothalamic neurosecretory systems are fundamental regulatory circuits influenced by thyroid hormone. Monocarboxylate-transporter-8 (MCT8-mediated uptake of thyroid hormone followed by type 3 deiodinase (D3-catalyzed inactivation represent limiting regulatory factors of neuronal T3 availability. In the present study we addressed the localization and subcellular distribution of D3 and MCT8 in neurosecretory neurons and addressed D3 function in their axons. Intense D3-immunoreactivity was observed in axon varicosities in the external zone of the rat median eminence and the neurohaemal zone of the human infundibulum containing axon terminals of hypophysiotropic parvocellular neurons. Immuno-electronmicroscopy localized D3 to dense-core vesicles in hypophysiotropic axon varicosities. N-STORM-superresolution-microscopy detected the active center containing C-terminus of D3 at the outer surface of these organelles. Double-labeling immunofluorescent confocal microscopy revealed that D3 is present in the majority of GnRH, CRH and GHRH axons but only in a minority of TRH axons, while absent from somatostatin-containing neurons. Bimolecular-Fluorescence-Complementation identified D3 homodimers, a prerequisite for D3 activity, in processes of GT1-7 cells. Furthermore, T3-inducible D3 catalytic activity was detected in the rat median eminence. Triple-labeling immunofluorescence and immuno-electronmicroscopy revealed the presence of MCT8 on the surface of the vast majority of all types of hypophysiotropic terminals. The presence of MCT8 was also demonstrated on the axon terminals in the neurohaemal zone of the human infundibulum. The unexpected role of hypophysiotropic axons in fine-tuned regulation of T3 availability in these cells via MCT8-mediated transport and D3-catalyzed inactivation may represent a novel regulatory core mechanism for metabolism, growth, stress and reproduction in rodents and humans.

  6. The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones

    Science.gov (United States)

    Bing, Chen; King, Peter; Pickavance, Lucy; Brown, Michael; Ziegler, Dieter; Kaan, Elbert; Williams, Gareth

    1999-01-01

    The antihypertensive agent moxonidine, an imidazoline Ii-receptor agonist, also induces hypophagia and lowers body weight in the obese spontaneously hypertensive rat, but the central mediation of this action and the neuronal pathways that moxonidine may interact with are not known. We studied whether moxonidine has anti-obesity effects in the genetically-obese and insulin-resistant fa/fa Zucker rat, and whether these are mediated through inhibition of the hypothalamic neuropeptide Y (NPY) neurones.Lean and obese Zucker rats were given moxonidine (3 mg kg−1 day−1) or saline by gavage for 21 days.Moxonidine decreased food intake throughout by 20% in obese rats (P<0.001) and by 8% in lean rats (P<0.001), and reduced weight gain that final body weight was 15% lower in obese (P<0.001) and 7% lower in lean (P<0.01) rats than their untreated controls. Plasma insulin and leptin levels were decreased in moxonidine-treated obese rats (P<0.01 and P<0.05), but unchanged in treated lean rats. Uncoupling protein-1 gene expression in brown adipose tissue was stimulated by 40–50% (P⩽0.05) in both obese and lean animals given moxonidine. Obese animals given moxonidine showed a 37% reduction in hypothalamic NPY mRNA levels (P=0.01), together with significantly increased NPY concentrations in the paraventricular nucleus (P<0.05), but no changes in the arcuate nucleus or other nuclei; this is consistent with reduced NPY synthesis in the arcuate nucleus and blocked release of NPY in the paraventricular nucleus. In lean animals, moxonidine did not affect NPY levels or NPY mRNA.The hypophagic, thermogenic and anti-obesity effects of moxonidine in obese Zucker rats may be partly due to inhibition of the NPY neurones, whose inappropriate overactivity may underlie obesity in this model. PMID:10369453

  7. Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats.

    Science.gov (United States)

    Stern, Javier E; Sonner, Patrick M; Son, Sook Jin; Silva, Fabiana C P; Jackson, Keshia; Michelini, Lisete C

    2012-05-01

    Elevated sympathetic outflow and altered autonomic reflexes, including impaired baroreflex function, are common findings observed in hypertensive disorders. Although a growing body of evidence supports a contribution of preautonomic neurons in the hypothalamic paraventricular nucleus (PVN) to altered autonomic control during hypertension, the precise underlying mechanisms remain unknown. Here, we aimed to determine whether the intrinsic excitability and repetitive firing properties of preautonomic PVN neurons that innervate the nucleus tractus solitarii (PVN-NTS neurons) were altered in spontaneously hypertensive rats (SHR). Moreover, given that exercise training is known to improve and/or correct autonomic deficits in hypertensive conditions, we evaluated whether exercise is an efficient behavioral approach to correct altered neuronal excitability in hypertensive rats. Patch-clamp recordings were obtained from retrogradely labeled PVN-NTS neurons in hypothalamic slices obtained from sedentary (S) and trained (T) Wistar-Kyoto (WKY) and SHR rats. Our results indicate an increased excitability of PVN-NTS neurons in SHR-S rats, reflected by an enhanced input-output function in response to depolarizing stimuli, a hyperpolarizing shift in Na(+) spike threshold, and smaller hyperpolarizing afterpotentials. Importantly, we found exercise training in SHR rats to restore all these parameters back to those levels observed in WKY-S rats. In several cases, exercise evoked opposing effects in WKY-S rats compared with SHR-S rats, suggesting that exercise effects on PVN-NTS neurons are state dependent. Taken together, our results suggest that elevated preautonomic PVN-NTS neuronal excitability may contribute to altered autonomic control in SHR rats and that exercise training efficiently corrects these abnormalities.

  8. Stress and Sucrose Intake Modulate Neuronal Activity in the Anterior Hypothalamic Area in Rats

    Science.gov (United States)

    Mitra, Arojit; Guèvremont, Geneviève; Timofeeva, Elena

    2016-01-01

    The anterior hypothalamic area (AHA) is an important integrative relay structure for a variety of autonomic, endocrine, and behavioral responses including feeding behavior and response to stress. However, changes in the activity of the AHA neurons during stress and feeding in freely moving rats are not clear. The present study investigated the firing rate and burst activity of neurons in the central nucleus of the AHA (cAHA) during sucrose intake in non-stressful conditions and after acute stress in freely behaving rats. Rats were implanted with micro-electrodes into the cAHA, and extracellular multi-unit activity was recorded during 1-h access to 10% sucrose in non-stressful conditions or after acute foot shock stress. Acute stress significantly reduced sucrose intake, total sucrose lick number, and lick frequency in licking clusters, and increased inter-lick intervals. At the cluster start (CS) of sucrose licking, the cAHA neurons increased (CS-excited, 20% of the recorded neurons), decreased (CS-inhibited, 42% of the neurons) or did not change (CS-nonresponsive, 38% of the neurons) their firing rate. Stress resulted in a significant increase in the firing rate of the CS-inhibited neurons by decreasing inter-spike intervals within the burst firing of these neurons. This increase in the stress-induced firing rate of the CS-inhibited neurons was accompanied by a disruption of the correlation between the firing rate of CS-inhibited and CS-nonresponsive neurons that was observed in non-stressful conditions. Stress did not affect the firing rate of the CS-excited and CS-nonresponsive neurons. However, stress changed the pattern of burst firing of the CS-excited and CS-nonresponsive neurons by decreasing and increasing the burst number in the CS-excited and CS-nonresponsive neurons, respectively. These results suggest that the cAHA neurons integrate the signals related to stress and intake of palatable food and play a role in the stress- and eating-related circuitry

  9. A COMPARATIVE STUDY ON HYPOTHALAMIC MECHANISMS OF ANALGESIA INDUCED BY FOUR KINDS OF ACUPUNCTURE THERAPIES IN ADJUVANT ARTHRITIS RATS

    Institute of Scientific and Technical Information of China (English)

    FU Yi; LIANG Fan-rong; TAO Qiao-lin

    2005-01-01

    Objective: To compare the mechanisms of analgesia induced by four kinds of acupuncture therapies at the hypothalamic level in adjuvant arthritic rats. Methods: Forty-eight SD rats were randomized into normal, model, electroacupuncture (EA), filiform needle (FN), pricking blood-letting (BL) and point injection (PI) groups, with 8 cases in each. EA (20-100 Hz, 2-4 V and duration of 20 min), FN, BL PI were respectively applied to "Kunlun" (昆仑BL 60). Arthritis model was established by injecting complete Freund's adjuvant (0.1 mL) into the rat's right foot pad. Behavioral reactions, pain threshold (latency of tail flick to heat stimulation) and local swelling severity (foot volume) were detected; the contents of β-endorphin (β-EP) and adrenocorticotropin (ACTH) were assayed with radioimmunoassay; and the expression of pro-opi-omelanocortin (POMC) mRNA in hypothalamus were determined with hybridization method. Results: The pain threshold was significantly enhanced by all the four kinds of acupuncture therapies, and the effects of EA and PI were more obvious (P0.05). The content of β-EP in the hypothalamus was obviously elevated by EA and FN (P0.05). The content of ACTH in hypothalamus was considerably elevated by PI (P<0.05), but not by the other three therapies. The expression of POMCmRNA in hypothalamus was significantly strengthened by EA and FN (P<0.01), but not by the other two therapies. Conclusion: EA, filiform needle, blood-letting and point-injection all can produce analgesic effect in adjuvant arthritis rats, the effect of EA and filiform needle may be related to their resultant increase of hypothalamic β-EP, and that of point-injection related to the increase of hypothalamic ACTH level.

  10. Plasma CRH response to water immersion-restraint stress in rats bearing a hypothalamic knife cut.

    Science.gov (United States)

    Nishioka, T; Iyota, K; Takao, T; Suemaru, S; Numata, Y; Hashimoto, K

    1994-08-01

    We reported earlier that the plasma level of corticotropin-releasing hormone (CRH) remained high 120 min after the onset of such strong sustained stress as ether-laparotomy or water immersion-restraint, which reflected the persistent secretion of CRH from the hypothalamic median eminence (ME). We investigated the change in plasma CRH during water immersion-restraint stress in rats bearing an anterolateral cut around the medial basal hypothalamus (MBH) which cuts the CRH neurons from the PVN to the ME. Concentrations of CRH in the hypothalamus, extrahypothalamic tissues and peripheral blood were measured by radioimmunoassay. Plasma ACTH was measured with an immunoradiometric assay kit. Plasma baseline ACTH and CRH concentrations did not differ significantly in the sham vs. cut groups. At 120 min after the onset of stress, plasma ACTH concentrations were definitely higher in both groups. In the cut group, plasma CRH at 120 min after stress did not differ significantly from the baseline level, whereas plasma CRH at 120 min was definitely higher in the sham group. Baseline CRH concentrations in the ME did not differ greatly in the two groups. CRH concentrations in the ME of both groups had decreased appreciably 120 min after the onset of stress as compared with baseline CRH, and the CRH decrease was greater in the cut group than in the sham group. CRH in the neurointermediate lobe (NIL) and adrenal gland of both groups showed no significant change at 120 min, compared with the control. These findings confirm that the continuous CRH increase in plasma during sustained stress is derived mainly from the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. A Thalamo-Hypothalamic Pathway That Activates Oxytocin Neurons in Social Contexts in Female Rats.

    Science.gov (United States)

    Cservenák, Melinda; Keller, Dávid; Kis, Viktor; Fazekas, Emese A; Öllös, Hanna; Lékó, András H; Szabó, Éva R; Renner, Éva; Usdin, Ted B; Palkovits, Miklós; Dobolyi, Árpád

    2017-02-01

    Oxytocin is released from neurons in the paraventricular hypothalamic nucleus (PVN) in mothers upon suckling and during adult social interactions. However, neuronal pathways that activate oxytocin neurons in social contexts are not yet established. Neurons in the posterior intralaminar complex of the thalamus (PIL), which contain tuberoinfundibular peptide 39 (TIP39) and are activated by pup exposure in lactating mothers, provide a candidate projection. Innervation of oxytocin neurons by TIP39 neurons was examined by double labeling in combination with electron microscopy and retrograde tract-tracing. Potential classic neurotransmitters in TIP39 neurons were investigated by in situ hybridization histochemistry. Neurons activated after encounter with a familiar conspecific female in a familiar environment were mapped with the c-Fos technique. PVN and the supraoptic nucleus oxytocin neurons were closely apposed by an average of 2.0 and 0.4 TIP39 terminals, respectively. Asymmetric (presumed excitatory) synapses were found between TIP39 terminals and cell bodies of oxytocin neurons. In lactating rats, PIL TIP39 neurons were retrogradely labeled from the PVN. TIP39 neurons expressed vesicular glutamate transporter 2 but not glutamic acid decarboxylase 67. PIL contained a markedly increased number of c-Fos-positive neurons in response to social encounter with a familiar conspecific female. Furthermore, the PIL received ascending input from the spinal cord and the inferior colliculus. Thus, TIP39 neurons in the PIL may receive sensory input in response to social interactions and project to the PVN to innervate and excite oxytocin neurons, suggesting that the PIL-PVN projection contributes to the activation of oxytocin neurons in social contexts. Copyright © 2017 by the Endocrine Society.

  12. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    OpenAIRE

    Hojatollah Karimi Jashni; Hossein Kargar Jahromi; Ali Ghorbani Ranjbary

    2016-01-01

    Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses ...

  13. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    OpenAIRE

    Karimi Jashni, Hojatollah; Kargar Jahromi, Hossein; Ghorbani Ranjbary, Ali; Kargar Jahromi, Zahra; Khabbaz Kherameh, Zahra

    2016-01-01

    Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, ...

  14. Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction?

    Directory of Open Access Journals (Sweden)

    Carlo eCifani

    2015-06-01

    Full Text Available Several factors play a role in obesity (i.e. behavior, environment, and genetics and epigenetic regulation of gene expression has emerged as a potential contributor in the susceptibility and development of obesity. To investigate the individual sensitivity to weight gain/resistance, we here studied gene transcription regulation of several hypothalamic neuropeptides involved in the control of energy balance in rats developing obesity (diet-induced obesity, DIO or not (diet resistant, DR, when fed with a high fat diet. Rats have been followed up to 21 weeks of high fat diet exposure. After 5 weeks high fat diet exposure, the obese phenotype was developed and we observed a selective down-regulation of the orexygenic neuropeptide Y (NPY and peroxisome proliferator-activated receptor gamma (PPAR-γ genes. No changes were observed in the expression of the agouti-related protein (AgRP, as well as for all the anorexigenic genes under study. After long-term high fat diet exposure (21 weeks, NPY and PPAR-γ, as well as most of the genes under study, resulted not be different between DIO and DR, whereas a lower expression of the anorexigenic pro-opio-melanocortin (POMC gene was observed in DIO rats when compared to DR rats. Moreover we observed that changes in NPY and POMC mRNA were inversely correlated with gene promoters DNA methylation. Our findings suggest that selective alterations in hypothalamic peptide genes regulation could contribute to the development of overweight in rats and that environmental factor, as in this animal model, might be partially responsible of these changes via epigenetic mechanism.

  15. Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction?

    Science.gov (United States)

    Cifani, Carlo; Micioni Di Bonaventura, Maria V; Pucci, Mariangela; Giusepponi, Maria E; Romano, Adele; Di Francesco, Andrea; Maccarrone, Mauro; D'Addario, Claudio

    2015-01-01

    Several factors play a role in obesity (i.e., behavior, environment, and genetics) and epigenetic regulation of gene expression has emerged as a potential contributor in the susceptibility and development of obesity. To investigate the individual sensitivity to weight gain/resistance, we here studied gene transcription regulation of several hypothalamic neuropeptides involved in the control of energy balance in rats developing obesity (diet-induced obesity, DIO) or not (diet resistant, DR), when fed with a high fat diet. Rats have been followed up to 21 weeks of high fat diet exposure. After 5 weeks high fat diet exposure, the obese phenotype was developed and we observed a selective down-regulation of the orexigenic neuropeptide Y (NPY) and peroxisome proliferator-activated receptor gamma (PPAR-γ) genes. No changes were observed in the expression of the agouti-related protein (AgRP), as well as for all the anorexigenic genes under study. After long-term high fat diet exposure (21 weeks), NPY and PPAR-γ, as well as most of the genes under study, resulted not be different between DIO and DR, whereas a lower expression of the anorexigenic pro-opio-melanocortin (POMC) gene was observed in DIO rats when compared to DR rats. Moreover we observed that changes in NPY and POMC mRNA were inversely correlated with gene promoters DNA methylation. Our findings suggest that selective alterations in hypothalamic peptide genes regulation could contribute to the development of overweight in rats and that environmental factor, as in this animal model, might be partially responsible of these changes via epigenetic mechanism.

  16. Effect of estrogen agonists and antagonists on induction of progesterone receptor in a rat hypothalamic cell line.

    Science.gov (United States)

    Fitzpatrick, S L; Berrodin, T J; Jenkins, S F; Sindoni, D M; Deecher, D C; Frail, D E

    1999-09-01

    Estrogen is essential in the hypothalamus for the central regulation of reproduction. To understand the molecular mechanism(s) of estrogen action in the hypothalamus, immortalized rat embryonic hypothalamic cell lines were characterized for steroid receptors and subcloned. Scatchard analysis of the D12 subclone demonstrated one high affinity estrogen receptor-binding site (Kd = 31.3+/-1.9 pM) with a Bmax of 30.8+/-0.8 fmol/mg. Estrogen receptor-alpha protein was identified by Western blot and gel shift analyses. Treatment with estradiol (48 h) stimulated progesterone receptor (PR) messenger RNA expression and binding to [3H]R5020, a synthetic progestin. Because the agonist or antagonist activity of estrogen mimetics can be cell type dependent, the activities of various estrogen mimetics were determined in D12 cells. ICI 182,780 (IC50 = 0.63 nM), raloxifene (IC50 = 1 nM), enclomiphene (IC50 = 77 nM), and tamoxifen (IC50 = 174 nM) inhibited the induction of PR by estradiol, and none of these compounds significantly stimulated PR when given alone. In contrast, 17alpha-ethynyl estradiol (EC50 = 0.014 nM), zuclomiphene (EC50 = 100 nM), and genistein (EC50 = 17.5 nM) functioned as estrogen agonists in these cells. In addition, the estrogen-induced progesterone receptor activated a progesterone response element reporter construct in response to progestins. Thus, the D12 rat hypothalamic cell line provides a useful model for characterizing tissue-selective estrogenic compounds, identifying estrogen- and progesterone-regulated hypothalamic genes, and understanding the molecular mechanisms of steroid action in various physiological processes mediated by the hypothalamus.

  17. Regional haemodynamic effects of carbachol injected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats.

    Science.gov (United States)

    Bachelard, H; Gardiner, S M; Kemp, P A; Bennett, T

    1994-06-01

    Carbachol was injected into the hypothalamic paraventricular nuclei (PVN) of conscious, unrestrained Long Evans rats, chronically instrumented with intravascular catheters and pulsed Doppler probes to assess changes in regional haemodynamics. Bilateral microinjections of carbachol (1 ng-1 microgram) produced increases in blood pressure, bradycardias and vasoconstrictions in renal, superior mesenteric and hindquarters vascular beds. In the presence of phentolamine, the bradycardic and hindquarters vasoconstrictor responses to carbachol were unchanged while the pressor response was smaller due to a reduction in the renal and the superior mesenteric vasoconstriction. In the presence of propranolol, the bradycardic response was reduced, but the pressor and renal vasoconstrictor responses were potentiated, whereas the superior mesenteric and hindquarter vasoconstrictions were not changed significantly. In the presence of phentolamine and propranolol, the heart rate and pressor responses, as well as the renal vasoconstriction, were unchanged, whereas the superior mesenteric vasoconstriction was reduced and the hindquarters vasoconstriction was potentiated. Together these results are consistent with an involvement of the sympathoadrenal system in the pressor response to carbachol injected into the PVN of untreated animals. They indicate that alpha-adrenoceptor-mediated vasoconstriction in the superior mesenteric vascular bed is a particularly important component in that regard. In the presence of the vasopressin antagonist, d(CH2)5(Tyr(Et))DAVP, alone or in combination with phentolamine and propranolol, the pressor response to carbachol was substantially reduced, while the renal and superior mesenteric vasoconstrictor effects were completely abolished; the bradycardia was not significantly affected by this treatment. These results indicate an important involvement of vasopressin in the cardiovascular responses to carbachol injected into the PVN of untreated animals

  18. Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink

    Science.gov (United States)

    Kjaergaard, M; Nilsson, C; Secher, A; Kildegaard, J; Skovgaard, T; Nielsen, M O; Grove, K; Raun, K

    2017-01-01

    Background/objective: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. Methods: Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. Results: As expected, adult offspring fed the S diet post weaning became obese (body weight: Pdifferential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Conclusions: Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling. PMID:28092346

  19. Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink

    DEFF Research Database (Denmark)

    Gerstenberg, Marina Kjærgaard; Nilsson, C; Secher, A

    2017-01-01

    Background/objective: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic...... astrocyte morphology in adult rat offspring. Methods: Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were...... than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Conclusions: Maternal intake of chocolate and soft drink had long-term consequences...

  20. Exercise in rats does not alter hypothalamic AMP-activated protein kinase activity

    DEFF Research Database (Denmark)

    Andersson, Ulrika; Treebak, Jonas Thue; Nielsen, Jakob Nis

    2005-01-01

    or ran for 30 or 60 min on a treadmill (22 m/min, 10% slope) were sacrificed immediately after exercise or after 60 min recovery either in the fasted state or after oral gavage with glucose (3 g/kg body weight). Exercise decreased muscle and liver glycogen substantially. Hypothalamic total or a2...

  1. Programming of hypothalamic energy balance gene expression in rats by maternal diet during pregnancy and lactation

    National Research Council Canada - National Science Library

    Cripps, R. L; Martin-Gronert, M. S; Archer, Z. A; Hales, C. N; Mercer, J. G; Ozanne, S. E

    2009-01-01

    .... Expression of hypothalamic energy balance genes was assessed using in situ hybridisation. Recuperated pups were smaller at birth, but caught up with controls by day 21 and gained more weight than controls between weaning and 12 weeks of age (p<0.05...

  2. The total flavonoids extracted from Xiaobuxin Tang reverse the hyperactivity of hypothalamic-pituitary-adrenal axis in chronically stressed rats

    Institute of Scientific and Technical Information of China (English)

    AN Lei; ZHANG You-zhi

    2008-01-01

    Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal (HPA) axis in chronic mild stress (CMS) model of rats. Methods Using ELISA to test the serum corticos-terone, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) level in CMS rats; Using western blot to determine hippocampal glucocorticoids receptors (GR) expression in CMS rats. Results Co-administration of XBXT-2 (25, 50 mg·kg-1, p. o., 28 days, the effective doses for behavioral responses) significantly decreased the serum corticosterone and ACTH level in CMS rats, while the CRH level was not markedly affected by chronic stress or drugs. Moreover, XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats. The same effects were observed in the positive control drug imipramine ( 10 mg·kg-1 p. o. ). Conclusions The decrease of serum corticosterone and ACTH level, as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2, which may associate with HPA axis.

  3. Intravenous beta-endorphin administration fails to alter hypothalamic blood flow in rats expressing normal or reduced nitric oxide synthase activity

    NARCIS (Netherlands)

    Benyo, Z.; Szabo, C; Velkel, M.H; Bohus, B.G J; Wahl, M.A; Sandor, P

    1996-01-01

    beta-Endorphin (beta-END) significantly contributes to the maintenance of hypothalamic blood flow (HBF) autoregulation during hemorrhagic hypotension in rats. Recently, several natural and synthetic opioid peptides were reported to induce nitric oxide (NO)-mediated dilation in the cerebrovascular

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

    Directory of Open Access Journals (Sweden)

    Lígia Sousa-Ferreira

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

  5. Early postnatal amylin treatment enhances hypothalamic leptin signaling and neural development in the selectively bred diet-induced obese rat.

    Science.gov (United States)

    Johnson, Miranda D; Bouret, Sebastien G; Dunn-Meynell, Ambrose A; Boyle, Christina N; Lutz, Thomas A; Levin, Barry E

    2016-12-01

    Selectively bred diet-induced obese (DIO) rats become obese on a high-fat diet and are leptin resistant before becoming obese. Compared with diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y/agouti-related peptide (NPY/AgRP) and α-melanocyte-stimulating hormone (α-MSH; from proopiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC but not NPY/AgRP neurons. Since amylin increases leptin signaling in adult rats, we treated DIO neonates with amylin during postnatal hypothalamic development and assessed leptin signaling, leptin-dependent ARC-PVN pathway development, and metabolic changes. DIO neonates treated with amylin from P0-6 and from P0-16 increased ARC leptin signaling and both AgRP and α-MSH ARC-PVN pathway development, but increased only POMC neuron number. Despite ARC-PVN pathway correction, P0-16 amylin-induced reductions in body weight did not persist beyond treatment cessation. Since amylin enhances adult DIO ARC signaling via an IL-6-dependent mechanism, we assessed ARC-PVN pathway competency in IL-6 knockout mice and found that the AgRP, but not the α-MSH, ARC-PVN pathway was reduced. These results suggest that both leptin and amylin are important neurotrophic factors for the postnatal development of the ARC-PVN pathway. Amylin might act as a direct neurotrophic factor in DIO rats to enhance both the number of POMC neurons and their α-MSH ARC-PVN pathway development. This suggests important and selective roles for amylin during ARC hypothalamic development.

  6. The role of the hypothalamic nitric oxide in the pressor responses elicited by acute environmental stress in awake rats.

    Science.gov (United States)

    Kawa, T; Takeda, K; Harada, S; Hatta, T; Moriguchi, J; Miki, S; Morimoto, S; Itoh, H; Nakata, T; Sasaki, S; Nakagawa, M

    2002-08-09

    We quantitatively investigated the change in nitric oxide (NO) in the hypothalamic paraventricular nucleus (PVN) and its effect on cardiovascular regulation during shaker stress (SS) using brain microdialysis in awake rats. Male Wistar rats were fed either N(G)-nitro-L-arginine methyl ester (L-NAME, 0.7 g/L) or tap water for 2 weeks. Two days after implantation of an arterial catheter and guide shaft, a microdialysis probe was placed to perfuse the PVN with degassed Ringer solution at 2 microl/min in awake normotensive Wistar (CONTROL) and chronic L-NAME-treated hypertensive rats. After the rat was placed in a plastic cage set on a shaker, the blood pressure and heart rate was monitored and 10-min SS was loaded at a frequency of 200 cycles/min. Dialysate samples were analyzed by NO analyzer (based on the Griess reaction) every 10 min, and NOx (NO(2)(-) + NO(3)(-)) was measured. Plasma NOx was also measured before and after SS. Pressor responses elicited by SS were significantly greater in L-NAME-treated rats than in the CONTROL. Although NOx in the PVN dialysate were increased by SS in the CONTROL, these responses were attenuated in chronic L-NAME-treated rats. Resting plasma NOx were higher in the CONTROL than in L-NAME-treated rats. SS elicited no difference between two groups in plasma NOx. These results indicated that NO within the PVN, but not in systemic circulation, may play a role on the attenuation of the pressor responses elicited by SS. The dysfunction of NO release within the PVN may, in part, play a role in the exaggerated pressor responses in acute environmental stress.

  7. Regional haemodynamic effects of noradrenaline injected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats: possible mechanisms of action.

    Science.gov (United States)

    Bachelard, H; Harland, D; Gardiner, S M; Kemp, P A; Bennett, T

    1992-01-01

    The cardiovascular effects of noradrenaline bilaterally injected into the hypothalamic paraventricular nuclei were investigated in conscious, unrestrained Long-Evans rats and homozygous, vasopressin-deficient Brattleboro rats, chronically instrumented with pulsed Doppler probes for measurement of regional haemodynamics. In Long-Evans rats, incremental doses of noradrenaline (0.01-10 nmol) caused dose-related increases in blood pressure and a substantial, dose-related, superior mesenteric vasoconstriction. These changes were accompanied by bradycardia and reductions in renal and hind-quarter vascular conductances. In Brattleboro rats, noradrenaline (10 nmol) had no effect on blood pressure, heart rate, or renal or superior mesenteric vascular conductances. However, there was a slight vasodilatation in the vascular bed of the hindquarters. In Long-Evans rats, intravenous pretreatment with phentolamine had no effect on the bradycardia but partly inhibited the pressor response to noradrenaline injected into the paraventricular nuclei. These effects were associated with a smaller superior mesenteric vasoconstriction and an abolition of the vasoconstriction in the hindquarters. Combined intravenous pretreatment with phentolamine and propranolol had no effect on the heart rate or pressor responses to noradrenaline injected into the paraventricular nuclei, but reduced the superior mesenteric vasoconstriction, potentiated the vasoconstriction in the hindquarters and eliminated the renal vasoconstriction. These results suggest that, in untreated Long-Evans rats, alpha-adrenoceptor-mediated constriction in the mesenteric vascular bed and beta-adrenoceptor-mediated dilatation in the vascular bed of the hindquarters have important influences on the pressor response to noradrenaline injected into the paraventricular nuclei. In the presence of the vasopressin V1-receptor antagonist, d(CH2)5[Tyr(Et)]DAVP, the pressor and heart rate responses to noradrenaline injected into the

  8. The obesity-associated gene Negr1 regulates aspects of energy balance in rat hypothalamic areas.

    Science.gov (United States)

    Boender, Arjen J; van Gestel, Margriet A; Garner, Keith M; Luijendijk, Mieneke C M; Adan, Roger A H

    2014-07-01

    Neural growth regulator 1 (Negr1) is among the first common variants that have been associated with the regulation of body mass index. Using AAV technology directed to manipulate Negr1 expression in vivo, we find that decreased expression of Negr1 in periventricular hypothalamic areas leads to increases in body weight, presumably via increased food intake. Moreover, we observed that both increased and decreased levels of Negr1 lead to reduced locomotor activity and body temperature. In sum, our results provide further support for a role of hypothalamic expressed Negr1 in the regulation of energy balance. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  9. Total Flavonoids Extracted from Xiaobuxin-Tang on the Hyperactivity of Hypothalamic-Pituitary-Adrenal Axis in Chronically Stressed Rats

    Directory of Open Access Journals (Sweden)

    Lei An

    2011-01-01

    Full Text Available Our previous studies have demonstrated that the total flavonoids (XBXT-2 isolated from the extract of Xiaobuxin-Tang (XBXT, a traditional Chinese herbal decoction, ameliorated behavioral alterations and hippocampal dysfunctions in chronically stressed rats. Studies over the last decades have suggested that the hyperactivity of hypothalamic-pituitary-adrenal (HPA axis is one of the most consistent findings in stress-related depression. Herein, we used the same chronic mild stress model of rats as before to further investigate the effect of XBXT-2 on the hyperactivity of HPA axis, including the stress hormones levels and glucocorticoid receptors (GRs expression. Our ELISA results showed that chronic administration of XBXT-2 (25, 50 mg kg−1, p.o., 28 days, the effective doses for behavioral responses significantly decreased serum corticosterone level and its upstream stress hormone adrenocorticotropic hormone (ACTH level in chronically stressed rats. Furthermore, western blotting result demonstrated XBXT-2 treatment ameliorated stress-induced decrease of GRs expression in hippocampus, an important target involved in the hyperactivity of HPA axis. These results were similar to that of classic antidepressant imipramine treatment (10 mg kg−1, p.o.. In conclusion, the modulation of HPA axis produced by XBXT-2, including the inhibition of stress hormones levels and up-regulation of hippocampal GRs expression, may be an important mechanism underlying its antidepressant-like effect in chronically stressed rats.

  10. Cranial irradiation modulates hypothalamic-pituitary-adrenal axis activity and corticosteroid receptor expression in the hippocampus of juvenile rat.

    Science.gov (United States)

    Velickovic, Natasa; Djordjevic, Ana; Drakulic, Dunja; Stanojevic, Ivana; Secerov, Bojana; Horvat, Anica

    2009-01-01

    Glucocorticoids, essential for normal hypothalamic-pituitary-adrenal (HPA) axis activity, exert their action on the hippocampus through two types of corticosteroid receptors: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Recent studies report that exposure of juvenile rats to cranial irradiation adversely affects HPA axis stability leading to its activation along with radiation- induced inflammation. This study was aimed to examine the acute effects of radiation on HPA axis activity and hippocampal corticosteroid receptor expression in 18-day-old rats. Since immobilization was part of irradiation procedure, both irradiated and sham-irradiated animals were exposed to this unavoidable stress. Our results demonstrate that the irradiated rats exhibited different pattern of corticosteroid receptor expression and hormone levels compared to respective controls. These differences included upregulation of GR protein in the hippocampus with a concomitant elevation of GR mRNA and an increase in circulating level of corticosterone. In addition, the expression of MR, both at the level of protein and gene expression, was not altered. Taken together, this study demonstrates that cranial irradiation in juvenile rats leads to enhanced HPA axis activity and increased relative GR/MR ratio in hippocampus. The present paper intends to show that neuroendocrine response of normal brain tissue to localized irradiation comprise both activation of HPA axis and altered corticosteroid receptor balance, probably as consequence of innate immune activation.

  11. Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat.

    Science.gov (United States)

    Wang, Q; Bing, C; Al-Barazanji, K; Mossakowaska, D E; Wang, X M; McBay, D L; Neville, W A; Taddayon, M; Pickavance, L; Dryden, S; Thomas, M E; McHale, M T; Gloyer, I S; Wilson, S; Buckingham, R; Arch, J R; Trayhurn, P; Williams, G

    1997-03-01

    Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) are postulated to control energy balance by stimulating feeding and inhibiting thermogenesis, especially under conditions of energy deficit. We investigated whether leptin's short-term effects on energy balance are mediated by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected into the lateral ventricle of fasted adult Wistar rats inhibited food intake by 20-25% between 2 and 6 h after administration, compared with saline-treated controls (P ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P 0.1), but plasma leptin levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN neurons may interact in a homeostatic loop to regulate body fat mass and energy balance.

  12. Changes in hypothalamic [correction of hypothalmic] staining for c-Fos following 2G exposure in rats.

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    Fuller, C A; Murakami, D M; Hoban-Higgins, T M; Tang, I H

    1994-05-01

    The static gravitational field of the earth has been an important selective pressure that has shaped the evolution of biological organisms. This is illustrated by the evolution of tetrapods from a water environment where gravitational force was partially negated to a terrestrial environment where gravity is of greater consequence. Terrestrial invasion resulted in a series of new structural, physiological, and behavioral features. Therefore, it is not surprising that alterations in the gravitational field can cause widespread effects in many physiological systems and behaviors. Our previous studies have demonstrated that both exposure to hyperdynamic fields and the microgravity condition of space flight have significant effects on body temperature, heartrate, activity, feeding, drinking, and circadian rhythms. However, it has not been determined whether these physiological adaptations are associated with changes in neural activity within the hypothalamic nuclei that regulate these functions. This study examined the changes in body temperature, activity, body weight and food and water intake in rats caused by exposure to a hyperdynamic field. In addition, the immediate early gene activation marker, c-Fos, was used to examine potential protein synthesis changes in the hypothalamic nuclei that regulate these functions.

  13. Region- and sex-specific changes in CART mRNA in rat hypothalamic nuclei induced by forced swim stress.

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    Balkan, Burcu; Gozen, Oguz; Koylu, Ersin O; Keser, Aysegul; Kuhar, Michael J; Pogun, Sakire

    2012-10-15

    Cocaine and amphetamine regulated transcript (CART) mRNA and peptides are highly expressed in the paraventricular (PVN), dorsomedial (DMH) and arcuate (ARC) nuclei of the hypothalamus. It has been suggested that these nuclei regulate the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system activity, and feeding behavior. Our previous studies showed that forced swim stress augmented CART peptide expression significantly in whole hypothalamus of male rats. In another study, forced swim stress increased the number of CART-immunoreactive cells in female PVN, whereas no effect was observed in male PVN or in the ARC nucleus of either sex. In the present study, we evaluated the effect of forced swim stress on CART mRNA expression in PVN, DMH and ARC nuclei in both male and female rats. Twelve male (stressed and controls, n=6 each) and 12 female (stressed and controls, n=6 each) Sprague-Dawley rats were used. Control animals were only handled, whereas forced swim stress procedure was applied to the stressed groups. Brains were dissected and brain sections containing PVN, DMH and ARC nuclei were prepared. CART mRNA levels were determined by in situ hybridization. In male rats, forced swim stress upregulated CART mRNA expression in DMH and downregulated it in the ARC. In female rats, forced swim stress increased CART mRNA expression in PVN and DMH, whereas a decrease was observed in the ARC nucleus. Our results show that forced swim stress elicits region- and sex-specific changes in CART mRNA expression in rat hypothalamus that may help in explaining some of the effects of stress.

  14. Dietary whey reduces energy intake and alters hypothalamic gene expression in obese phyto-oestrogen-deprived male rats.

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    Andreoli, María F; Stoker, Cora; Lazzarino, Gisela P; Canesini, Guillermina; Luque, Enrique H; Ramos, Jorge G

    2016-09-01

    Removing dietary phyto-oestrogens in adult male rats causes obesity and diabetes. As whey proteins have been reported to reduce food intake and improve glucose homoeostasis, we investigated whether they could attenuate susceptibility to obesity and diabetes due to phyto-oestrogen deprivation. To this end, thirty male Wistar rats were fed a high-phyto-oestrogen (HP) or a phyto-oestrogen-free (PF) diet for 10 weeks; six rats from each group were killed. The remaining HP animals (six animals) continued receiving the HP diet for 6 weeks. The remaining PF rats (twelve rats) were divided in two groups: one was given the PF diet and the other a variation of the PF diet plus whey protein (PF-W). Body weight, food intake and adipose tissue weights were recorded. Hypothalamic mRNA expressions of orexigenic (neuropeptide Y, agouti-related protein (AgRP)) and anorexigenic (pro-opiomelanocortin (POMC), cocaine-amphetamine-related transcript (CART)) neuropeptides were quantified by real-time PCR. Serum glucose, insulin and total thyroxine (T4), thyroid-stimulating hormone, testosterone and oestradiol were assessed. After 10 weeks of PF diet, increased body weight, adiposity and energy intake, with up-regulation of AgRP and down-regulation of POMC', were observed. Longer treatment exacerbated these results, increased total T4 levels, reduced oestradiol levels and impaired glucose homoeostasis. PF-W reduced energy intake and increased POMC expression; however, body weight and adiposity remained unchanged. PF-W could not prevent the hormonal changes or the high circulating glucose levels induced by phyto-oestrogen deprivation, but reduced fasting insulin. These data demonstrate that, although 6 weeks of whey administration could not prevent obesity in phyto-oestrogen-deprived rats, the reduction in energy intake and circulating insulin could be beneficial with longer treatments.

  15. Hypothalamic dysfunction

    Science.gov (United States)

    ... common causes of hypothalamic dysfunction are surgery, traumatic brain injury, tumors, and radiation. Other causes include: Anorexia nervosa or bulimia Bleeding Genetic disorders that cause iron ...

  16. Effect of Nourishing “Yin”-Removing “Fire” Chinese Herbal Mixture on Hypothalamic NKB/NK3R Expression in Female Precocious Rats

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    Shiran Wang

    2014-01-01

    Full Text Available Aim. The present study aims to investigate the effects of nourishing “Yin”-removing “Fire” Chinese herb mixture on the hypothalamic NKB/NK3R expression in female precocious model rats. Materials and Methods. Female Sprague-Dawley rats were randomly divided into four groups: normal (N, central precocious puberty (CPP model (M, CPP fed with Chinese herbal mixture (CHM, and CPP fed with normal saline (MS. Rats on postnatal day 5 were given a single subcutaneous injection of 300 μg to establish CPP model rats. Rats of CHM and MS groups were continuously administered with nourishing “Yin”-removing “Fire” Chinese herb mixture or saline since postnatal day 15. The expressions of hypothalamic NKB/NK3R were detected by means of real-time PCR, western blot, and immunofluorescence histochemistry. Results. The day of vaginal opening and establishment of two regular estrous cycles were delayed in the CHM group compared with M and MS groups. The expression of hypothalamic NKB/NK3R mRNA and protein in the arcuate nucleus (ARC and medial preoptic (MPO area were decreased significantly in the CHM group compared with the M and MS groups on the day of onset-puberty. Conclusions. These results indicate that the NKB/NK3R signaling pathway might be involved in the effect of herbal mixture treatment on CPP.

  17. Metabolic Impact of Light Phase-Restricted Fructose Consumption Is Linked to Changes in Hypothalamic AMPK Phosphorylation and Melatonin Production in Rats

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    Juliana de Almeida Faria

    2017-03-01

    Full Text Available Recent studies show that the metabolic effects of fructose may vary depending on the phase of its consumption along with the light/dark cycle. Here, we investigated the metabolic outcomes of fructose consumption by rats during either the light (LPF or the dark (DPF phases of the light/dark cycle. This experimental approach was combined with other interventions, including restriction of chow availability to the dark phase, melatonin administration or intracerebroventricular inhibition of adenosine monophosphate-activated protein kinase (AMPK with Compound C. LPF, but not DPF rats, exhibited increased hypothalamic AMPK phosphorylation, glucose intolerance, reduced urinary 6-sulfatoxymelatonin (6-S-Mel (a metabolite of melatonin and increased corticosterone levels. LPF, but not DPF rats, also exhibited increased chow ingestion during the light phase. The mentioned changes were blunted by Compound C. LPF rats subjected to dark phase-restricted feeding still exhibited increased hypothalamic AMPK phosphorylation but failed to develop the endocrine and metabolic changes. Moreover, melatonin administration to LPF rats reduced corticosterone and prevented glucose intolerance. Altogether, the present data suggests that consumption of fructose during the light phase results in out-of-phase feeding due to increased hypothalamic AMPK phosphorylation. This shift in spontaneous chow ingestion is responsible for the reduction of 6-S-Mel and glucose intolerance.

  18. Effects of perinatal exposure to phthalate/adipate esters on hypothalamic gene expression and sexual behavior in rats.

    Science.gov (United States)

    Lee, Hwi-Cheul; Yamanouchi, Keitaro; Nishihara, Masugi

    2006-06-01

    Our previous research has identified the granulin (grn) and p130 genes as sex steroid-regulated genes in the neonatal rat hypothalamus that might be involved in sexual differentiation of the brain. Since phthalate/adipate esters such as di-n-butyl phthalate (DBP), diisononyl phthalate (DINP), and di-2-ethylhexyl adipate (DEHA) are suspected to interfere with the endocrine system as environmental endocrine disruptors having estrogenic or antiandrogenic properties, these chemicals may affect sexual differentiation of the brain. The present study assessed the effects of perinatal exposure to DBP, DINP, and DEHA on grn and p130 mRNA expressions in the hypothalamus on postnatal day (PND) 7 and sexual behaviors after maturation in rats. Maternal rats were given a phytoestrogen-free diet containing different doses of DBP (20, 200, 2,000, and 10,000 ppm), DINP (40, 400, 4,000, and 20,000 ppm) and DEHA (480, 2,400, and 12,000 ppm) from gestational day 15 to the day of weaning (PND 21). DBP and DINP exposure during the perinatal period resulted in an increase in hypothalamic grn and p130 mRNA levels in females and males, respectively, but DEHA exposure decreased expression levels of grn in males and p130 in females, although the effects were not dose-dependent. After maturation, male rats that were exposed to several doses of DBP, DINP, and DEHA displayed decreased copulatory behavior. The lordosis quotient was decreased in females perinatally exposed to DBP, DINP, and DEHA at all the doses used. On the other hand, serum levels of LH and FSH in both sexes and the estrous cycles in females were not affected by the treatments. These results suggest that inappropriate expression of grn and/or p130 genes in the brains of male and female neonatal rats by perinatal exposure to these chemicals may exert permanent effects on the hypothalamus, thereby decreasing sexual behavior after maturation.

  19. Hypothalamic-pituitary adrenal (HPAA) axis function in adult Fischer-344 rats exposed during development to neurotoxic chemicals perinatally.

    Science.gov (United States)

    Rosecrans, J A; Johnson, J H; Tilson, H A; Hong, J S

    1984-01-01

    The major objective of these experiments was to determine long-term effects on the hypothalamic-pituitary adrenal axis (HPAA) of adult rats exposed during development to chlordecone, an organochlorine insecticide. Chlordecone was administered to mothers prenatally plus the first 12 days of the neonatal period (6 ppm in the diet) or neonatally via a single subcutaneous injection to rats at 4 days of age (1 mg/pup in 20 micrograms of DMSO). DMSO (20 microliters/pup) and dexamethasone (100 micrograms/pup in 20 microliters saline) were also injected on day 4. HPAA function was evaluated at 70-80 days of age. Responsiveness of the HPAA to a repeated stressor was evaluated by exposing rats of each treatment group to a 7-day stress-induced analgesia (SIA) paradigm consisting of a daily 15 sec foot-shock (0.9 mA) exposure which was preceded by a 15 sec white noise conditioned stimulus. The behavioral response to daily stress was evaluated by measuring tail-flick latencies immediately before and/or after each stress exposure. The conditioned response to stress was evaluated 24 hours after the last of 7 daily foot-shock sessions in which rats of each treatment and experimental group were exposed to the shock chamber only. All rats were killed 15 minutes after the final session and tissue (serum and adrenals) were removed and frozen for later chemical analysis; serum and adrenal corticosterone (CS) and serum prolactin (Prl) levels were measured. Perinatal exposure to chlordecone did not significantly alter the behavioral and/or neuroendocrine responses to stress. Ambient hormone levels (both CS and Prl), however, were uniformly attenuated by chlordecone.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Mct8 and trh co-expression throughout the hypothalamic paraventricular nucleus is modified by dehydration-induced anorexia in rats.

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    Alvarez-Salas, Elena; Mengod, Guadalupe; García-Luna, Cinthia; Soberanes-Chávez, Paulina; Matamoros-Trejo, Gilberto; de Gortari, Patricia

    2016-04-01

    Thyrotropin-releasing hormone (TRH) is a neuropeptide with endocrine and neuromodulatory effects. TRH from the paraventricular hypothalamic nucleus (PVN) participates in the control of energy homeostasis; as a neuromodulator TRH has anorexigenic effects. Negative energy balance decreases PVN TRH expression and TSH concentration; in contrast, a particular model of anorexia (dehydration) induces in rats a paradoxical increase in TRH expression in hypophysiotropic cells from caudal PVN and high TSH serum levels, despite their apparent hypothalamic hyperthyroidism and low body weight. We compared here the mRNA co-expression pattern of one of the brain thyroid hormones' transporters, the monocarboxylate transporter-8 (MCT8) with that of TRH in PVN subdivisions of dehydration-induced anorexic (DIA) and control rats. Our aim was to identify whether a low MCT8 expression in anorexic rats could contribute to their high TRH mRNA content.We registered daily food intake and body weight of 7-day DIA and control rats and analyzed TRH and MCT8 mRNA co-expression throughout the PVN by double in situ hybridization assays. We found that DIA rats showed increased number of TRHergic cells in caudal PVN, as well as a decreased percentage of TRH-expressing neurons that co-expressed MCT8 mRNA signal. Results suggest that the reduced proportion of double TRH/MCT8 expressing cells may be limiting the entry of hypothalamic triiodothyronine to the greater number of TRH-expressing neurons from caudal PVN and be in part responsible for the high TRH expression in anorexia rats and for the lack of adaptation of their hypothalamic-pituitary-thyroid axis to their low food intake.

  1. The responses of hypothalamic NPY and OBRb mRNA expression to food deprivation develop during the neonatal-prepubertal period and exhibit gender differences in rats.

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    Matsuzaki, Toshiya; Iwasa, Takeshi; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Kawami, Takako; Yamasaki, Mikio; Murakami, Masahiro; Kato, Takeshi; Kuwahara, Akira; Yasui, Toshiyuki; Irahara, Minoru

    2015-04-01

    Neuropeptide Y (NPY) is an important hypothalamic orexigenic neuropeptide that acts in the brain. It has been established that the fasting-induced up-regulation of NPY expression is mainly caused by a reduction in the activity of leptin, which is a hormone secreted by adipose tissue. We have reported that in female rats hypothalamic NPY mRNA expression does not respond to fasting during the early neonatal period, but subsequently becomes sensitive to it later in the neonatal period. In this study, we compared the developmental changes in the responses of NPY and leptin expression to fasting between male and female rats during the neonatal to pre-pubertal period. Fasting was induced by maternal deprivation during the pre-weaning period (postnatal days 10 and 20) and by food deprivation during the post-weaning period (postnatal day 30). Hypothalamic NPY mRNA expression was not affected by fasting on postnatal day 10, whereas it was increased by fasting on postnatal day 20 and 30 in both males and females. On the other hand, the serum leptin level was decreased by fasting at all examined ages in both sexes. Namely, hypothalamic NPY mRNA expression was not correlated with the reduction in the serum leptin level at postnatal day 10 in either sex. Under the fasted conditions, the hypothalamic NPY mRNA levels of the males were higher than those of the females on postnatal days 20 and 30, whereas no such differences were observed under the normal nourishment conditions. The serum leptin levels observed under the fasted conditions did not differ between males and females at any examined age. These results suggest that some hypothalamic NPY functions develop during the neonatal period and that there is no major difference between the sexes with regard to the time when NPY neurons become sensitive to fasting. They also indicate that hypothalamic NPY expression is more sensitive to under-nutrition in male rats than in female rats, at least during the pre-pubertal period.

  2. l-Leucine Supplementation Worsens the Adiposity of Already Obese Rats by Promoting a Hypothalamic Pattern of Gene Expression that Favors Fat Accumulation

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    Thais T. Zampieri

    2014-04-01

    Full Text Available Several studies showed that l-leucine supplementation reduces adiposity when provided before the onset of obesity. We studied rats that were exposed to a high-fat diet (HFD for 10 weeks before they started to receive l-leucine supplementation. Fat mass was increased in l-leucine-supplemented rats consuming the HFD. Accordingly, l-leucine produced a hypothalamic pattern of gene expression that favors fat accumulation. In conclusion, l-leucine supplementation worsened the adiposity of rats previously exposed to HFD possibly by central mechanisms.

  3. Synaptic innervation to rat hippocampus by vasopressin-immuno-positive fibres from the hypothalamic supraoptic and paraventricular nuclei.

    Science.gov (United States)

    Zhang, L; Hernández, V S

    2013-01-03

    The neuropeptide arginine vasopressin (AVP) exerts a modulatory role on hippocampal excitability through vasopressin V(1A) and V(1B) receptors. However, the origin and mode of termination of the AVP innervation of the hippocampus remain unknown. We have used light and electron microscopy to trace the origin, distribution and synaptic relationships of AVP-immuno-positive fibres and nerve terminals in the rat hippocampus. Immuno-positive fibres were present in all areas (CA1-3, dentate gyrus) of the whole septo-temporal extent of the hippocampus; they had the highest density in the CA2 region, strongly increasing in density towards the ventral hippocampus. Two types of fibres were identified, both establishing synaptic junctions. Type A had large varicosities packed with immuno-positive large-granulated peptidergic vesicles and few small clear vesicles forming type I synaptic junctions with pyramidal neuron dendrites, dendritic spines and with axonal spines. Type B had smaller varicosities containing mostly small clear vesicles and only a few large-granulated vesicles and established type II synaptic junctions mainly with interneuron dendrites. The AVP-positive axons in stratum oriens appeared to follow and contact metabotropic glutamate receptor 1α (mGluR1α)-immuno-positive interneuron dendrites. Fluoro-Gold injection into the hippocampus revealed retrogradely labelled AVP-positive somata in hypothalamic supraoptic and paraventricular nuclei. Hypothalamo-hippocampal AVP-positive axons entered the hippocampus mostly through a ventral route, also innervating the amygdala and to a lesser extent through the dorsal fimbria fornix, in continuation of the septal AVP innervation. Thus, it appears the AVP-containing neurons of the magnocellular hypothalamic nuclei serve as important sources for hippocampal AVP innervation, although the AVP-expressing neurons located in amygdala and bed nucleus of the stria terminalis reported previously may also contribute.

  4. Sleep deprivation alters energy homeostasis through non-compensatory alterations in hypothalamic insulin receptors in Wistar rats.

    Science.gov (United States)

    Moraes, Danilo Alves; Venancio, Daniel Paulino; Suchecki, Deborah

    2014-11-01

    Studies have shown a gradual reduction of sleep time in the general population, accompanied by increased food intake, representing a risk for developing obesity, type II diabetes and cardiovascular disease. Rats subjected to paradoxical sleep deprivation (PSD) exhibit feeding and metabolic alterations, both of which are regulated by the communication between peripheral signals and the hypothalamus. This study aimed to investigate the daily change of 96 h of PSD-induced food intake, body weight, blood glucose, plasma insulin and leptin concentrations and the expression of their receptors in the hypothalamus of Wistar rats. Food intake was assessed during the light and dark phases and was progressively increased in sleep-deprived animals, during the light phase. PSD produced body weight loss, particularly on the first day, and decreased plasma insulin and leptin levels, without change in blood glucose levels. Reduced leptin levels were compensated by increased expression of leptin receptors in the hypothalamus, whereas no compensations occurred in insulin receptors. The present results on body weight loss and increased food intake replicate previous studies from our group. The fact that reduced insulin levels did not lead to compensatory changes in hypothalamic insulin receptors, suggests that this hormone may be, at least in part, responsible for PSD-induced dysregulation in energy metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats.

    Science.gov (United States)

    Faria, Juliana A; Kinote, Andrezza; Ignacio-Souza, Letícia M; de Araújo, Thiago M; Razolli, Daniela S; Doneda, Diego L; Paschoal, Lívia B; Lellis-Santos, Camilo; Bertolini, Gisele L; Velloso, Lício A; Bordin, Silvana; Anhê, Gabriel F

    2013-07-15

    Melatonin can contribute to glucose homeostasis either by decreasing gluconeogenesis or by counteracting insulin resistance in distinct models of obesity. However, the precise mechanism through which melatonin controls glucose homeostasis is not completely understood. Male Wistar rats were administered an intracerebroventricular (icv) injection of melatonin and one of following: an icv injection of a phosphatidylinositol 3-kinase (PI3K) inhibitor, an icv injection of a melatonin receptor (MT) antagonist, or an intraperitoneal (ip) injection of a muscarinic receptor antagonist. Anesthetized rats were subjected to pyruvate tolerance test to estimate in vivo glucose clearance after pyruvate load and in situ liver perfusion to assess hepatic gluconeogenesis. The hypothalamus was removed to determine Akt phosphorylation. Melatonin injections in the central nervous system suppressed hepatic gluconeogenesis and increased hypothalamic Akt phosphorylation. These effects of melatonin were suppressed either by icv injections of PI3K inhibitors and MT antagonists and by ip injection of a muscarinic receptor antagonist. We conclude that melatonin activates hypothalamus-liver communication that may contribute to circadian adjustments of gluconeogenesis. These data further suggest a physiopathological relationship between the circadian disruptions in metabolism and reduced levels of melatonin found in type 2 diabetes patients.

  6. Specific Features of the Hypothalamic Leptin Signaling Response to Cold Exposure Are Reflected in Peripheral Blood Mononuclear Cells in Rats and Ferrets

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    Bàrbara Reynés

    2017-08-01

    Full Text Available Objectives: Cold exposure induces hyperphagia to counteract fat loss related to lipid mobilization and thermogenic activation. The aim of this study was investigate on the molecular mechanisms involved in cold-induced compensatory hyperphagia.Methods: We analyzed the effect of cold exposure on gene expression of orexigenic and anorexigenic peptides, and of leptin signaling-related genes in the hypothalamus of rats at different ages (1, 2, 4, and 6 months, as well as in ferrets. We also evaluated the potential of peripheral blood mononuclear cells to reflect hypothalamic molecular responses.Results: As expected, cold exposure induced hypoleptinemia in rats, which could be responsible for the increased ratio of orexigenic/anorexigenic peptides gene expression in the hypothalamus, mainly due to decreased anorexigenic gene expression, especially in young animals. In ferrets, which resemble humans more closely, cold exposure induced greater changes in hypothalamic mRNA levels of orexigenic genes. Despite the key role of leptin in food intake control, the effect of cold exposure on the expression of key hypothalamic leptin signaling cascade genes is not clear. In our study, cold exposure seemed to affect leptin signaling in 4-month-old rats (increased Socs3 and Lepr expression, likely associated with the smaller-increase in food intake and decreased body weight observed at this particular age. Similarly, cold exposed ferrets showed greater hypothalamic Socs3 and Stat3 gene expression. Interestingly, peripheral blood mononuclear cells (PBMC mimicked the hypothalamic increase in Lepr and Socs3 observed in 4-month-old rats, and the increased Socs3 mRNA expression observed in ferrets in response to cold exposure.Conclusions: The most outstanding result of our study is that PBMC reflected the specific modulation of leptin signaling observed in both animal models, rats and ferrets, which points forwards PBMC as easily obtainable biological material to be

  7. Medial Forebrain Bundle Deep Brain Stimulation has Symptom-specific Anti-depressant Effects in Rats and as Opposed to Ventromedial Prefrontal Cortex Stimulation Interacts With the Reward System.

    Science.gov (United States)

    Edemann-Callesen, Henriette; Voget, Mareike; Empl, Laura; Vogel, Martin; Wieske, Franziska; Rummel, Julia; Heinz, Andreas; Mathé, Aleksander A; Hadar, Ravit; Winter, Christine

    2015-01-01

    In recent years, deep brain stimulation (DBS) has emerged as a promising treatment option for patients suffering from treatment-resistant depression (TRD). Several stimulation targets have successfully been tested in clinical settings, including the subgenual cingulum (Cg25) and the medial forebrain bundle (MFB). MFB-DBS has led to remarkable results, surpassing the effect of previous targets in terms of response latency and number of responders. However, the question remains as to which mechanisms underlie this difference. The aim of the present study was to thoroughly study the anti-depressant effect of MFB-DBS in the Flinders sensitive line (FSL) rat model of depression as well as to investigate whether MFB-DBS and Cg25-DBS operate through the same neurobiological circuits. FSL and control rats received bilateral high-frequency stimulation to the MFB at the level of the lateral hypothalamus, while being subjected to a variety of depression- and anxiety-related behavioral paradigms. To further compare the effects of MFB-DBS and Cg25-DBS on reward-related behavior, animals were stimulated in either the MFB or ventromedial prefrontal cortex (vmPFC, rodent analog to Cg25), while being tested in the intra-cranial self-stimulation paradigm. A marked symptom-specific anti-depressant effect of MFB-DBS was demonstrated. The ICSS-paradigm revealed that MFB-DBS, as opposed to vmPFC-DBS interacts with the reward system. Our data suggest that MFB-DBS and Cg25-DBS do not operate via the same neurobiological circuits. This differentiation might be of interest when selecting patients for either Cg25- or MFB-DBS. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Norepinephrine uptake by hypothalamic tissue from the rat related to feeding

    NARCIS (Netherlands)

    Gugten, J. van der; Slangen, J.L.

    1957-01-01

    Norepinephrine (NE) uptake by rat hypothalamus in vitro was studied in relation to food intake. Significant daily variations in NE uptake were observed in caudal hypothalamus from freely feeding rats. A maximal elevation occurred at the beginning of the night when food intake is also increasing to a

  9. Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with adriamycin-induced heart failure.

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    Min Zheng

    Full Text Available BACKGROUND: The paraventricular nucleus (PVN of the hypothalamus plays an important role in the progression of heart failure (HF. We investigated whether cyclooxygenase-2 (COX-2 inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS and renin-angiotensin system (RAS in rats with adriamycin-induced heart failure. METHODOLOGY/PRINCIPAL FINDING: Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg. On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW and lung to body weight (LW/BW ratios, heart rate (HR, left ventricular end-diastolic pressure (LVEDP, left ventricular peak systolic pressure (LVPSP and maximum rate of change in left ventricular pressure (LV±dp/dtmax were improved in HF+CLB rats. Angiotensin II (ANG II, norepinephrine (NE, COX-2 and glutamate (Glu in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats. CONCLUSIONS: These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure.

  10. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

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    Vanessa R. Yingling

    2016-01-01

    Full Text Available Background. Osteoporosis is “a pediatric disease with geriatric consequences.” Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV at maturity.Methods. Female rats (25 days old were assigned to a control (C group (n = 45 that received saline injections (.2 cc or an experimental group (GnRH-a (n = 45 that received gonadotropin releasing hormone antagonist injections (.24 mg per dose for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a. The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R (n = 15 and (G-R (n = 15. The remaining animals had an ovariectomy surgery (OVX at 185 days of age and were sacrificed 40 days later (C-OVX (n = 15 and (G-OVX (n = 15. After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX and insulin-like growth factor 1 (IGF-1 were measured. Two-way ANOVA (2 groups (GnRH-a and Control X 3 time points (Injection Protocol, Recovery, post-OVX was computed.Results. GnRH-a injections suppressed uterine weights (72% and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19% following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  11. Evidence for a role of nitric oxide in hindlimb vasodilation induced by hypothalamic stimulation in anesthetized rats

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    Marcos L. Ferreira-Neto

    2005-06-01

    Full Text Available Electrical stimulation of the hypothalamus produces cardiovascular adjustments consisting of hypertension, tachycardia, visceral vasoconstriction and hindlimb vasodilation. Previous studies have demonstrated that hindlimb vasodilation is due a reduction of sympathetic vasoconstrictor tone and to activation of beta2-adrenergic receptors by catecholamine release. However, the existence of a yet unidentified vasodilator mechanism has also been proposed. Recent studies have suggested that nitric oxide (NO may be involved. The aim of the present study was to investigate the role of NO in the hindquarter vasodilation in response to hypothalamic stimulation. In pentobarbital-anesthetized rats hypothalamic stimulation (100 Hz, 150µA, 6 s produced hypertension, tachycardia, hindquarter vasodilation and mesenteric vasoconstriction. Alpha-adrenoceptor blockade with phentolamine (1.5 mg/kg, iv plus bilateral adrenalectomy did not modify hypertension, tachycardia or mesenteric vasoconstriction induced by hypothalamic stimulation. Hindquarter vasodilation was strongly reduced but not abolished. The remaining vasodilation was completely abolished after iv injection of the NOS inhibitor L-NAME (20 mg/kg, iv. To properly evaluate the role of the mechanism of NO in hindquarter vasodilation, in a second group of animals L-NAME was administered before alpha-adrenoceptor blockade plus adrenalectomy. L-NAME treatment strongly reduced hindquarter vasodilation in magnitude and duration. These results suggest that NO is involved in the hindquarter vasodilation produced by hypothalamic stimulation.Em animais anestesiados a EE do hipotálamo produz um padrão de ajustes cardiovasculares caracterizado por hipertensão arterial, taquicardia, vasodilatação muscular e vasoconstrição mesentérica, entretanto, os mecanismos periféricos envolvidos nestes ajustes cardiovasculares ainda não foram completamente esclarecidos. O presente estudo teve como objetivo caracterizar

  12. Hypothalamic Npy mRNA is correlated with increased wheel running and decreased body fat in calorie-restricted rats.

    Science.gov (United States)

    Ruegsegger, Gregory N; Speichinger, Katherine R; Manier, Jacob B; Younger, Kyle M; Childs, Thomas E; Booth, Frank W

    2016-04-01

    The neuro-molecular mechanisms that regulate the relationship between physical activity level, energy homeostasis regulation, and body fat are unclear. Thus, we aimed to investigate the relationship between mRNAs in the hypothalamic arcuate nucleus (ARC) related to energy homeostasis, wheel running distance, and body fat in ad lib (AL) and calorie-restricted (CR) growing rats. We hypothesized that changes in select mRNAs (Pomc, Cart, Agrp, Npy, Lepr, Insr, Mc4r, Ampk, Sirt1, Sirt3) in CR would be associated with decreases in body fat percentage and increased wheel running behavior. Male Wistar rats were given access to voluntary running wheels at 4 weeks of age and randomized into AL (n=8) and CR (70% of AL; n=7) groups at 5 weeks of age until study termination at 12 weeks of age. Body composition, serum leptin, insulin, and adiponectin, and ARC mRNA expression in AL and CR rats were assessed and correlated with week-12 running distance to examine potential relationships that may exist. By 12 weeks of age, wheel running was increased ∼3.3-fold (p=0.03) while body fat percentage was ∼2-fold lower in CR compared to AL (p=0.001). Compared to AL, ARC Npy mRNA expression was ∼2-fold greater in CR (p=0.02), while Lepr, Insr, Ampk, and Sirt1 mRNA were additionally increased in CR (pNpy mRNA levels versus week-12 wheel running distance (r=0.81, p=0.03), body fat (r=-0.93, pNpy action.

  13. Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge

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    Erin Jane Campbell

    2015-03-01

    Full Text Available Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS, during the neonatal period has been shown to alter both neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress and nociceptive processing. However, whether neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in later life remains to be determined. Male Wistar rats (n=13 were exposed to either LPS or saline (0.05mg/kg, i.p on postnatal days (PND 3 and 5. On PND 80-97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin. Following behavioural testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. Rats treated with LPS during the neonatal period exhibited decreased licking behaviours during the interphase of the formalin test, the period typically associated with the active inhibition of pain, and increased grooming responses to formalin in adulthood. Interestingly, these behavioural changes were accompanied by an increase in the percentage of Fos-positive orexin cells in the dorsomedial and perifornical hypothalamus in LPS-exposed animals. Similar increases in Fos-protein were also observed in stress and pain sensitive brain regions that receive orexinergic inputs. These findings highlight a potential role for orexin in the behavioural responses to pain and provide further evidence that early life stress can prime the circuitry responsible for these responses in adulthood.

  14. The decrease in hypothalamic dopamine secretion induced by suckling: comparison of voltammetric and radioisotopic methods of measurement. [Rats

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    Plotsky, P.M.; Neill, J.D.

    1982-03-01

    Previous in situ voltammetric microelectrode measurements of median eminence dopamine release during mammary nerve stimulation of anesthetized lactating rats revealed a transient (1-3 min) 70% decline of dopamine concentrations. This dopamine was believed to be destined for secretion into the hypophysial portal circulation, but direct experimental support for this supposition was lacking. Thus, in the present study, (3H)dopamine release into brief sequential samples of hypophysial portal blood was compared with dopamine release in the median eminence measured by voltammetry. Lactating female rats were urethane anesthetized, and the median eminence pituitary region was exposed. (3H)Tyrosine was injected into a jugular cannula (100 microCi) followed by continuous infusion (5 microCi/min). In a preliminary experiment, this regimen produced a steady state level of (3H)dopamine in the portal blood within 45 min. In subsequent experiments, portal blood was collected as sequential 3-min samples, and electrochemical sampling from a microelectrode placed in the median eminence occurred at 1-min intervals. Electrochemical current resulting from the oxidation of dopamine in the medial median eminence was unvarying throughout the 75-min experiment in control rats (n . 4) and during the 30-min control period preceding mammary nerve stimulation in the other group (n . 4). These results were paralled by (3H) dopamine levels in portal blood during the same periods of time. All animals showed simultaneous decreases in oxidation current and (3H)dopamine levels within 1-4 min after initiation of mammary nerve stimulation. These and earlier results demonstrate that mammary nerve stimulation (and by extension, suckling) induces a momentary, but profound, decrease in hypothalamic dopamine secretion which precedes or accompanies the rise in PRL secretion evoked by the same stimulus.

  15. Activation of hypothalamic neuronal nitric oxide synthase in lithium-induced diabetes insipidus rats.

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    Anai, H; Ueta, Y; Serino, R; Nomura, M; Nakashima, Y; Yamashita, H

    2001-02-01

    The expression of the neuronal nitric oxide synthase (nNOS) gene in the paraventricular (PVN) and supraoptic nuclei (SON) in rats with lithium (Li)-induced polyuria was examined by using in situ hybridization histochemistry. The state of the thyroid axis in these rats was also examined by in situ hybridization histochemistry for thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) mRNAs and radioimmunoassay for circulating thyroid hormones. Adult male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed remarkable polyuria. The urine in the Li-treated rats was hypotonic and had a large volume and low ionic concentration. The nNOS mRNA in the PVN and SON was significantly increased in the Li-treated rats in comparison with that in control. The increased levels of the nNOS mRNA in the PVN and SON were confirmed by NADPH-diaphorase histochemical staining. There were no differences of TRH mRNA in the PVN, TSH mRNA in the anterior pituitary and plasma concentrations of free T3 and free T4 between Li-treated rats and control rats. These results suggest that Li-induced diabetes insipidus may activate nNOS in the PVN and SON without change of the thyroid axis.

  16. Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction?

    National Research Council Canada - National Science Library

    Cifani, Carlo; Micioni Di Bonaventura, Maria V; Pucci, Mariangela; Giusepponi, Maria E; Romano, Adele; Di Francesco, Andrea; Maccarrone, Mauro; D'Addario, Claudio

    2015-01-01

    .... To investigate the individual sensitivity to weight gain/resistance, we here studied gene transcription regulation of several hypothalamic neuropeptides involved in the control of energy balance...

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

    Science.gov (United States)

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

    2015-12-01

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

  18. Re-purposing of histological tissue sections for corroborative western blot analysis of hypothalamic metabolic neuropeptide expression following delineation of transactivated structures by Fos immuno-mapping.

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    Alenazi, Fahaad S H; Ibrahim, Baher A; Briski, Karen P

    2015-04-01

    Fos immunocytochemistry is a valuable anatomical mapping tool for distinguishing cells within complex tissues that undergo genomic activation, but it is seldom paired with corroborative molecular analytical techniques. Due to preparatory requirements that include protein cross-linking for specimen sectioning, histological tissue sections are regarded as unsuitable for those methods. Our studies show that pharmacological activation of the hindbrain energy sensor AMPK by AICAR elicits estradiol (E)-dependent patterns of Fos immunolabeling of hypothalamic metabolic loci. Here, Western blotting was applied to hypothalamic tissue removed from histological sections of E- versus oil (O)-implanted ovariectomized (OVX) female rat brain to measure levels of metabolic transmitters associated with Fos-positive structures. In both E and O rats, AICAR treatment elicited alterations in pro-opiomelanocortin, neuropeptide Y, SF-1, and orexin-A neuropeptide expression that coincided with patterns of Fos labeling of structures containing neurons that synthesize these neurotransmitters, e.g. arcuate and ventromedial nuclei and lateral hypothalamic area. O, but not E animals also exhibited parallel augmentation of tissue corticotropin-releasing hormone neuropeptide levels and paraventricular nucleus Fos staining. Data demonstrate the utility of immunoblot analysis as a follow-through technique to capitalize on Fos mapping of transactivation sites in the brain. Findings that induction of Fos immunoreactivity coincides with adjustments in hypothalamic metabolic neuropeptide expression affirms that this functional indicator reflects changes in neurotransmission in pathways governing metabolic outflow. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Functional magnetic resonance imaging and immunohistochemical study of hypothalamic function following oral glucose ingestion in rats

    Institute of Scientific and Technical Information of China (English)

    CHEN Min; ZHAO Wei-feng; LI Sa-ying; WANG Zhi; ZHANG Yun-ting; LI Guo-zhen; ZHANG Tie-mei; LUO Sen-lin; ZHOU Cheng; WU Xiao-meng; ZHOU Ni-na; CAI Kui; YANG Zhen-han; WANG Wen-chao

    2007-01-01

    Background The hypothalamus plays a central role in the regulation of metabolism by sensing metabolic demands and releasing regulatory neurotransmitters. This study investigated the response of the hypothalamus to glucose ingestion in rats by blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and immunohistochemical techniques to determine the role of the hypothalamus in glycoregulation during disturbances in carbohydrate metabolism.Methods The signal intensity of the hypothalamus was monitored by fMRI for 60 minutes after oral glucose intake in 48 healthy rats (age 14 months), which included 24 normal weight rats (weighing (365±76.5) g) and 24 overweight rats (weighing (714±83.5) g). Then, 12 rats (6 normal, 6 overweight) underwent a repeat fMRI scan after consuming an equivalent amount of water without glucose on a separate day. The procedure for fMRI with water intake was the same as for glucose ingestion. fMRI data was processed using time cluster analysis and intensity averaging method. After fMRI,the expression of neuropeptide Y (NPY) and 5-hydroxytryptamine (5-HT) in the hypothalamus of all rats was determined by immunohistochemistry. Positive cells for NPY or 5-HT were counted.Results There was a transient, but significant, decrease in fMRI signal intensity in all rats (mean (3.12±0.78)%) in the hypothalamus within 19.5-25.5 minutes of oral glucose ingestion. In overweight rats, the decrease in signal intensity in response to the glucose ingestion was more markedly attenuated than that observed in normal weight rats ((2.2±1.5)%vs (4.2±0.7)% inhibition, t=2.12, P<0.05). There was no significant response in the hypothalamus after oral water ingestion. The percentage of NPY positive cells in obese rats were slightly lower than those in control group (21% vs 23%,t=0.71, P>0.05); but there was no significant difference between the two groups; the percentage of 5-HT positive cells in obese rats were significantly lower than

  20. Activity correlations between on-like and off-like cells of the rostral ventromedial medulla and simultaneously recorded wide-dynamic-range neurons of the spinal dorsal horn in rats.

    Science.gov (United States)

    Salas, Rafael; Ramirez, Karla; Vanegas, Horacio; Vazquez, Enrique

    2016-12-01

    Considerable evidence supports the notion that on- and off-cells of the rostral ventromedial medulla (RVM) facilitate and depress, respectively, spinal nociceptive transmission. This notion stems from a covariation of on- or off-cell activities and spinal nocifensive reflexes. Such covariation could theoretically be due to their independently responding to a common source, or to an RVM-derived modulation of ventral horn neurons. Here, we tested whether on- and off-cells indeed modulate spinal nociceptive neurons. In deeply anesthetized rats, unitary recordings were simultaneously made from an RVM on-like or off-like cell and a spinal nociceptive neuron that shared a receptive field (RF) at a hind paw. Action potential firing in RVM/spinal neuron pairs was highly correlated, positively for on-like cells and negatively for off-like cells, both during ongoing activity and during application of calibrated noxious pressure to the RF. Microinjection of morphine into RVM induced a correlated decrease in on-like cell/spinal neuron ongoing activity and response to noxious stimulation. RVM morphine induced changes in off-like cell activity that were not correlated with spinal neuronal activity. These results suggest that on-cells exert a positive modulation upon spinal nociceptive neurons, upstream to ventral horn circuits and plausibly at the origin of nociceptive information that eventually reaches the cerebral cortex. On-cells may in this manner contribute to inflammation- and neuropathy-induced increases in withdrawal reflexes. Most significantly, on-cell modulation of nociceptive neurons may be a key factor in clinical pain conditions such as hyperalgesia and allodynia.

  1. Expression of hippocampal corticosteroid receptors, as well as corticotrophin-releasing hormone and vasopressin in the hypothalamic paraventricular nucleus, in fornix transected rats

    Institute of Scientific and Technical Information of China (English)

    Fang Han; Hong Liu; Yanhui Zhang; Yuxiu Shi

    2009-01-01

    BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventdcular nucleus receives neuronal input from the hippocampus via the fornix.OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fomix.DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008.MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster.METHODS: A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups (n=45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection.MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection.RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventricular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopressin expression in the paraventricular nucleus were observed (P < 0.05-0.01).CONCLUSION: Negative feedback from the

  2. Effect of animal facility construction on basal hypothalamic-pituitary-adrenal and renin-aldosterone activity in the rat.

    Science.gov (United States)

    Raff, Hershel; Bruder, Eric D; Cullinan, William E; Ziegler, Dana R; Cohen, Eric P

    2011-04-01

    Although loud noise and intense vibration are known to alter the behavior and phenotype of laboratory animals, little is known about the effects of nearby construction. We studied the effect of a nearby construction project on the classic stress hormones ACTH, corticosterone, renin, and aldosterone in rats residing in a barrier animal facility before, for the first 3 months of a construction project, and at 1 month after all construction was completed. During some of the construction, noise and vibrations were not obvious to investigators inside the animal rooms. Body weight matched for age was not altered by nearby construction. During nearby construction, plasma ACTH, corticosterone, and aldosterone were approximately doubled compared with those of pre- and postconstruction levels. Expression of CRH mRNA in the paraventricular nucleus of the hypothalamus, CRH receptor and POMC mRNA in the anterior pituitary, and most mRNAs for steroidogenic genes in the adrenal gland were not significantly changed during construction. We conclude that nearby construction can cause a stress response without long-term effects on hypothalamic-pituitary-adrenal axis gene expression and body weight.

  3. Preliminary Study of Quercetin Affecting the Hypothalamic-Pituitary-Gonadal Axis on Rat Endometriosis Model

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    Yang Cao

    2014-01-01

    Full Text Available In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endometrium on rat endometriosis model may be through the decreasing of serum FSH and LH levels and then reducing local estrogen content to make the ectopic endometrium atrophy. Quercetin can decrease the expression of ERα, ERβ, and PR in hypothalamus, pituitary, and endometrium, thereby inhibiting estrogen and progesterone binding to their receptors to play the role of antiestrogen and progesterone.

  4. Sex differences in hypothalamic-mediated tonic norepinephrine release for thermal hyperalgesia in rats.

    Science.gov (United States)

    Wagner, M; Banerjee, T; Jeong, Y; Holden, J E

    2016-06-02

    Neuropathic pain is treated using serotonin norepinephrine reuptake inhibitors with mixed results. Pain facilitation mediated by α1-adrenoceptors may be involved, but whether norepinephrine (NE) is tonically released is unclear. The aim of this study was to determine whether NE is tonically released from A7 cells following chronic constriction injury (CCI), and if the lateral hypothalamus (LH) plays a role in this release in male and female rats with nociceptive and neuropathic pain types. Neuropathic groups received left CCI while nociceptive groups remained naïve to injury. Fourteen days later, rats were given intrathecal infusion of either the α1-adrenoceptor antagonist WB4101, the α2-adrenoceptor antagonist yohimbine (74 μg), or normal saline for control. Paw withdrawal latency (PWL) from a thermal stimulus was measured. The generalized estimated equation method was used for statistical analysis. Nociceptive rats given WB4101 had a PWL significantly longer than saline control (7.89 ± 0.63 vs. 5.87 ± 0.52 s), while the PWL of neuropathic rats given WB4101 was 13.20 ± 0.52 s compared to 6.78 ± 0.52 s for the saline control rats. Yohimbine had no significant effect. Microinjection of cobalt chloride (CoCl) in the A7 catecholamine cell group to prevent synaptic transmission blocked the effect of WB4101 in all groups, supporting the notion that spinally descending A7 cells tonically release NE that contributes to α1-mediated nociceptive facilitation. Microinjection of CoCl into the left LH blocked the effect of WB4101 in nociceptive and neuropathic male rats, but had no effect in female rats of either pain type, suggesting differential innervation. These findings indicate that tonic release of NE acts at pronociceptive α1-adrenoceptors, that this effect is greater in rats with nerve damage, and that, while NE comes primarily from the A7 cell group, LH innervation of the A7 cell group is different between the sexes.

  5. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    Directory of Open Access Journals (Sweden)

    Hojatollah Karimi Jashni

    2016-02-01

    Full Text Available Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, 200, 400 mg/kg/bw of aqueous extract of asparagus roots. All dosages were administered orally for 28 days. Blood samples were taken from rats to evaluate serum levels of Gonadotropin releasing hormone (GnRH, follicular stimulating hormone (FSH, Luteinal hormone (LH, estrogen, and progesterone hormones. The ovaries were removed, weighted, sectioned, and studied by light microscope. Results: Dose-dependent aqueous extract of asparagus roots significantly increased serum levels of GnRH, FSH, LH, estrogen, and progestin hormones compared to control and sham groups. Increase in number of ovarian follicles and corpus luteum in groups treated with asparagus root extract was also observed (p<0.05. Conclusion: Asparagus roots extract stimulates secretion of hypothalamic- pituitary- gonadal axis hormones. This also positively affects oogenesis in female rats.

  6. The Fos expression in rat brain following electrical stimulation of dura mater surrounding the superior sagittal sinus changed with the pre-treatment of rizatriptan benzoate.

    Science.gov (United States)

    Wang, Xiaolin; Yu, Shengyuan; Dong, Zhao; Jiang, Lei

    2011-01-07

    Fos expression in the brain was systematically investigated by means of immunohistochemical staining after electrical stimulation of the dura mater surrounding the superior sagittal sinus in conscious rats. Fos-like immunoreactive neurons are distributed mainly in the upper cervical spinal cord, spinal trigeminal nucleus caudal part, raphe magnus nucleus, periaqueductal gray, ventromedial hypothalamic nucleus, and mediodorsal thalamus nucleus. With the pre-treatment of intraperitoneal injection of rizatriptan benzoate, the number of Fos-like immunoreactive neurons decreased in the spinal trigeminal nucleus caudal part and raphe magnus nucleus, increased in the periaqueductal gray, and remained unchanged in the ventromedial hypothalamic nucleus and mediodorsal thalamus nucleus. These results provide morphological evidence that the nuclei described above are involved in the development and maintenance of the trigeminovascular headache.

  7. Properties of native P2X receptors in large multipolar neurons dissociated from rat hypothalamic arcuate nucleus.

    Science.gov (United States)

    Wakamori, Minoru; Sorimachi, Masaru

    2004-04-16

    ATP, the ligand of P2X receptors, is a candidate of neurotransmitter or co-transmitter in the peripheral and the central nervous systems. Anatomical studies have revealed the wide distribution of P2X receptors in the brain. So far, P2X-mediated small synaptic responses have been recorded in some brain regions. To determine the physiological significance of postsynaptic ATP receptors in the brain, we have investigated the P2X responses in rat dissociated hypothalamic arcuate neurons by using the patch-clamp technique. ATP evoked inward currents in a concentration-dependent manner (EC(50)=42 microM) at a holding potential of -70 mV. The current-voltage relationship showed a marked inward rectification starting around -10 mV. Although neither 300 microM alphabeta-methylene-ATP nor 300 microM betagamma-methylene-ATP induced any currents, 100 microM ATPgammaS and 100 microM 2-methylthio-ATP evoked inward currents of which amplitude was about 60% of the control currents evoked by 100 microM ATP. PPADS, one of P2 receptor antagonists, inhibited the ATP-evoked currents in a time- and a concentration-dependent manners (IC(50)=19 microM at 2 min). Permeant Ca(2+) inhibited the ATP-evoked currents in the range of millimolars (IC(50)=7 mM); however, Cd(2+) (1-300 microM), a broad cation channel blocker, facilitated the currents with slow off-response. Zn(2+) in the range of 1-100 microM facilitated the currents whereas Zn(2+) at the concentrations over 100 microM inhibited the currents. These observations suggest that functional P2X receptors are expressed in the hypothalamic arcuate nucleus. The most likely subunit combinations of the P2X receptors are P2X(2)-homomultimer and P2X(2)/P2X(6)-heteromultimer.

  8. Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats

    Science.gov (United States)

    Hoffman, Gloria E.; Koban, Michael

    2016-01-01

    A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC), would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD) because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness. PMID:27997552

  9. Enhanced defensiveness and increased food motivation each contribute to aggression and success in food competition by rats with medial hypothalamic lesions.

    Science.gov (United States)

    Albert, D J; Petrovic, D M; Jonik, R H; Walsh, M L

    1991-01-01

    Castrated male rats (N = 27) with medial hypothalamic lesions or sham lesions were placed on a 23-h food-deprivation schedule and adapted to a highly palatable liquid food. They were also given two tests of defensiveness toward an experimenter. All animals were then housed in medial hypothalamic lesion/sham lesion pairs and subjected to a series of 6 competition tests (1 per day). Following the competition tests, all animals were given individual food consumption tests and a third test of defensiveness toward an experimenter. Correlational analysis showed that postcompetition defensiveness scores but not precompetition defensiveness scores or individual food consumption were related to aggression during the food competition. Analysis by criterion groups indicated that animals high in precompetition defensiveness and with food consumption in the normal range were not more successful in the competition but were slightly more aggressive than their sham-lesioned competitors. Animals with high postcompetition defensiveness scores and with individual food consumption in the normal range were more successful than their sham-lesioned competitors and the most aggressive of the lesioned animals during the food competition. Animals that were high in food consumption and only moderately defensive were also more successful but only slightly more aggressive in the food competition than their sham-lesioned competitors. These results suggest that a high and stable level of defensiveness, and excessive food intake, each contribute to the success and aggressiveness of rats with medial hypothalamic lesions in a food competition situation.

  10. Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

    Science.gov (United States)

    Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

    2015-01-01

    Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

  11. Spontaneous and electrochemically stimulated changes in plasma LH in the female rat following hypothalamic deafferentation.

    Science.gov (United States)

    Phelps, C P; Krieg, R J; Sawyer, C H

    1976-01-16

    Plasma LH levels in adult female rats were studied by radioimmunoassay 6 weeks after making frontal cuts (FC) at the optic chiasm with Halász knives of various sizes. Cuts made with a small knife (radius 1.3 mm) permitted a spontaneous rise in plasma LH during proestrus from a mean of 96 +/- 25 ng/ml at 14:00 h to 545 +/- 207 ng/ml at 18:00 h in 13 rats. Seven of the latter, with a mean plasma LH of 967 +/- 281 ng/ml at 18:00 h exhibited tubal ova at hemicastration (hemi-ovx) the following morning. In a similar experiment 6 FC females lesioned with a 1.5 mm knife had plasma LH levels of 53 +/- 7 ng/ml at 14:00 h, but showed neither detectable changes at 2 h intervals through 20:00 h nor ovulation at hemi-ovx. Similar results were obtained in 13 rats deafferented with a 2.0 mm knife. Nine weeks after FC and 3 weeks following hemi-ovx all animals were given pentobarbital (32 mg/kg i.p.) at 13:30 h and stimulated bilaterally in the medial preoptic area (MPO) passing 20 muA anodal DC X 60 sec through concentric bipolar steel electrodes placed 0.8 mm from the midline. All 3 groups of FC animals showed increases in plasma LH to comparable levels (range: 197 +/- 45-357 +/- 156 ng/ml) 1 h after stimulation. Electrochemical stimulation sites extended lateral to the cut locations on at least one side in all animals. The results of these studies suggest that chronically (9 week) deafferented female rats have the capacity to release pituitary LH in response to MPO electrochemical stimulation in spite of retrochiasmatic deafferentation, but that the ovaries of the persistent estrus rat are unresponsive to these amounts of circulating LH.

  12. Hyperosmotic stimulus induces reversible angiogenesis within the hypothalamic magnocellular nuclei of the adult rat: a potential role for neuronal vascular endothelial growth factor

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    Vincent Anne

    2005-03-01

    Full Text Available Abstract Background In mammals, the CNS vasculature is established during the postnatal period via active angiogenesis, providing different brain regions with capillary networks of various densities that locally supply adapted metabolic support to neurons. Thereafter this vasculature remains essentially quiescent excepted for specific pathologies. In the adult rat hypothalamus, a particularly dense network of capillary vessels is associated with the supraoptic (SON and paraventricular (PVN nuclei containing the magnocellular neurons secreting vasopressin and oxytocin, two neurohormones involved in the control of the body fluid homoeostasis. In the seventies, it was reported that proliferation of astrocytes and endothelial cells occurs within these hypothalamic nuclei when strong metabolic activation of the vasopressinergic and oxytocinergic neurons was induced by prolonged hyperosmotic stimulation. The aim of the present study was to determine whether such proliferative response to osmotic stimulus is related to local angiogenesis and to elucidate the cellular and molecular mechanisms involved. Results Our results provide evidence that cell proliferation occurring within the SON of osmotically stimulated adult rats corresponds to local angiogenesis. We show that 1 a large majority of the SON proliferative cells is associated with capillary vessels, 2 this proliferative response correlates with a progressive increase in density of the capillary network within the nucleus, and 3 SON capillary vessels exhibit an increased expression of nestin and vimentin, two markers of newly formed vessels. Contrasting with most adult CNS neurons, hypothalamic magnocellular neurons were found to express vascular endothelial growth factor (VEGF, a potent angiogenic factor whose production was increased by osmotic stimulus. When VEGF was inhibited by dexamethasone treatment or by the local application of a blocking antibody, the angiogenic response was strongly

  13. Inhibition of Cyclooxygenase-2 Reduces Hypothalamic Excitation in Rats with Adriamycin-Induced Heart Failure

    OpenAIRE

    2012-01-01

    BACKGROUND: The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the progression of heart failure (HF). We investigated whether cyclooxygenase-2 (COX-2) inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in rats with adriamycin-induced heart failure. METHODOLOGY/PRINCIPAL FINDING: Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg...

  14. Developmental changes in the hypothalamic mRNA expression levels of brain-derived neurotrophic factor and serum leptin levels: Their responses to fasting in male and female rats.

    Science.gov (United States)

    Iwasa, Takeshi; Matsuzaki, Toshiya; Yano, Kiyohito; Munkhzaya, Munkhsaikhan; Tungalagsuvd, Altankhuu; Yiliyasi, Maira; Kuwahara, Akira; Irahara, Minoru

    2016-11-01

    The actions and responses of hypothalamic appetite regulatory factors change markedly during the neonatal to pre-pubertal period in order to maintain appropriate metabolic and nutritional conditions. In this study, we examined the developmental changes in the hypothalamic mRNA levels of brain-derived neurotrophic factor (BDNF), which is a potent anorectic factor and the changes in the sensitivity of the hypothalamic expression of this factor to fasting during the neonatal to pre-pubertal period. Under fed conditions, hypothalamic BDNF mRNA expression decreased during development in both male and female rats. Similarly, the serum levels of leptin, which is a positive regulator of hypothalamic BDNF expression, also tended to fall during the developmental period. The serum leptin level and the hypothalamic BDNF mRNA level were found to be positively correlated in both sexes under the fed conditions. Hypothalamic BDNF mRNA expression was decreased by 24h fasting (separating the rats from their mothers) in the early neonatal period (postnatal day 10) in both males and females, but no such changes were seen at postnatal day 20. Twenty-four hours' fasting (food deprivation) did not affect hypothalamic BDNF mRNA expression in the pre-pubertal period (postnatal day 30). On the other hand, the rats' serum leptin levels were decreased by 24h fasting (separating the rats from their mothers at postnatal day 10 and 20, and food deprivation at postnatal day 30) throughout the early neonatal to pre-pubertal period. The correlation between serum leptin and hypothalamic BDNF mRNA levels was not significant under the fasted conditions. It can be speculated that leptin partially regulates hypothalamic BDNF mRNA levels, but only in fed conditions. Such changes in hypothalamic BDNF expression might play a role in maintaining appropriate metabolic and nutritional conditions and promoting normal physical development. In addition, because maternal separation induces a negative energy

  15. Expression and localization of IL-18 in the hypothalamic-pituitary-ovarian axis of non-pregnant, pregnant, and abortive rats.

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    Wang, Yuesi; Zhang, Xiuli; Zhang, Yan; Xu, Hui; Fang, Guangli

    2011-12-01

    Cytokines present in the reproductive system play an important role both in the modulation of immune responses to infectious challenge and in the establishment and maintenance of pregnancy. Interleukin 18 (IL-18) has been regarded as an important regulator of innate and acquired immune response, but its expression and distribution in the hypothalamic-pituitary-ovarian axis remain unclear. In this paper, the expression and distribution of IL-18 in non-pregnant, pregnant, and early abortive rats were examined using an ultra-sensitive immunohistochemical streptavidin-peroxidase method, enzyme-linked immunosorbent assay, and reverse transcription-polymerase chain reaction. The results showed that IL-18 expression in the pituitary, in follicular ovaries, and in the corpus luteum of abortive rats were significantly lower than that of pregnant and non-pregnant rats. However, the staining of IL-18 in the hypothalamus, interstitial glands of the ovary, and uterus of abortive rats was strikingly stronger than those of the non-pregnant ones. IL-18 mRNA expression in rat uterus was detected in all groups, whereas IL-18 mRNA content in abortive rat uterus was significantly higher than in normal pregnant rats. Further, IL-18 in the peripheral blood serum of abortive rats was significantly lower than in same-period normal pregnant rats. The differential expression of IL-18 in early abortion suggests that IL-18 may be related to the underlying mechanisms of abortion.

  16. Hypothalamic neuron projection to autonomic preganglionic levels related with glucose metabolism: a fluorescent labelling study in the rat.

    Science.gov (United States)

    Portillo, F; Carrasco, M; Vallo, J J

    1996-06-01

    The location of hypothalamic paraventricular neurons projecting to sympathetic preganglionic levels and related to the autonomic regulation of various organs involved in glucose metabolism (OGM) was determined by ipsilateral injections of two fluorescent tracers, Diamidino Yellow into the left dorsal motor nucleus of the vagus and Fast Blue into the left intermediolateral cell column of the T8-T9 spinal cord. Hypothalamospinal neurons were mainly located in the dorsal part of the paraventricular hypothalamic nucleus (PVH) and the hypothalamobulbar neurons were most abundant in the ventral, medial and extreme lateral parts of the PVH. No double-labelled neurons were found in the hypothalamus. These results can help the knowledge of the neural hypothalamic network related with the autonomic hypothalamic control.

  17. Caffeine-induced activated glucocorticoid metabolism in the hippocampus causes hypothalamic-pituitary-adrenal axis inhibition in fetal rats.

    Science.gov (United States)

    Xu, Dan; Zhang, Benjian; Liang, Gai; Ping, Jie; Kou, Hao; Li, Xiaojun; Xiong, Jie; Hu, Dongcai; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-01-01

    Epidemiological investigations have shown that fetuses with intrauterine growth retardation (IUGR) are susceptible to adult metabolic syndrome. Clinical investigations and experiments have demonstrated that caffeine is a definite inducer of IUGR, as children who ingest caffeine-containing food or drinks are highly susceptible to adult obesity and hypertension. Our goals for this study were to investigate the effect of prenatal caffeine ingestion on the functional development of the fetal hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis and to clarify an intrauterine HPA axis-associated neuroendocrine alteration induced by caffeine. Pregnant Wistar rats were intragastrically administered 20, 60, and 180 mg/kg · d caffeine from gestational days 11-20. The results show that prenatal caffeine ingestion significantly decreased the expression of fetal hypothalamus corticotrophin-releasing hormone. The fetal adrenal cortex changed into slight and the expression of fetal adrenal steroid acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc), as well as the level of fetal adrenal endogenous corticosterone (CORT), were all significantly decreased after caffeine treatment. Moreover, caffeine ingestion significantly increased the levels of maternal and fetal blood CORT and decreased the expression of placental 11β-hydroxysteroid dehydrogenase-2 (11β-HSD-2). Additionally, both in vivo and in vitro studies show that caffeine can downregulate the expression of fetal hippocampal 11β-HSD-2, promote the expression of 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor (GR), and enhance DNA methylation within the hippocampal 11β-HSD-2 promoter. These results suggest that prenatal caffeine ingestion inhibits the development of the fetal HPA axis, which may be associated with the fetal overexposure to maternal glucocorticoid and activated glucocorticoid metabolism in the fetal hippocampus. These results will be beneficial in

  18. Down-regulation of hypothalamic pro-opiomelanocortin (POMC) expression after weaning is associated with hyperphagia-induced obesity in JCR rats overexpressing neuropeptide Y.

    Science.gov (United States)

    Diané, Abdoulaye; Pierce, W David; Russell, James C; Heth, C Donald; Vine, Donna F; Richard, Denis; Proctor, Spencer D

    2014-03-14

    We hypothesised that hypothalamic feeding-related neuropeptides are differentially expressed in obese-prone and lean-prone rats and trigger overeating-induced obesity. To test this hypothesis, in the present study, we measured energy balance and hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA expressions in male JCR:LA-cp rats. We compared, in independent cohorts, free-feeding obese-prone (Obese-FF) and lean-prone (Lean-FF) rats at pre-weaning (10 d old), weaning (21-25 d old) and early adulthood (8-12 weeks). A group of Obese-pair-feeding (PF) rats pair-fed to the Lean-FF rats was included in the adult cohort. The body weights of 10-d-old Obese-FF and Lean-FF pups were not significantly different. However, when the pups were shifted from dams' milk to solid food (weaning), the obese-prone rats exhibited more energy intake over the days than the lean-prone rats and higher body and fat pad weights and fasting plasma glucose, leptin, insulin and lipid levels. These differences were consistent with higher energy consumption and lower energy expenditure. In the young adult cohort, the differences between the Obese-FF and Lean-FF rats became more pronounced, yielding significant age effects on most of the parameters of the metabolic syndrome, which were reduced in the Obese-PF rats. The obese-prone rats displayed higher NPY expression than the lean-prone rats at pre-weaning and weaning, and the expression levels did not differ by age. In contrast, POMC expression exhibited significant age-by-genotype differences. At pre-weaning, there was no genotype difference in POMC expression, but in the weanling cohort, obese-prone pups exhibited lower POMC expression than the lean-prone rats. This genotype difference became more pronounced at adulthood. Overall, the development of hyperphagia-induced obesity in obese-prone JCR rats is related to POMC expression down-regulation in the presence of established NPY overexpression.

  19. GABAergic and Cortical and Subcortical Glutamatergic Axon Terminals Contain CB1 Cannabinoid Receptors in the Ventromedial Nucleus of the Hypothalamus

    OpenAIRE

    Leire Reguero; Nagore Puente; Izaskun Elezgarai; Juan Mendizabal-Zubiaga; Miren Josune Canduela; Ianire Buceta; Almudena Ramos; Juan Suárez; Fernando Rodríguez de Fonseca; Giovanni Marsicano; Pedro Grandes

    2011-01-01

    BACKGROUND: Type-1 cannabinoid receptors (CB(1)R) are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH) that participates in homeostatic and behavioral functions including food intake. Although CB(1)R activation modulates excitatory and inhibitory synaptic transmission in the brain, CB(1)R contribution to the molecular architecture of the excitatory and inhibitory synaptic terminals in the VMH is not known. Therefore, the aim of this study was to invest...

  20. Hypothalamic inflammation is reversed by endurance training in anorectic-cachectic rats

    Directory of Open Access Journals (Sweden)

    Lira Fábio S

    2011-08-01

    Full Text Available Abstract Aim We tested the effects of a cancer cachexia-anorexia sydrome upon the balance of anti and pro-inflammatory cytokines in the hypothalamus of sedentary or trained tumour-bearing (Walker-256 carcinosarcoma rats. Methods Animals were randomly assigned to a sedentary control (SC, sedentary tumour-bearing (ST, and sedentary pair-fed (SPF groups or, exercised control (EC, exercised tumour-bearing (ET and exercised pair-fed (EPF groups. Trained rats ran on a treadmill (60%VO2max for 60 min/d, 5 days/wk, for 8 wks. We evaluated food intake, leptin and cytokine (TNF-α, IL1β levels in the hypothalamus. Results The cumulative food intake and serum leptin concentration were reduced in ST compared to SC. Leptin gene expression in the retroperitoneal adipose tissue (RPAT was increased in SPF in comparison with SC and ST, and in the mesenteric adipose tissue (MEAT the same parameter was decreased in ST in relation to SC. Leptin levels in RPAT and MEAT were decreased in ST, when compared with SC. Exercise training was also able to reduce tumour weight when compared to ST group. In the hypothalamus, IL-1β and IL-10 gene expression was higher in ST than in SC and SPF. Cytokine concentration in hypothalamus was higher in ST (TNF-α and IL-1β, p Conclusion Cancer-induced anorexia leads towards a pro-inflammatory state in the hypothalamus, which is prevented by endurance training which induces an anti-inflammatory state, with concomitant decrease of tumour weight.

  1. Participation of ghrelin signalling in the reciprocal regulation of hypothalamic NPY/POMC-mediated appetite control in amphetamine-treated rats.

    Science.gov (United States)

    Yu, Ching-Han; Chu, Shu-Chen; Chen, Pei-Ni; Hsieh, Yih-Shou; Kuo, Dong-Yih

    2017-02-14

    Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) have been documented to participate in amphetamine (AMPH)-induced appetite suppression. This study investigated whether ghrelin signalling is associated with changes in NPY/POMC-mediated appetite control. Rats were given AMPH daily for four days, and changes in food intake, body weight, plasma ghrelin, hypothalamic NPY, melanocortin 3 receptor (MC3R), ghrelin O-acyltransferase (GOAT), acyl ghrelin (AG) and ghrelin receptor (GHSR1a) were examined and compared. Food intake, body weight and NPY expression decreased, while MC3R expression increased and expressed reciprocally to NPY expression during AMPH treatment. Plasma ghrelin and hypothalamic AG/GOAT/GHSR1a expression decreased on Day 1 and Day 2, which was associated with the positive energy metabolism, and returned to normal levels on Day 3 and Day 4, which was associated with the negative energy metabolism; this expression pattern was similar to that of NPY. Infusion with a GHSR1a antagonist or an NPY antisense into the brain enhanced the decrease in NPY and AG/GOAT/GHSR1a expression and the increase in MC3R expression compared to the AMPH-treated group. Peripheral ghrelin and the central ghrelin system participated in the regulation in AMPH-induced appetite control. These results shed light on the involvement of ghrelin signalling in reciprocal regulation of NPY/POMC-mediated appetite control and may prove useful for the development of anti-obesity drugs.

  2. Methyl vitamins contribute to obesogenic effects of a high multivitamin gestational diet and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring.

    Science.gov (United States)

    Cho, Clara E; Pannia, Emanuela; Huot, Pedro S P; Sánchez-Hernández, Diana; Kubant, Ruslan; Dodington, David W; Ward, Wendy E; Bazinet, Richard P; Anderson, G Harvey

    2015-03-01

    High multivitamin (HV, tenfold AIN-93G) gestational diets fed to Wistar rats increase food intake, obesity, and characteristics of metabolic syndrome in the offspring. We hypothesized that methyl vitamins, and specifically folate, in the HV gestational diet contribute to the obesogenic phenotypes consistent with their epigenetic effects on hypothalamic food intake regulatory mechanisms. Male offspring of dams fed the AIN-93G diet with high methyl vitamins (HMethyl; tenfold folate, vitamins B12, and B6) (Study 1) and HV with recommended folate (HVRF) (Study 2) were compared with those from HV and recommended vitamin (RV) fed dams. All offspring were weaned to a high fat diet for 8 wks. HMethyl diet, similar to HV, and compared to RV, resulted in higher food intake, body weight, and metabolic disturbances. Removing folate additions to the HV diet in HVRF offspring normalized the obesogenic phenotype. Methyl vitamins, and folate in HV diets, altered hypothalamic gene expression toward increased food intake concurrent with DNA methylation and leptin and insulin receptor signaling dysfunction. Methyl vitamins in HV gestational diets contribute to obesogenic phenotypes and epigenetic alterations in the hypothalamic feeding pathways in the offspring. Folate alone accounts for many of these effects. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Transient gastric irritation in the neonatal rats leads to changes in hypothalamic CRF expression, depression- and anxiety-like behavior as adults.

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    Liansheng Liu

    Full Text Available AIMS: A disturbance of the brain-gut axis is a prominent feature in functional bowel disorders (such as irritable bowel syndrome and functional dyspepsia and psychological abnormalities are often implicated in their pathogenesis. We hypothesized that psychological morbidity in these conditions may result from gastrointestinal problems, rather than causing them. METHODS: Functional dyspepsia was induced by neonatal gastric irritation in male rats. 10-day old male Sprague-Dawley rats received 0.1% iodoacetamide (IA or vehicle by oral gavage for 6 days. At 8-10 weeks of age, rats were tested with sucrose preference and forced-swimming tests to examine depression-like behavior. Elevated plus maze, open field and light-dark box tests were used to test anxiety-like behaviors. ACTH and corticosterone responses to a minor stressor, saline injection, and hypothalamic CRF expression were also measured. RESULTS: Behavioral tests revealed changes of anxiety- and depression-like behaviors in IA-treated, but not control rats. As compared with controls, hypothalamic and amygdaloid CRF immunoreactivity, basal levels of plasma corticosterone and stress-induced ACTH were significantly higher in IA-treated rats. Gastric sensory ablation with resiniferatoxin had no effect on behaviors but treatment with CRF type 1 receptor antagonist, antalarmin, reversed the depression-like behavior in IA-treated rats CONCLUSIONS: The present results suggest that transient gastric irritation in the neonatal period can induce a long lasting increase in depression- and anxiety-like behaviors, increased expression of CRF in the hypothalamus, and an increased sensitivity of HPA axis to stress. The depression-like behavior may be mediated by the CRF1 receptor. These findings have significant implications for the pathogenesis of psychological co-morbidity in patients with functional bowel disorders.

  4. Short-term enrichment makes male rats more attractive, more defensive and alters hypothalamic neurons.

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    Rupshi Mitra

    Full Text Available Innate behaviors are shaped by contingencies built during evolutionary history. On the other hand, environmental stimuli play a significant role in shaping behavior. In particular, a short period of environmental enrichment can enhance cognitive behavior, modify effects of stress on learned behaviors and induce brain plasticity. It is unclear if modulation by environment can extend to innate behaviors which are preserved by intense selection pressure. In the present report we investigate this issue by studying effects of relatively short (14-days environmental enrichment on two prominent innate behaviors in rats, avoidance of predator odors and ability of males to attract mates. We show that enrichment has strong effects on both the innate behaviors: a enriched males were more avoidant of a predator odor than non-enriched controls, and had a greater rise in corticosterone levels in response to the odor; and b had higher testosterone levels and were more attractive to females. Additionally, we demonstrate decrease in dendritic length of neurons of ventrolateral nucleus of hypothalamus, important for reproductive mate-choice and increase in the same in dorsomedial nucleus, important for defensive behavior. Thus, behavioral and hormonal observations provide evidence that a short period of environmental manipulation can alter innate behaviors, providing a good example of gene-environment interaction.

  5. Projection patterns of lateral hypothalamic, cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe and/or the locus coeruleus in the rat.

    Science.gov (United States)

    Yoon, Ye S; Lee, Hyun S

    2013-02-04

    The present study was designed to reveal the projection patterns of lateral hypothalamic (LH), cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe (DR) and/or the locus coeruleus (LC) in the rat. After the injection of Red or Green Retrobeads into the DR or LC, LH sections were immunostained for CART and/or melanin-concentrating hormone (MCH). First, CART-immunoreactive axon terminals formed close appositions to the DR (or LC) neuronal profiles. Second, a subpopulation of CART neurons containing MCH projected to the monoaminergic nuclei; the majority of labeled neurons were observed in the dorsal hypothalamic area, the dorsal part of the posterior hypothalamic area, and the zona incerta. Cells were also observed in the perifornical part of the LH, the dorsomedial hypothalamic nucleus, the peduncular and the magnocellular parts of the LH. Of the total population of DR (or LC)-projecting cells, CART/MCH co-containing neurons were 9.5% ± 1.6% (or 10.8% ± 1.3% for LC). Finally, a subset of CART (or MCH) neurons provided divergent axon collaterals to the DR and the LC. Of the entire CART (or MCH) cell population, 3.9% ± 0.8% (or 5.6% ± 1.0% for MCH) sent axon collaterals to the DR/LC. CART/MCH co-containing neurons projecting to the DR or LC might be involved in the feeding-related regulation of arousal, stress-related responses, and emotional behaviors. Thus, CART (or MCH) cells that send divergent axon collaterals to the DR/LC might have a simultaneous (and possibly more efficient) way to exert their specific influences on the aminergic nuclei.

  6. Relevance of dorsomedial hypothalamus, dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal gray matter in the organization of freezing or oriented and non-oriented escape emotional behaviors.

    Science.gov (United States)

    Ullah, Farhad; dos Anjos-Garcia, Tayllon; dos Santos, Ieda Regina; Biagioni, Audrey Francisco; Coimbra, Norberto Cysne

    2015-10-15

    Electrical stimulation of the periaqueductal gray matter and ventromedial hypothalamus in humans showed the involvement of both these structures in panic attacks. The aim of this work was to make clear the role of dorsal periaqueductal gray (dPAG) matter, dorsomedial hypothalamus (DMH) and the dorsomedial part of the ventromedial hypothalamus (dmVMH) in panic attack-like behaviors. DMH, dmVMH and dPAG of Wistar rats were treated with N-methyl- d-aspartic acid (NMDA) at different doses. The rodents were then kept in a polygonal arena with a burrow to record panic attack-like responses and oriented defensive behaviors. In dmVMH, 6nmol of NMDA elicited alertness, freezing and oriented escape. The same set of behaviors was elicited by DMH neurons when stimulated by 9nmol of NMDA. Treatment of dmVMH with 9nmol of NMDA elicited typical explosive behaviors followed by freezing and oriented behaviors. The stimulation of the dPAG with NMDA at different doses provoked alertness and freezing (1nmol) or alertness, freezing, tail twitching, explosive behavior and oriented escape (3nmol), and explosive behavior followed by long-lasting freezing (6nmol). These data suggest that mainly dPAG plays a role in panic attack-like behaviors that resemble panic syndrome in humans. However, hypothalamic nuclei like dmVMH that mainly elicits oriented escape, can also produce explosive reaction when stimulated with 9nmol NMDA, whereas, DMH plays a role in coordinating defensive behaviors.

  7. Hypothalamic obesity in children: pathophysiology to clinical management.

    Science.gov (United States)

    Haliloglu, Belma; Bereket, Abdullah

    2015-05-01

    Hypothalamic obesity (HyOb) is a complex neuroendocrine disorder caused by damage to the hypothalamus, which results in disruption of energy regulation. The key hypothalamic areas of energy regulation are the ARC (arcuate nucleus), the VMH (ventromedial hypothalamus), the PVN (paraventriculer nuclei) and the LHA (lateral hypothalamic area). These pathways can be disrupted mechanically by hypothalamic tumors, neurosurgery, inflammatory disorders, radiotherapy and trauma or functionally as such seen in genetic diseases. Rapid weight gain and severe obesity are the most striking features of HyOb and caused by hyperphagia, reduced basal metabolic rate (BMR) and decreased physical activity. HyOb is usually unresponsive to diet and exercise. Although, GLP-1 and its anologs seem to be a new agent, there is still no curative treatment. Thus, prevention is of prime importance and the clinicians should be alert and vigilant in patients at risk for development of HyOb.

  8. Differential expression of hypothalamic, metabolic and inflammatory genes in response to short-term calorie restriction in juvenile obese- and lean-prone JCR rats.

    Science.gov (United States)

    Diane, A; Pierce, W D; Mangat, R; Borthwick, F; Nelson, R; Russell, J C; Heth, C D; Jacobs, R L; Vine, D F; Proctor, S D

    2015-08-24

    Childhood obesity is an important early predictor of adult obesity and associated comorbidities. Common forms of obesity are underpinned by both environmental and genetic factors. However, the rising prevalence of obesity in genetically stable populations strongly suggests that contemporary lifestyle is a premier factor to the disease. In pediatric population, the current treatment/prevention options for obesity are lifestyle interventions such as caloric restriction (CR) and increase physical activity. In obese individuals, CR improves many metabolic parameters in peripheral tissues. Little is known about the effect of CR on the hypothalamus. This study aimed to assess the effect of CR on hypothalamic metabolic gene expression of young obese- and lean-prone animals. Male juvenile JCR:LA-cp obese-prone rats were freely fed (Obese-FF) or pair fed (Obese-FR) to lean-prone, free-feeding animals (Lean-FF). A group of lean-prone rats (Lean-FR) were matched for relative average degree of CR to Obese-FR rats. In free-feeding conditions, obese-prone rats consumed more energy than lean-prone rats (PJCR rats that the metabolic and inflammatory response of the brain to CR is genotype dependent.

  9. Prunus mume and Lithospermum erythrorhizon Extracts Synergistically Prevent Visceral Adiposity by Improving Energy Metabolism through Potentiating Hypothalamic Leptin and Insulin Signalling in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Byoung-Seob Ko

    2013-01-01

    Full Text Available We investigated the antiobesity and hypoglycemic properties of Prunus mume Sieb. et Zucc (PMA; Japanese apricot and Lithospermum erythrorhizon Sieb. et Zucc (LES; gromwell extracts in ovariectomized (OVX rats that impaired energy and glucose homeostasis. OVX rats consumed either 5% dextrose, 5% PMA extract, 5% LES extract, or 2.5% PMA+2.5% LES extract in the high fat diet. After 8 weeks of treatment, PMA+LES prevented weight gain and visceral fat accumulation in OVX rats by lowering daily food intake and increasing energy expenditure and fat oxidation. PMA+LES prevented the attenuation of leptin and insulin signaling by increasing the expression of leptin receptor in the hypothalamus in OVX rats. PMA+LES significantly reversed the decrease of energy expenditure in OVX rats by increasing expression of UCP-1 in the brown adipose tissues and UCP-2 and UCP-3 in the quadriceps muscles. PMA+LES also increased CPT-1 expression and decreased FAS, ACC, and SREBP-1c in the liver and quadriceps muscles to result in reducing triglyceride accumulation. PMA+LES improved insulin sensitivity in OVX rats. In conclusion, PMA+LES synergistically prevented the impairment of energy, lipid, and glucose metabolism by OVX through potentiating hypothalamic leptin and insulin signaling. PMA+LES may be a useful intervention for alleviating the symptoms of menopause in women.

  10. 延髓头端腹内侧区对大鼠心脏伤害性感受的下行调控作用%Descending modulation of cardiac nociception by the rostral ventromedial medulla in rats

    Institute of Scientific and Technical Information of China (English)

    孙娜; 孔令恒; 牛利刚; 朱娟霞; 徐燕; 杜剑青

    2013-01-01

    目的:观察延髓头端腹内侧区(rostroventral medulla, RVM)对大鼠心脏伤害性感受的下行调控作用。方法通过心包插管术制作心脏-躯体运动反射(cardiosomatic motor reflex, CMR)大鼠模型,采用RVM电刺激(强度分别为25、75和100μA)及RVM电损毁的方法,以心包内可复性注入致痛剂辣椒素(capsaicin, CAP)所诱发的背斜方肌肌电(EMG)为指标评估RVM对心脏伤害性感受的下行调控作用。结果 RVM内8个刺激位点对CAP注射诱发的EMG反应产生了强度依赖性的抑制作用(F[2,21]=43.188,P=0.001);3个刺激位点产生了完全易化效应,其易化的程度与刺激强度无关(F[2,6]=0.884,P=0.461);11个刺激位点对CAP注射诱发的EMG反应产生了双向调节作用,即低强度(25μA)刺激,EMG反应明显大于基础对照(P<0.05),高强度(75/100μA)刺激,EMG反应明显低于基础对照(P<0.05);RVM实施电损毁后,EMG反应明显高于损毁前及假损毁组(P<0.05)。结论心脏受到伤害性刺激后,RVM对大鼠心脏伤害性感受具有双向调控作用,且以下行抑制性调控作用为主。%Objective To observe the descending modulation of cardiac nociception by the rostral ventromedial medulla (RVM) in rats. Methods A rat model of cardiosomatic motor reflex (CMR) was established by injecting capsaicin into the pericardial sac to induce cardiac nociception, and the electromyogram (EMG) response of the dorsal spinotrapezius muscle was studied. The RVM was electricaly stimulated (25, 75 and 100 μA) or destroyed to examine whether RVM exerted descending modulation on cardiac nociception. Results Electrical stimulation of the RVM at 8 sites produced intensity-dependent inhibition of EMG responses to noxious cardiac stimulus (F[2,21]=43.188, P=0.001). Electrical stimulation at 3 sites caused facilitated EMG responses, but the increased magnitude of the EMG was not dependent on

  11. The medial hypothalamic defensive circuit and 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) induced fear: comparison of electrolytic and neurotoxic lesions.

    Science.gov (United States)

    Pagani, Jerome H; Rosen, Jeffrey B

    2009-08-25

    The neural circuits for unconditioned fear to predator odors (e.g., cat fur odor, trimethylthiazoline, TMT) are not well delineated. A putative neural circuit for predator odor fear, the medial hypothalamic defensive circuit (MHDC), consisting of the anterior hypothalamic (AHN), ventromedial hypothalamic (VMH) and dorsal premammillary nuclei (PMd), has been proposed. Electrolytic and ibotenic acid lesions of the PMd have been shown to reduce unconditioned fear in rats presented with either a cat or cat odor. Whether the PMd, AHN and VMH are involved in unconditioned fear to another predator odor derived from fox feces, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), has not been explored. The present study compared the effects of electrolytic and neurotoxic lesions of MHDC nuclei in rats on unconditioned fear to TMT and shock-induced contextually conditioned fear, as measured by freezing. Electrolytic lesions of the PMd did not reduce TMT-induced freezing, but diminished post-shock and shock-induced contextually conditioned freezing, suggesting a role for the PMd in contextually conditioned fear. In contrast, electrolytic lesions of the AHN and VMH reduced freezing to TMT while not affecting conditioned fear. However, neither NMDA lesions of the AHN nor ibotenic acid lesions of the VMH reduced freezing in shock-induced conditioned or TMT-induced unconditioned fear paradigms. The data suggest that fibers passing through the AHN and VMH, and not cells in the MHDC, mediate unconditioned freezing to the predator odor TMT.

  12. The role of oestradiol in sexually dimorphic hypothalamic-pituitary-adrena axis responses to intracerebroventricular ethanol administration in the rat.

    Science.gov (United States)

    Larkin, J W; Binks, S L; Li, Y; Selvage, D

    2010-01-01

    Systemic ethanol (EtOH) administration activates the hypothalamic-pituitary-adrenal (HPA) axis of rats in a sexually dimorphic manner. The present studies tested the role played by the central nervous system (CNS) in this phenomenon. To localise the effects of the drug to the brain, we utilised an experimental paradigm whereby a small, nontoxic amount of the drug was delivered via intracerebroventricular (i.c.v.) injection. EtoH administered i.c.v. rapidly diffuses throughout the cerebrospinal fluid and brain, and does not cause neuronal damage or have any long-term physiological or behavioural effects. Experimental groups included intact males, intact cycling females, and ovariectomised (OVX) animals with or without replacement oestradiol (E(2)). Intracerebroventricular EtOH-induced HPA hormonal activation was determined by measuring plasma adrenocorticotrophin (ACTH) levels. Activation of brain areas that both regulate HPA function and are responsive to gonadal hormones was determined using expression of the transcription factor c-fos (Fos) as a marker of neuronal activity. We observed sex- and oestrous cycle- dependent differences in HPA activation by EtOH as measured by both these parameters. ACTH secretion was highest in females in pro-oestrus or oestrus, just prior to or after the endogenous peak of E(2), as was Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and the locus coreuleus (LC) of the brainstem. In OVX animals, E(2) replacement caused an increase in PVN and LC Fos expression in response to i.c.v. EtOH compared to OVX controls, but a decrease in ACTH secretion. Taken together, these results indicate that at the level of the CNS, EtOH stimulates HPA activity more robustly at times when the effects of E(2) are high, but that E(2) alone is not responsible for this effect. The data further suggest that the LC plays an important role in the circuitry, which appears to be different from that activated following the systemic

  13. Different critical perinatal periods and hypothalamic sites of oestradiol action in the defeminisation of luteinising hormone surge and lordosis capacity in the rat.

    Science.gov (United States)

    Sakakibara, M; Deura, C; Minabe, S; Iwata, Y; Uenoyama, Y; Maeda, K-I; Tsukamura, H

    2013-03-01

    Female rats show a gonadotrophin-releasing hormone (GnRH)/luteinising hormone (LH) surge in the presence of a preovulatory level of oestrogen, whereas males do not because of brain defeminisation during the developmental period by perinatal oestrogen converted from androgen. The present study aimed to identify the site(s) of oestrogen action and the critical period for defeminising the mechanism regulating the GnRH/LH surge. Animals given perinatal treatments, such as steroidal manipulations, brain local implantation of oestradiol (E(2) ) or administration of an NMDA antagonist, were examined for their ability to show an E(2) -induced LH surge at adulthood. Lordosis behaviour was examined to compare the mechanisms defeminising the GnRH/LH surge and sexual behaviour. A single s.c. oestradiol-benzoate administration on either the day before birth (E21), the day of birth (D0) or day 5 (D5) postpartum completely abolished the E(2) -induced LH surge at adulthood in female rats, although the same treatment did not inhibit lordosis. Perinatal castration on E21 or D0 partially rescued the E2-induced LH surge in genetically male rats, whereas castration from E21 to D5 totally rescued lordosis. Neonatal E(2) implantation in the anterior hypothalamus including the anteroventral periventricular nucleus (AVPV)/preoptic area (POA) abolished the E(2) -induced LH surge in female rats, whereas E(2) implantation in the mid and posterior hypothalamic regions had no inhibitory effect on the LH surge. Lordosis was not affected by neonatal E(2) implantation in any hypothalamic regions. In male rats, neonatal NMDA antagonist treatment rescued lordosis but not the LH surge. Taken together, these results suggest that an anterior hypothalamic region such as the AVPV/POA region is a perinatal site of oestrogen action where the GnRH/LH regulating system is defeminised to abolish the oestrogen-induced surge. The mechanism for defeminisation of the GnRH/LH surge system might be different from

  14. Radiometric assay for phenylethanolamine N-methyltransferase and catechol O-methyltransferase in a single tissue sample: application to rat hypothalamic nuclei, pineal gland, and heart

    Energy Technology Data Exchange (ETDEWEB)

    Culman, J.; Torda, T.; Weise, V.K.

    1987-08-01

    A simple and highly sensitive method for simultaneous assay of phenylethanolamine N-methyltransferase (PNMT) and catechol O-methyltransferase (COMT) is described. These enzymes are determined in a single tissue homogenate using S-(methyl-/sup 3/H) adenosyl-L-methionine as methyl donor and sequentially incubating with the substrates phenylethanolamine and epinephrine. The radioactive products of the enzymatic reactions, N-methylphenylethanolamine and metanephrine, are extracted and then separated by thin-layer chromatography. The identity of the reaction products has been established chromatographically and the conditions for both enzymatic reactions in the assay procedure have been defined. Measurement of PNMT activity in the rat pineal gland or in minute fragments of other tissues (e.g., brain nuclei) has not been possible using previously described methods. Activities of PNMT and COMT in the rat pineal gland, various hypothalamic nuclei, and the auricular and ventricular myocardia are herein reported.

  15. Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats.

    Science.gov (United States)

    Buhl, Esben S; Jensen, Thomas Korgaard; Jessen, Niels; Elfving, Betina; Buhl, Christian S; Kristiansen, Steen B; Pold, Rasmus; Solskov, Lasse; Schmitz, Ole; Wegener, Gregers; Lund, Sten; Petersen, Kitt Falck

    2010-05-01

    Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4-5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser(473) phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW (P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion (P < 0.05 vs. Cx), whole body insulin resistance (P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression (P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser(473) phosphorylation. The ESC treatment normalized corticosterone secretion (P < 0.05 vs. LBW), whole body insulin sensitivity (P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression (P < 0.05), and red muscle PKB Ser(473) phosphorylation (P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.

  16. ERK1/2 MAPK signaling in hypothalamic paraventricular nucleus contributes to sympathetic excitation in rats with heart failure after myocardial infarction.

    Science.gov (United States)

    Yu, Yang; Wei, Shun-Guang; Zhang, Zhi-Hua; Weiss, Robert M; Felder, Robert B

    2016-03-15

    Brain MAPK signaling pathways are activated in heart failure (HF) induced by myocardial infarction and contribute to augmented sympathetic nerve activity. We tested whether decreasing ERK1/2 (also known as p44/42 MAPK) signaling in the hypothalamic paraventricular nucleus (PVN), a forebrain source of presympathetic neurons, would reduce the upregulation of sympathoexcitatory mediators in the PVN and augmented sympathetic nerve activity in rats with HF. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce HF, with left ventricular dysfunction confirmed by echocardiography. One week after coronary artery ligation or sham operation, small interfering (si)RNAs targeting ERK1/2 or a nontargeting control siRNA was microinjected bilaterally into the PVN. Experiments were conducted 5-7 days later. Confocal images revealed reduced phosphorylated ERK1/2 immunofluorescence in the PVN of HF rats treated with ERK1/2 siRNAs compared with HF rats treated with control siRNA. Western blot analysis confirmed significant reductions in both total and phosphorylated ERK1/2 in the PVN of HF rats treated with ERK1/2 siRNAs along with reduced expression of renin-angiotensin system components and inflammatory mediators. HF rats treated with ERK1/2 siRNAs also had reduced PVN neuronal excitation (fewer Fos-related antigen-like-immunoreactive neurons), lower plasma norepinephrine levels, and improved peripheral manifestations of HF compared with HF rats treated with control siRNAs. These results demonstrate that ERK1/2 signaling in the PVN plays a pivotal role in mediating sympathetic drive in HF induced by myocardial infarction and may be a novel target for therapeutic intervention.

  17. Activation of heme oxygenase and consequent carbon monoxide formation inhibits the release of arginine vasopressin from rat hypothalamic explants. Molecular linkage between heme catabolism and neuroendocrine function.

    Science.gov (United States)

    Mancuso, C; Kostoglou-Athanassiou, I; Forsling, M L; Grossman, A B; Preziosi, P; Navarra, P; Minotti, G

    1997-10-15

    Heme oxygenase (HO)-catalyzed degradation of cellular heme moieties generates biliverdin and equimolar amounts of carbon monoxide (CO), which has been implicated as a possible modulator of neural function. Technical difficulties preclude direct measurements of CO within intact nervous tissues; hence, alternative procedures are needed to monitor the formation and possible biologic functions of this gas. In the present study rat hypothalamic explants were found to generate 114 +/- 5 or 127 +/- 11 pmol biliverdin/hypothalamus/1 h (n = 3) upon incubation with 1 or 10 microM hemin, respectively. Ten micromolar zinc-protoporphyrin IX (Zn-PP-IX), a known inhibitor of HO, significantly decreased the degradation of 10 microM hemin from 127 +/- 11 to 26 +/- 11 pmol biliverdin/hypothalamus/1 h (n = 3; P tin-mesoporphyrin IX, which is even more selective in inhibiting HO; it was also attenuated in the presence of the gaseous scavenger ferrous hemoglobin. Furthermore, the inhibition of AVP release could be reproduced by omitting hemin and by incubating hypothalami under CO, whereas treatment with biliverdin had no effect. This suggested that the release of AVP was suppressed by HO degradation of hemin, yielding CO as a modulator of hypothalamic function. These observations may be relevant to diseases characterized by inappropriate secretion of AVP and enzymatic disturbances affecting the synthesis of heme and the formation of CO through the HO pathway (e.g., acute intermittent porphyria or lead intoxication).

  18. Regional haemodynamic effects of mu-, delta-, and kappa-opioid agonists microinjected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats.

    Science.gov (United States)

    Bachelard, H; Pître, M

    1995-06-01

    1. The cardiovascular effects of bilateral injection into the hypothalamic paraventricular nuclei of selective mu-, delta-, and kappa-opioid receptor agonists were investigated in conscious, unrestrained Wistar Kyoto rats, chronically instrumented with pulsed Doppler flow probes for measurement of regional haemodynamics. 2. The selective mu-agonist [D-Ala2,MePhe4,Gly5ol]enkephalin (DAMGO), injected bilaterally into the hypothalamic paraventricular nuclei (0.01-1.0 nmol), caused increases in blood pressure, tachycardias, vasoconstriction in renal and superior mesenteric vascular beds and substantial vasodilatation in the hindquarter vascular bed. 3. The administration of increasing doses (0.01-5.0 nmol) of the selective delta-agonist [D-Phe2,5]enkephalin (DPDPE) or the selective kappa-agonist, U50488H into the paraventricular nuclei (PVN) had no significant effect on blood pressure, heart rate, or regional haemodynamics. 4. Together, the present results are further evidence of a role for opioid peptides, especially acting at mu-receptors in the PVN, in the central regulation of the cardiovascular system, whereas a role for opioid peptides, acting at delta- and kappa-receptors in the PVN, seems less obvious from the present results.

  19. Increase of long-term 'diabesity' risk, hyperphagia, and altered hypothalamic neuropeptide expression in neonatally overnourished 'small-for-gestational-age' (SGA rats.

    Directory of Open Access Journals (Sweden)

    Karen Schellong

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

  20. Role of the ventromedial nucleus of the thalamus in motor behaviour--I. Effects of focal injections of drugs.

    Science.gov (United States)

    Starr, M S; Summerhayes, M

    1983-12-01

    An assortment of drugs was injected into one or both ventromedial nuclei of the thalamus, to see how these influenced stereotypy, locomotion and posture in spontaneously behaving and actively rotating rats. Unilateral intrathalamic muscimol promoted weak ipsiversive circling, while bilateral treatment gave catalepsy. Similar injections of 4-amino-hex-5-enoic acid, which inhibits gamma-aminobutyrate metabolism, raised gamma-aminobutyrate levels in the ventromedial nuclei more than three-fold yet had none of these behavioural effects. The indirectly acting gamma-aminobutyrate agonists flurazepam and cis-1,3-aminocyclohexane carboxylic acid had little effect on posture and locomotion and, like muscimol and 4-amino-hex-5-enoic acid, elicited only very weak stereotypies. Procaine behaved like the gamma-aminobutyrate antagonist bicuculline, provoking vigorous locomotor hyperactivity and teeth chattering if given uni- or bilaterally. Pretreatment of one ventromedial nucleus with muscimol or 4-amino-hex-5-enoic acid, and to a lesser extent flurazepam or cis- 1,3-aminocyclohexane carboxylic acid, gave rise to pronounced ipsilateral asymmetries when combined with a large systemic dose of apomorphine. Contraversive rotations were initiated by unilateral stereotaxic injection of muscimol into the substantia nigra pars reticulata, or with apomorphine from the supersensitive striatum in unilaterally 6-hydroxydopamine lesioned rats. Drug treatments in the ipsilateral ventromedial nucleus showed a similar rank order of potency at inhibiting these circling behaviours, seemingly by reducing apomorphine-induced posture and muscimol-induced hypermotility. The suppression of circling by muscimol in these tests was highlighted by introducing the compound into the ventromedial nucleus at the height of circling activity. Both types of circling stimulus lost the capacity to increase locomotion, but still caused head turning and stereotypy in rats made cataleptic with bilateral ventromedial

  1. Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

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    Jong-Ho Lee

    2014-06-01

    Full Text Available BackgroundThis study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF during adolescence on the adverse behavioral outcome of neonatal maternal separation.MethodsMale Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS or left undisturbed (nonhandled, NH. Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF. Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay.ResultsDaily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it.ConclusionProlonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA axis.

  2. Inhibition of dehydration-induced water intake by glucocorticoids is associated with activation of hypothalamic natriuretic peptide receptor-A in rat.

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    Chao Liu

    Full Text Available Atrial natriuretic peptide (ANP provides a potent defense mechanism against volume overload in mammals. Its primary receptor, natriuretic peptide receptor-A (NPR-A, is localized mostly in the kidney, but also is found in hypothalamic areas involved in body fluid volume regulation. Acute glucocorticoid administration produces potent diuresis and natriuresis, possibly by acting in the renal natriuretic peptide system. However, chronic glucocorticoid administration attenuates renal water and sodium excretion. The precise mechanism underlying this paradoxical phenomenon is unclear. We assume that chronic glucocorticoid administration may activate natriuretic peptide system in hypothalamus, and cause volume depletion by inhibiting dehydration-induced water intake. Volume depletion, in turn, compromises renal water excretion. To test this postulation, we determined the effect of dexamethasone on dehydration-induced water intake and assessed the expression of NPR-A in the hypothalamus. The rats were deprived of water for 24 hours to have dehydrated status. Prior to free access to water, the water-deprived rats were pretreated with dexamethasone or vehicle. Urinary volume and water intake were monitored. We found that dexamethasone pretreatment not only produced potent diuresis, but dramatically inhibited the dehydration-induced water intake. Western blotting analysis showed the expression of NPR-A in the hypothalamus was dramatically upregulated by dexamethasone. Consequently, cyclic guanosine monophosphate (the second messenger for the ANP content in the hypothalamus was remarkably increased. The inhibitory effect of dexamethasone on water intake presented in a time- and dose-dependent manner, which emerged at least after 18-hour dexamethasone pretreatment. This effect was glucocorticoid receptor (GR mediated and was abolished by GR antagonist RU486. These results indicated a possible physiologic role for glucocorticoids in the hypothalamic control of

  3. Effects of ghrelin on Kisspeptin mRNA expression in the hypothalamic medial preoptic area and pulsatile luteinising hormone secretion in the female rat.

    Science.gov (United States)

    Forbes, Sarah; Li, Xiao Feng; Kinsey-Jones, James; O'Byrne, Kevin

    2009-08-28

    The orexigenic gut peptide ghrelin negatively modulates the hypothalamic-pituitary-gonadal (HPG) axis. Hyperghrelinaemia results during negative energy balance, a state often associated with delayed puberty and disrupted fertility, whilst exogenous ghrelin suppresses pulsatile luteinising hormone (LH) secretion. The recent identification of kisspeptin (Kiss1) and its G protein-coupled receptor (GPR)54 (Kiss1r) as an essential component of the HPG axis controlling gonadotrophin secretion raises the possibility that kisspeptin-Kiss1r signalling may play a critical role in the transduction of ghrelin-induced suppression of LH. Ovariectomised oestrogen-replaced rats were implanted with intravenous catheters and blood samples collected for detection of LH pulses prior to and after intravenous administration of ghrelin (3nM/250 microl) or saline (250 microl) during ad libitum feeding or after overnight fasting. Quantitative RT-PCR was used to determine Kiss1 and Kiss1r mRNA levels in brain punches of the key hypothalamic sites regulating gonadotrophin secretion, the medial preoptic area (mPOA) and arcuate nucleus (ARC), collected 6h following administration of ghrelin. Ghrelin significantly lowered LH pulse frequency in fed rats, an effect significantly enhanced by food deprivation. Fasting, ghrelin or their combination down-regulated Kiss1, without affecting Kiss1r, expression in the mPOA, and affected the expression of neither in the ARC. Considering the pivotal role for kisspeptin signalling in the activation of the HPG axis, the ability of ghrelin to down-regulate Kiss1 expression in mPOA may be a contributing factor in ghrelin-related suppression of pulsatile LH secretion.

  4. Variations in Phase and Amplitude of Rhythmic Clock Gene Expression across Prefrontal Cortex, Hippocampus, Amygdala, and Hypothalamic Paraventricular and Suprachiasmatic Nuclei of Male and Female Rats.

    Science.gov (United States)

    Chun, Lauren E; Woodruff, Elizabeth R; Morton, Sarah; Hinds, Laura R; Spencer, Robert L

    2015-10-01

    The molecular circadian clock is a self-regulating transcription/translation cycle of positive (Bmal1, Clock/Npas2) and negative (Per1,2,3, Cry1,2) regulatory components. While the molecular clock has been well characterized in the body's master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), only a few studies have examined both the positive and negative clock components in extra-SCN brain tissue. Furthermore, there has yet to be a direct comparison of male and female clock gene expression in the brain. This comparison is warranted, as there are sex differences in circadian functioning and disorders associated with disrupted clock gene expression. This study examined basal clock gene expression (Per1, Per2, Bmal1 mRNA) in the SCN, prefrontal cortex (PFC), rostral agranular insula, hypothalamic paraventricular nucleus (PVN), amygdala, and hippocampus of male and female rats at 4-h intervals throughout a 12:12 h light:dark cycle. There was a significant rhythm of Per1, Per2, and Bmal1 in the SCN, PFC, insula, PVN, subregions of the hippocampus, and amygdala with a 24-h period, suggesting the importance of an oscillating molecular clock in extra-SCN brain regions. There were 3 distinct clock gene expression profiles across the brain regions, indicative of diversity among brain clocks. Although, generally, the clock gene expression profiles were similar between male and female rats, there were some sex differences in the robustness of clock gene expression (e.g., females had fewer robust rhythms in the medial PFC, more robust rhythms in the hippocampus, and a greater mesor in the medial amygdala). Furthermore, females with a regular estrous cycle had attenuated aggregate rhythms in clock gene expression in the PFC compared with noncycling females. This suggests that gonadal hormones may modulate the expression of the molecular clock.

  5. Effects of black adzuki bean (Vigna angularis, Geomguseul extract on body composition and hypothalamic neuropeptide expression in rats fed a high-fat diet

    Directory of Open Access Journals (Sweden)

    Mina Kim

    2015-10-01

    Full Text Available Background: Obesity is often considered to result from either excessive food intake or insufficient physical activity. Adzuki beans have been evaluated as potential remedies for various health conditions, and recent studies have reported their effects on the regulation of lipid metabolism, but it remains to be determined whether they may be effective in overcoming obesity by regulating appetite and satiety. Objective: This study investigated the effect of black adzuki bean (BAB extract on body composition and hypothalamic neuropeptide expression in Sprague Dawley rats (Rattus norvegicus fed a high-fat diet. Design: The rats were fed for 8 weeks with a control diet containing 10 kcal% from fat (CD, a high-fat diet containing 60 kcal% from fat (HD, or a high-fat diet with 1% or 2% freeze-dried ethanolic extract powder of BAB (BAB-1 and BAB-2. Results: The body weights and epididymal fat weights were significantly reduced and the serum lipid profiles were improved in the group fed the diet containing BAB compared to the HD group. The expression of AGRP mRNA significantly decreased in the BAB groups, and treatment with BAB-2 resulted in a marked induction of the mRNA expression of POMC and CART, which are anorexigenic neuropeptides that suppress food intake. Furthermore, mRNA expression levels of ObRb, a gene related to leptin sensitivity in the hypothalamus, were significantly higher in the BAB groups than in the HD group. Conclusions: These results suggest that supplementation with BAB has a significant effect on body weight via regulation of hypothalamic neuropeptides.

  6. Isolation of the gene and hypothalamic of cDNA for the common precursor of gonadotropin-releasing hormone and prolactin release-inhibiting factor in human and rat

    Energy Technology Data Exchange (ETDEWEB)

    Adelman, J.P.; Mason, A.J.; Hayflick, J.S.; Seeburg, P.H.

    1986-01-01

    Cloned cDNAs encoding the precursor protein for gonadotropin-releasing hormone (Gn-RH) and prolactin release-inhibiting factor (PIF) were isolated from libraries derived from human and rat hypothalamic mRNA. Nucleotide sequence analyses predict precursor proteins of 92 amino acids for both species and show identity between the human placental and human hypothalamic precursor proteins. Whereas the Gn-RH peptide structure is completely conserved in human and rat, the PIF domain of the precursor displays 70% interspecies homology. Genomic analyses revealed the presence of a single Gn-RH-PIF gene in human and rat containing sequences corresponding to the cDNA distributed across four exons.

  7. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xin-Ai; Jia, Lin-Lin [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Meng [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Yuan, Zu-Yi [Department of Cardiovascular Medicine, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Guo, Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Li, Hui-Hua [Key Laboratory of Remodeling-related Cardiovascular Diseases, Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Liu, Hao, E-mail: haoliu75@163.com [Department of Neurosurgery, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-11-15

    We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

  8. Impact of neonatal exposure to the ERalpha agonist PPT, bisphenol-A or phytoestrogens on hypothalamic kisspeptin fiber density in male and female rats.

    Science.gov (United States)

    Patisaul, Heather B; Todd, Karina L; Mickens, Jillian A; Adewale, Heather B

    2009-05-01

    Neonatal exposure to endocrine disrupting compounds (EDCs) can impair reproductive physiology, but the specific mechanisms by which this occurs remain largely unknown. Growing evidence suggests that kisspeptin (KISS) neurons play a significant role in the regulation of pubertal onset and ovulation, therefore disruption of KISS signaling could be a mechanism by which EDCs impair reproductive maturation and function. We have previously demonstrated that neonatal exposure to phytoestrogens decreases KISS fiber density in the anterior hypothalamus of female rats, an effect which was associated with early persistent estrus and the impaired activation gonadotropin releasing hormone (GnRH) neurons. The goals of the present study were to (1) determine if an ERalpha selective agonist (PPT) or bisphenol-A (BPA) could produce similar effects on hypothalamic KISS content in female rats and (2) to determine if male KISS fiber density was also vulnerable to disruption by EDCs. We first examined the effects of neonatal exposure to PPT, a low (50 microg/kg bw) BPA dose, and a high (50 mg/kg bw) BPA dose on KISS immunoreactivity (-ir) in the anterior ventral periventricular (AVPV) and arcuate (ARC) nuclei of adult female rats, using estradiol benzoate (EB) and a sesame oil vehicle as controls. AVPV KISS-ir, following ovariectomy (OVX) and hormone priming, was significantly lower in the EB and PPT groups but not the BPA groups. ARC KISS-ir levels were significantly diminished in the EB and high dose BPA groups, and there was a nonsignificant trend for lower KISS-ir in the PPT group. We next examined effects of neonatal exposure to a low (50 microg/kg bw) dose of BPA and the phytoestrogens genistein (GEN) and equol (EQ) on KISS-ir in the AVPV and ARC of adult male rats, using OVX females as an additional control group. None of the compounds affected KISS-ir in the male hypothalamus. Our results suggest that the organization of hypothalamic KISS fibers may be vulnerable to disruption

  9. Cafeteria diet differentially alters the expression of feeding-related genes through DNA methylation mechanisms in individual hypothalamic nuclei.

    Science.gov (United States)

    Lazzarino, Gisela Paola; Andreoli, María Florencia; Rossetti, María Florencia; Stoker, Cora; Tschopp, María Virgina; Luque, Enrique Hugo; Ramos, Jorge Guillermo

    2017-07-15

    We evaluated the effect of cafeteria diet (CAF) on the mRNA levels and DNA methylation state of feeding-related neuropeptides, and neurosteroidogenic enzymes in discrete hypothalamic nuclei. Besides, the expression of steroid hormone receptors was analyzed. Female rats fed with CAF from weaning increased their energy intake, body weight, and fat depots, but did not develop metabolic syndrome. The increase in energy intake was related to an orexigenic signal of paraventricular (PVN) and ventromedial (VMN) nuclei, given principally by upregulation of AgRP and NPY. This was mildly counteracted by the arcuate nucleus, with decreased AgRP expression and increased POMC and kisspeptin expression. CAF altered the transcription of neurosteroidogenic enzymes in PVN and VMN, and epigenetic mechanisms associated with differential promoter methylation were involved. The changes observed in the hypothalamic nuclei studied could add information about their differential role in food intake control and how their action is disrupted in obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Neurochemical and behavioral analyses of the lateral hypothalamic syndrome: a look back.

    Science.gov (United States)

    Stricker, Edward M

    2012-06-01

    Philip Teitelbaum is one of the great physiological psychologists of his generation. His early research clarified key issues regarding the effects of electrolytic lesions of the ventromedial or ventrolateral hypothalamus on food intake in rats, a subject of paramount interest during the 1950s and 1960s. Perhaps best known were his extensive studies of the lateral hypothalamic syndrome in rats, which focused on the complex and changing array of symptoms after experimental brain damage. It soon became clear from later work that his research interests were not in the brain's control of food intake but in the effects of lesions to fragment behavior and thereby allow investigators to view its components. He was the foremost proponent of the use of exquisite behavioral analysis to reveal details in movement that allowed insights into brain function, and that approach - old fashioned physiological psychology made modern and at its finest - has infiltrated the entire field of experimental psychology, including studies of ingestive behavior, even while the new field of behavioral neuroscience emerged. He extended his analytic approach to neurological issues such as autism in humans, a promising arena that fully occupied his attention during the later phases of his career. But his influence on his scientific colleagues went well beyond his careful and powerful thinking; his articles and books have been models of clarity and concision. I write in behalf of a grateful field to salute his many great contributions.

  11. Intestinal fatty acid infusion modulates food preference as well as calorie intake via the vagal nerve and midbrain-hypothalamic neural pathways in rats.

    Science.gov (United States)

    Ogawa, Nobuya; Ito, Makoto; Yamaguchi, Hideki; Shiuchi, Tetsuya; Okamoto, Shiki; Wakitani, Korekiyo; Minokoshi, Yasuhiko; Nakazato, Masamitsu

    2012-09-01

    The intestine plays important roles in the regulation of feeding behavior by sensing macronutrients. Intestinal fatty acids strongly suppress food intake, but little is known about whether intestinal fatty acids affect food preference. We investigated the effects of jejunal fatty acids infusion on food preference by conducting two-diet choice experiments in rats fed a high-fat diet (HFD) and a high-carbohydrate diet (HCD). Jejunal linoleic acid (18:2) infusion reduced HFD intake dose-dependently, while HCD intake increased with the middle dose of the infusion we examined (100 μL/h) and reduced to the control level with the higher doses (150 and 200 μL/h). α-Linolenic acid (18:3), but not caprylic acid (8:0), altered the food preference and total calorie intake in the same manner as linoleic acid. Linoleic acid infusion dose-dependently increased plasma glucagon-like peptide-1, peptide YY and cholecystokinin levels, but not ghrelin levels. Subdiaphragmatic vagotomy or midbrain transection prevented the change in food preference and total calorie intake by linoleic acid infusion. Jejunal linoleic acid infusion increased norepinephrine turnover in the paraventricular hypothalamic nucleus, while intracerebroventricular injection of idazoxan, an α2-adrenergic receptor (AR) antagonist, suppressed the increased HCD intake, but did not affect the decreased HFD intake. These findings indicated that intestinal long-chain fatty acids modulated food preference as well as total calorie intake via the vagal nerve and midbrain-hypothalamic neural pathways. The effects of the α2-AR antagonist in the brain suggested that the brain distinctly controlled HCD and HFD intake in response to jejunal linoleic acid infusion. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Opposing roles of the nucleus accumbens and anterior lateral hypothalamic area in the control of sexual behaviour in the male rat.

    Science.gov (United States)

    Kippin, Tod E; Sotiropoulos, Veneta; Badih, Julia; Pfaus, James G

    2004-02-01

    Opposing roles have been implicated for the nucleus accumbens (NAc) and anterior portion of the lateral hypothalamic area (aLHA) in the regulation of sexual behaviour in male rats based on in vivo neurochemical correlates. The present study provides functional evidence supporting this hypothesis by examining the effects of lesions to these structures on copulation, noncontact erection and receptive female preference. Sexually naïve male Long-Evans rats received either bilateral 1.0- micro L injections of NMDA (10 micro g/ micro L/side) or vehicle (shams) into either the aLHA or the NAc. During repeated tests of copulation most of the sham-lesioned males, but few of the aLHA-lesioned and NAc-lesioned males, copulated to ejaculation. Most of the NAc-lesioned males also failed to intromit, whereas the majority of the aLHA-lesioned males intromitted repeatedly. During exposure to an inaccessible receptive female behind a wire-mesh screen, aLHA-lesioned males displayed facilitation of noncontact erections, whereas NAc-lesioned males displayed impaired noncontact erections. Conversely, during simultaneous exposure to inaccessible receptive and nonreceptive females in different compartments, all males spent more time in the proximity of the receptive female. These findings indicate that the aLHA plays an inhibitory role in the regulation of sexual arousal and an excitatory role in the regulation of ejaculation. Conversely, the NAc plays an excitatory role in the regulation in sexual arousal.

  13. [Effect of the intermittent hypoxic training on the functioning of peptidergic neurons of the paraventricular hypothalamic nucleus and brain stem neurons in rats].

    Science.gov (United States)

    Abramov, A V

    1998-03-01

    Internittent hypoxic training (IHT) increased the quantity and secretory activity of peptidergic neurons of the paraventricular hypothalamic nucleus (PHN) and activated neurons of the dorsal motor nucleus of n.vagus. These structures seem to take part in realisation of the IHT activating effect on condition of the pancreatic delta-cells. The effect involves insulin-stimulating and insuloprotective effects realised via hypothalamic and neuro-conducting ways of regulation of the endocrine pancreas with a direct participation of hypothalamic neuropeptides.

  14. Circadian rhythms of PERIOD1 expression in the dorsomedial hypothalamic nucleus in the absence of entrained food-anticipatory activity rhythms in rats.

    Science.gov (United States)

    Verwey, Michael; Lam, Germain Y M; Amir, Shimon

    2009-06-01

    When food availability is restricted to a single time of day, circadian rhythms of behavior and physiology in rodents shift to anticipate the predictable time of food arrival. It has been hypothesized that certain food-anticipatory rhythms are linked to the induction and entrainment of rhythms in clock gene expression in the dorsomedial hypothalamic nucleus (DMH), a putative food-entrained circadian oscillator. To study this concept further, we made food availability unpredictable by presenting the meal at a random time each day (variable restricted feeding, VRF), either during the day, night or throughout the 24-h cycle. Wheel running activity and the expression of the clock protein, Period1 (PER1), in the DMH and the suprachiasmatic nucleus (SCN) were assessed. Rats exhibited increased levels of activity during the portion of the day when food was randomly presented but, as expected, failed to entrain anticipatory wheel running activity to a single time of day. PER1 expression in the SCN was unchanged by VRF schedules. In the DMH, PER1 expression became rhythmic, peaking at opposite times of day in rats fed only during the day or during the night. In rats fed randomly throughout the entire 24-h cycle, PER1 expression in the DMH remained arrhythmic, but was elevated. These results demonstrate that VRF schedules confined to the day or night can induce circadian rhythms of clock gene expression in the DMH. Such feeding schedules cannot entrain behavioral rhythms, thereby showing that food-entrainment of behavior and circadian rhythms of clock gene expression in the DMH are dissociable.

  15. Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition.

    Science.gov (United States)

    Wolf, Richard C; Philippi, Carissa L; Motzkin, Julian C; Baskaya, Mustafa K; Koenigs, Michael

    2014-06-01

    The ventromedial prefrontal cortex is known to play a crucial role in regulating human social and emotional behaviour, yet the precise mechanisms by which it subserves this broad function remain unclear. Whereas previous neuropsychological studies have largely focused on the role of the ventromedial prefrontal cortex in higher-order deliberative processes related to valuation and decision-making, here we test whether ventromedial prefrontal cortex may also be critical for more basic aspects of orienting attention to socially and emotionally meaningful stimuli. Using eye tracking during a test of facial emotion recognition in a sample of lesion patients, we show that bilateral ventromedial prefrontal cortex damage impairs visual attention to the eye regions of faces, particularly for fearful faces. This finding demonstrates a heretofore unrecognized function of the ventromedial prefrontal cortex-the basic attentional process of controlling eye movements to faces expressing emotion.

  16. Blunted hypothalamic ghrelin signaling reduces diet intake in rats fed a low-protein diet in late pregnancy.

    Science.gov (United States)

    Gao, Haijun; Sisley, Stephanie; Yallampalli, Chandra

    2015-12-01

    Diet intake in pregnant rats fed a low-protein (LP) diet was significantly reduced during late pregnancy despite elevated plasma levels of ghrelin. In this study, we hypothesized that ghrelin signaling in the hypothalamus is blunted under a low-protein diet condition and therefore, it does not stimulate diet intake during late pregnancy. Female Sprague-Dawley rats were fed a normal (CT) or LP diet from Day 1 of pregnancy. On Day 21, 0.5 μg ghrelin was given into the third ventricle (ICV). Diet and water intake at 30, 60, and 120 min after ICV injection was measured. Hypothalami were dissected and analyzed for expression of genes related to appetite regulation (Npy, Agrp, Pomc and Cart) and phosphorylation of AMPK and ACC proteins (downstream proteins of ghrelin receptor activation). Results include: In response to ICV injection of ghrelin, (1) diet intake was significantly lower in LP compared to CT rats; (2) water intake was not affected in LP rats; (3) expression of Npy and Agrp, but not Pomc and Cart, were higher in the hypothalamus of LP compared to CT rats; (4) the abundance of phosphorylated AMPK and the ratio of phosphorylated to total AMPK, but not the abundance of total AMPK, were lower in LP compared to CT rats; (5) the abundance of phosphorylated ACC, but not total ACC, was lower in LP rats. These findings suggest that blunted ghrelin signaling in the hypothalamus of pregnant rats fed a LP diet leads to reduced diet intake and exacerbates gestational protein insufficiency.

  17. Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats.

    Science.gov (United States)

    Landry, Glenn J; Kent, Brianne A; Patton, Danica F; Jaholkowski, Mark; Marchant, Elliott G; Mistlberger, Ralph E

    2011-01-01

    The dorsomedial hypothalamus (DMH) is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO) have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (T(b)) rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and T(b) rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and T(b) rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep.

  18. Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats.

    Directory of Open Access Journals (Sweden)

    Glenn J Landry

    Full Text Available The dorsomedial hypothalamus (DMH is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (T(b rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and T(b rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and T(b rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep.

  19. Reciprocal connections between CART-immunoreactive, hypothalamic paraventricular neurons and serotonergic dorsal raphe cells in the rat: Light microscopic study.

    Science.gov (United States)

    Lee, Ji S; Lee, Hyun S

    2014-04-29

    Based on the overlapping physiological roles of cocaine- and amphetamine-regulated transcript (CART) peptides and serotonin, the present study examined the anatomical connection between the hypothalamic paraventricular nucleus (PVN) and the dorsal raphe (DR). The first series of experiments were performed to investigate descending projections from the CART-immunoreactive (CART-ir) PVN to serotonergic DR cells. CART-ir varicosities made contact with serotonergic DR neurons. An anterograde tracing study revealed that varicosities originating from the PVN formed close appositions to serotonergic neuronal profiles along the entire rostro-caudal extent of the DR. A retrograde study demonstrated that CART neurons projecting to the DR were mainly localized in the caudal parvicellular PVN, comprising approximately 3.0%±0.4% (n=8) of total CART cells. A second series of experiments was performed to investigate ascending projections from the DR to CART-ir PVN cells. Serotonin transporter-ir boutons made contact with CART-ir PVN neurons. Anterograde tracing revealed that varicosities originating from the DR formed close appositions to CART-ir PVN cells. Retrograde examination demonstrated that serotonergic neurons projecting to the parvicellular PVN were located along the entire rostro-caudal extent of the DR. The present observation provided an anatomical basis for accumulating evidence in the literature that suggests a functional interaction between the CART and serotonin systems during the regulation of energy balance, emotional behavior, and arousal.

  20. Involvement of hypothalamic cyclooxygenase-2, interleukin-1β and melanocortin in the development of docetaxel-induced anorexia in rats.

    Science.gov (United States)

    Yamamoto, Kouichi; Asano, Keiko; Ito, Yui; Matsukawa, Naoki; Kim, Seikou; Yamatodani, Atsushi

    2012-12-16

    Docetaxel, a taxane derivative, is frequently used for the treatment of advanced breast cancer, non-small cell lung cancer, and metastatic prostate cancer. Clinical reports demonstrated that docetaxel-based chemotherapy often induces anorexia, but the etiology is not completely understood. To elucidate possible mechanisms, we investigated the involvement of central interleukin (IL)-1β, cyclooxygenase (COX)-2, and pro-opiomelanocortin (POMC) in the development of docetaxel-induced anorexia in rats. Rats received docetaxel (10mg/kg, i.p.) with or without pretreatment with selective COX-2 inhibitors, NS-398 (10 and 30 mg/kg, i.g.) or celecoxib (10 and 30 mg/kg, i.g.), and a non-selective COX inhibitor, indomethacin (10mg/kg, i.g.), then food intake was monitored for 24h after administration. We also examined expression of IL-1β, COX-2, and POMC mRNA in hypothalamus of docetaxel-treated rats and the effect of a COX-2 inhibitor on docetaxel-induced POMC mRNA expression. Food consumption in rats was significantly decreased 24h after administration of docetaxel and anorexia was partially reversed by all COX inhibitors. Administration of docetaxel increased IL-1β, COX-2, and POMC mRNA expression in the hypothalamus of rats. The time required to increase these gene expressions was comparable to the latency period of docetaxel-induced anorexia in rats. In addition, pretreatment with COX-2 inhibitors suppressed docetaxel-induced expression of POMC mRNA. These results suggest that IL-1β and COX-2 mRNA expression and subsequent activation of POMC in the hypothalamus may contribute to the development of docetaxel-induced anorexia in rats. Copyright © 2012. Published by Elsevier Ireland Ltd.

  1. The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats.

    Science.gov (United States)

    Merlo, Eduardo; Podratz, Priscila L; Sena, Gabriela C; de Araújo, Julia F P; Lima, Leandro C F; Alves, Izabela S S; Gama-de-Souza, Letícia N; Pelição, Renan; Rodrigues, Lívia C M; Brandão, Poliane A A; Carneiro, Maria T W D; Pires, Rita G W; Martins-Silva, Cristina; Alarcon, Tamara A; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

    2016-08-01

    Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.

  2. Intraperitoneal injection of neuropeptide Y (NPY) alters neurotrophin rat hypothalamic levels: Implications for NPY potential role in stress-related disorders.

    Science.gov (United States)

    Gelfo, Francesca; De Bartolo, Paola; Tirassa, Paola; Croce, Nicoletta; Caltagirone, Carlo; Petrosini, Laura; Angelucci, Francesco

    2011-06-01

    Neuropeptide Y (NPY) is a 36-amino acid peptide which exerts several regulatory actions within peripheral and central nervous systems. Among NPY actions preclinical and clinical data have suggested that the anxiolytic and antidepressant actions of NPY may be related to its antagonist action on the hypothalamic-pituitary-adrenal (HPA) axis. The neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are proteins involved in the growth, survival and function of neurons. In addition to this, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has been proposed. To characterize the effect of NPY on the production of neurotrophins in the hypothalamus we exposed young adult rats to NPY intraperitoneal administration for three consecutive days and then evaluated BDNF and NGF synthesis in this brain region. We found that NPY treatment decreased BDNF and increased NGF production in the hypothalamus. Given the role of neurotrophins in the hypothalamus, these findings, although preliminary, provide evidence for a role of NPY as inhibitor of HPA axis and support the idea that NPY might be involved in pathologies characterized by HPA axis dysfunctions.

  3. The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamic-pituitary-adrenal axis activity in female rats

    Science.gov (United States)

    Švob Štrac, Dubravka; Muck-Šeler, Dorotea; Pivac, Nela

    2012-01-01

    Aim To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity. Methods Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α2-adrenoreceptor agonist), yohimbine (α2-adrenoreceptor antagonist), alpha-methyl-p-tyrosine (α-MPT, an inhibitor of catecholamine synthesis), or reserpine (a catecholamine depleting drug) and yohimbine. Results Diazepam administered in a dose of 2.0 mg/kg suppressed basal HPA axis activity, ie, decreased plasma corticosterone and ACTH levels. Pretreatment with clonidine or yohimbine failed to affect basal plasma corticosterone and ACTH concentrations, but abolished diazepam-induced inhibition of the HPA axis activity. Pretreatment with α-MPT, or with a combination of reserpine and yohimbine, increased plasma corticosterone and ACTH levels and prevented diazepam-induced inhibition of the HPA axis activity. Conclusion The results suggest that α2-adrenoreceptors activity, as well as intact presynaptic noradrenergic function, are required for the suppressive effect of diazepam on the HPA axis activity. PMID:22661134

  4. [Effects of hypothalamic microinjections of 6-hydroxydopamine (6-OHDA) on estral cycle and morphology of the genital tract in the female rat (author's transl)].

    Science.gov (United States)

    Sala, M A; Oteui, J T; Benedetti, W I

    1975-01-01

    To determine whether central catecholaminergic pathways are involved in the neural contral of gonadotrophin secretion, they were interrupted at the hypothalamic level by microinjections of 6-hydroxydopamine (6-OHDA). The effects on ovulation, estral cycle and ovarian and uterine histology were studied. Microinjections of 50 mug of 6-OHDA hydrobromyde were made bilaterally into the anterolateral hypothalamus in a group of rats. Another group was injected with 25 mug of 6-OHDA, while a control group recieved an equivalent volume (5 mul) of saline with ascorbic acid. Animals injected with 50 mug of 6-OHDA showed blockade of ovulation, vaginal cytology characteristics of persistent estrous, polyfollicular ovaries and enlarged uteri with hypertrophic endometrial glands. In the group injected with 25 mug, similiar effects were demonstrated, but the number of affected animals was smaller than that in the 50 mug group. Control animals dit not show modifications, either in estral cycle or in ovarian and uterine histology. These results suggest that 6-OHDA injected into the anterolateral hypothalmus interferes with catecholaminergic pathways that participate in the neural control of ovulation.

  5. Centrally Applied Somatostatin Inhibits the Estrogen-Induced Luteinizing Hormone Surge via Hypothalamic Gonadotropin-Releasing Hormone Cell Activation in Female Rats

    NARCIS (Netherlands)

    Vugt, van H.H.; Swarts, J.J.M.; Heijning, van de H.J.M.; Beek, van der E.M.

    2004-01-01

    Overexpression of growth hormone (GH) as well as GH-deficiency dramatically impairs reproductive function. Decreased reproductive function as a result of altered GH release is, at least partially, due to changes at the hypothalamic-pituitary level. We hypothesize that hypothalamic somatostatin (SOM)

  6. Immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitary-adrenal axis in adult and adolescent rats

    Science.gov (United States)

    ALLEN, Camryn D.; LEE, Soon; KOOB, George F.; RIVIER, Catherine

    2011-01-01

    Alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Part of this influence is likely exerted directly at the level of the corticotropin-releasing factor (CRF) gene, but intermediates may also play a role. Here we review the effect of alcohol on this axis, provide new data on the effects of binge drinking during adolescence, and argue for a role of catecholaminergic circuits. Indeed, acute injection of this drug activates brain stem adrenergic and noradrenergic circuits, and their lesion, or blockade of α1 adrenergic receptors significantly blunts alcohol-induced ACTH release. As alcohol can influence the HPA axis even once discontinued, and alcohol consumption in young people is associated with increased adult drug abuse (a phenomenon possibly mediated by the HPA axis), we determined whether alcohol consumption during adolescence modified this axis. The number of CRF-immunoreactive (ir) cells/section was significantly decreased in the central nucleus of the amygdala of adolescent self-administering binge-drinking animals, compared to controls. When another group of adolescent binge-drinking rats was administered alcohol in adulthood, the number of colocalized c-fos-ir and PNMT-ir cells/brain stem section in the C3 area was significantly decreased, compared to controls. As the HPA axis response to alcohol is blunted in adult rats exposed to alcohol vapors during adolescence, a phenomenon which was not observed in our model of self-administration, it is possible that the blood alcohol levels achieved in various models play a role in the long-term consequences of exposure to alcohol early in life. Collectively, these results suggest an important role of brain catecholamines in modulating the short- and long-term consequences of alcohol administration. PMID:21300146

  7. Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats.

    Directory of Open Access Journals (Sweden)

    Yi-Chun Loraine Tung

    Full Text Available Sequence variants in the first intron of FTO are strongly associated with human obesity and human carriers of the risk alleles show evidence for increased appetite and food intake. Mice globally lacking Fto display a complex phenotype characterised by both increased energy expenditure and increased food intake. The site of action of FTO on energy balance is unclear. Fasting reduces levels of Fto mRNA in the arcuate nucleus (ARC of the hypothalamus, a site where Fto expression is particularly high. In this study, we have extended this nutritional link by demonstrating that consumption of a high fat diet (45% results in a 2.5 fold increase in Arc Fto expression. We have further explored the role of hypothalamic Fto in the control of food intake by using stereotactic injections coupled with AAV technology to bi-directionally modulate Fto expression. An over expression of Fto protein by 2.5-fold in the ARC results in a 14% decrease in average daily food intake in the first week. In contrast, knocking down Arc Fto expression by 40% increases food intake by 16%. mRNA levels of Agrp, Pomc and Npy, ARC-expressed genes classically associated with the control of food intake, were not affected by the manipulation of Fto expression. However, over expression of Fto resulted in a 4-fold increase in the mRNA levels of Stat3, a signalling molecule critical for leptin receptor signalling, suggesting a possible candidate for the mediation of Fto's actions. These data provide further support for the notion that FTO itself can influence key components of energy balance, and is therefore a strong candidate for the mediation of the robust association between FTO intronic variants and adiposity. Importantly, this provide the first indication that selective alteration of FTO levels in the hypothalamus can influence food intake, a finding consistent with the reported effects of FTO alleles on appetite and food intake in man.

  8. Hypothalamic Norepinephrine Mediates Acupunctural Effects on Hypothalamic-Pituitary-Adrenal Axis During Ethanol Withdrawal.

    Science.gov (United States)

    Zhao, Zheng Lin; Kim, Sang Chan; Zhang, Jie; Liu, Hong Feng; Lee, Bong Hyo; Jang, Eun Young; Lee, Chul Won; Cho, Il Je; An, Won G; Yang, Chae Ha; Kim, Young Woo; Zhao, Rong Jie; Wu, Yi Yan

    2016-02-01

    A previous study demonstrated that acupuncture at ST36 (Zu-San-Li) attenuates ethanol withdrawal (EW)-induced hyperactivation of the hypothalamic-pituitary-adrenal axis in rats. The current study investigated the involvement of hypothalamic norepinephrine (NE) in that process. Rats were intraperitoneally treated with 3 g/kg/d of ethanol or saline for 28 days. After 24 hours of EW, acupuncture was applied to rats at bilateral ST36 points or at nonacupoints (tail) for 1 minute. A high-performance liquid chromatography analysis showed that EW significantly increased both the NE and the 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels in the hypothalamic paraventricular nucleus (PVN). Western blot analysis also revealed that EW markedly elevated the phosphorylation rates of tyrosine hydroxylase (TH), but spared TH protein expression in the PVN. However, acupuncture at ST36, but not at nonacupoints, greatly inhibited the increase in the hypothalamic NE, MHPG, and phosphorylation rates of TH. Additionally, postacupuncture infusion of NE into the PVN significantly attenuated the inhibitory effects of acupuncture at ST36 on the oversecretion of plasma corticosterone during EW. These results suggest that acupuncture at ST36 inhibits EW-induced hyperactivation of the hypothalamic NEergic system to produce therapeutic effects on the hypothalamic-pituitary-adrenal axis.

  9. Influence of ERβ selective agonism during the neonatal period on the sexual differentiation of the rat hypothalamic-pituitary-gonadal (HPG axis

    Directory of Open Access Journals (Sweden)

    Patisaul Heather B

    2012-01-01

    Full Text Available Abstract Background It is well established that sexual differentiation of the rodent hypothalamic-pituitary-gonadal (HPG axis is principally orchestrated by estrogen during the perinatal period. Here we sought to better characterize the mechanistic role the beta form of the estrogen receptor (ERβ plays in this process. Methods To achieve this, we exposed neonatal female rats to three doses (0.5, 1 and 2 mg/kg of the ERβ selective agonist diarylpropionitrile (DPN using estradiol benzoate (EB as a positive control. Measures included day of vaginal opening, estrous cycle quality, GnRH and Fos co-localization following ovariectomy and hormone priming, circulating luteinizing hormone (LH levels and quantification of hypothalamic kisspeptin immunoreactivity. A second set of females was then neonatally exposed to DPN, the ERα agonist propyl-pyrazole-triol (PPT, DPN+PPT, or EB to compare the impact of ERα and ERβ selective agonism on kisspeptin gene expression in pre- and post-pubescent females. Results All three DPN doses significantly advanced the day of vaginal opening and induced premature anestrus. GnRH and Fos co-labeling, a marker of GnRH activation, following ovariectomy and hormone priming was reduced by approximately half at all doses; the magnitude of which was not as large as with EB or what we have previously observed with the ERα agonist PPT. LH levels were also correspondingly lower, compared to control females. No impact of DPN was observed on the density of kisspeptin immunoreactive (-ir fibers or cell bodies in the arcuate (ARC nucleus, and kisspeptin-ir was only significantly reduced by the middle (1 mg/kg DPN dose in the preoptic region. The second experiment revealed that EB, PPT and the combination of DPN+PPT significantly abrogated preoptic Kiss1 expression at both ages but ARC expression was only reduced by EB. Conclusion Our results indicate that selective agonism of ERβ is not sufficient to completely achieve male

  10. Effects of atrazine (ATR), deisopropylatrazine (DIA), Diaminochlorotriazine (DACT) on the hypothalamic-pituitary-adrenal (HPA) axis in female rats

    Science.gov (United States)

    We previously reported that a single dose of the herbicide ATR stimulated the HPA axis in the male rat while equimolar doses of its primary metabolite, DACT, had a minimal effect. In this study, we evaluated the effects of one or four daily doses of ATR, DACT, and an intermediat...

  11. EFFECTS OF ATRAZINE (ATR), DEISOPROPYLATRAZINE (DIA), AND DIAMINOCHLOROTRIAZINE (DACT) ON THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN FEMALE RATS

    Science.gov (United States)

    Previously we reported that a single dose of ATR herbicide stimulated HPA axis activation in the male rat while its primary metabolite, DACT, did so to a lesser extent. In this study, we evaluated the effects of ATR, DACT, and an intermediate metabolite, DIA, on adrenocorticotrop...

  12. Comparative analysis of kisspeptin-immunoreactivity reveals genuine differences in the hypothalamic Kiss1 systems between rats and mice

    DEFF Research Database (Denmark)

    Overgaard, Agnete; Tena-Sempere, Manuel; Franceschini, Isabelle

    2013-01-01

    Kiss1 mRNA and its corresponding peptide products, kisspeptins, are expressed in two restricted brain areas of rodents, the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC). The concentration of mature kisspeptins may not directly correlate with Kiss1 mRNA levels, because...... mRNA translation and/or posttranslational modification, degradation, transportation and release of kisspeptins could be regulated independently of gene expression, and there may thus be differences in kisspeptin expression even in species with similar Kiss1 mRNA profiles. We measured and compared...... kisspeptin-immunoreactivity in both nuclei and both sexes of rats and mice and quantified kisspeptin-immunoreactive nerve fibers. We also determined Kiss1 mRNA levels and measured kisspeptin-immunoreactivity in colchicine pretreated rats. Overall, we find higher levels of kisspeptin...

  13. Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

    OpenAIRE

    Faria, JA; Kinote, A; Ignacio-Souza, LM; de Araujo, TM; Razolli, DS; Doneda, DL; Paschoal, LB; Lellis-Santos, C; Bertolini, GL; Velloso, LA; Bordin, S.; Anhe, GF

    2013-01-01

    Melatonin can contribute to glucose homeostasis either by decreasing gluconeogenesis or by counteracting insulin resistance in distinct models of obesity. However, the precise mechanism through which melatonin controls glucose homeostasis is not completely understood. Male Wistar rats were administered an intracerebroventricular (icv) injection of melatonin and one of following: an icv injection of a phosphatidylinositol 3-kinase (PI3K) inhibitor, an icv injection of a melatonin receptor (MT)...

  14. Glucagon-like peptide 1 (GLP-1) can reverse AMP-activated protein kinase (AMPK) and S6 kinase (P70S6K) activities induced by fluctuations in glucose levels in hypothalamic areas involved in feeding behaviour.

    Science.gov (United States)

    Hurtado-Carneiro, Verónica; Sanz, Carmen; Roncero, Isabel; Vazquez, Patricia; Blazquez, Enrique; Alvarez, Elvira

    2012-04-01

    The anorexigenic peptide, glucagon-like peptide-1 (GLP-1), reduces glucose metabolism in the human hypothalamus and brain stem. The brain activity of metabolic sensors such as AMP-activated protein kinase (AMPK) responds to changes in glucose levels. The mammalian target of rapamycin (mTOR) and its downstream target, p70S6 kinase (p70S6K), integrate nutrient and hormonal signals. The hypothalamic mTOR/p70S6K pathway has been implicated in the control of feeding and the regulation of energy balances. Therefore, we investigated the coordinated effects of glucose and GLP-1 on the expression and activity of AMPK and p70S6K in the areas involved in the control of feeding. The effect of GLP-1 on the expression and activities of AMPK and p70S6K was studied in hypothalamic slice explants exposed to low- and high-glucose concentrations by quantitative real-time RT-PCR and by the quantification of active-phosphorylated protein levels by immunoblot. In vivo, the effects of exendin-4 on hypothalamic AMPK and p70S6K activation were analysed in male obese Zucker and lean controls 1 h after exendin-4 injection to rats fasted for 48 h or after re-feeding for 2-4 h. High-glucose levels decreased the expression of Ampk in the lateral hypothalamus and treatment with GLP-1 reversed this effect. GLP-1 treatment inhibited the activities of AMPK and p70S6K when the activation of these protein kinases was maximum in both the ventromedial and lateral hypothalamic areas. Furthermore, in vivo s.c. administration of exendin-4 modulated AMPK and p70S6K activities in those areas, in both fasted and re-fed obese Zucker and lean control rats.

  15. The effect of 8 weeks of endurance training on hypothalamic Nesfatin-1 gene expression and its concentration in male rats

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    Abbas Ghanbari Niaki

    2012-09-01

    Full Text Available Background: Hypothalamus is mentioned as the major center of appetite and energy balance. Physical activity and the exersice are able to disturb the energy balance to negative. Nesfatin-1 is a regulating neuropeptide that is produced by hypothalamus and has an important role in establishing energy balance. The purpose of this study was to examine the effect of endurance training regimen on nesfatin-1 gene expression and its concentration in the male rat hypothalamus. Materials and Methods: Eleven adult wistar male rats (8-10 week old, 130-145g assigned into control(C, n=5 and training (E, n=6 groups. Training group was given exercise on a motor-driven treadmill (20m/min, 0% grade, 60 min/session, 5days/week for 8 weeks. Rats were sacrificed 72h after the last training session and then the hypothalamus tissue was excised for determination of nesfatin-1 gene expression and its concentration by RT-PCR & ELIZA methods, respectively. Four hours before the experiment the food not tap water was removed from the animal cages. Data was analyzed by using an independent t-student test. Results: The current results indicated that the levels of nesfatin-1 gene expression and its concentration, ATP, and glycogen concentrations were non-significantly lower in trained group when compared with control group. Conclusion: This research showed for the first time, that a low-intensity exercises, decreases nesfatin-1 expression and concentration in the hypothalamus, which accompanied insignificant reduction in energy source. It seems that in the present research, the exercise has had the same fasting and being hungry like effect on nesfatin-1 expression and concentration in the hypothalamus.

  16. Elevated blood lactate is not a primary cause of anorexia in tumor-bearing rats.

    Science.gov (United States)

    Chance, William T; Dayal, Ramesh; Friend, Lou Ann; James, J Howard

    2004-01-01

    Tumor-bearing (TB) rats exhibit elevated concentrations of lactate in blood contiguous with the development of anorexia. Continuous intravenous infusion of lactate into non-TB rats reduced food intake at plasma concentrations lower than those observed in anorectic TB rats. Levels of neuropeptide Y (NPY) were elevated in the ventromedial (VMH) and dorsomedial hypothalamic regions of lactate-infused rats. The addition of the enhancer of pyruvate dehydrogenase activity, dichloroacetate (DCA), to the drinking water of TB rats (0.1-0.4%) normalized blood lactate concentration but had no significant effect on anorexia. However, the elevated concentration of NPY in the VMH of anorectic TB rats was also normalized by the DCA treatment. No alterations in regional hypothalamic levels of corticotropin-releasing factor were observed within any treatment conditions. These results suggest that, although hyperlactatemia may be involved in maintaining elevated NPY concentrations in anorectic TB rats, it does not appear to be a significant factor in the etiology of experimental cancer anorexia.

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

    Science.gov (United States)

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

    2015-04-10

    The hypothalamus regulates a number of autonomic functions essential for homeostasis; therefore, investigations concerning hypothalamic neuropeptides and their functions and distribution are of great importance in contemporary neuroscience. Recently, novel regulatory factors expressed in the hypothalamus have been discovered, of which nesfatin-1 and phoenixin (PNX), show intriguing similarities in their brain distributions. There are currently few studies characterizing PNX expression, so it is imperative to accurately trace its localization, with particular attention to the hypothalamic nuclei and nesfatin-1 co-expression. Using fluorescence and classical immunohistochemical stainings on adult rat brain, we visualized the potential co-expression of nesfatin-1 and PNX immunoreactive cells. We have demonstrated a distinct PNX-immunoreactivity in 21-32% of cells in the arcuate nucleus, paraventricular nucleus, ventromedial and lateral hypothalamus. Nesfatin-1 expression reached 45-68% of all neurons in the same sites, while co-expression was strikingly seen in the vast majority (70-86%) of PNX-immunoreactive neurons in the rat hypothalamic nuclei. Our results demonstrate for the first time, a wide distribution of PNX in the hypothalamus which could implicate a potential functional relationship with nesfatin-1, possibly in the regulation of the hypothalamic-pituitary-gonadal axis or other autonomic functions, which require further study. Copyright © 2015. Published by Elsevier Ireland Ltd.

  18. Short-term regulation of the hypothalamic melanocortinergic system under fasting and defined glucose-refeeding conditions in rats: a laser capture microdissection (LMD)-based study.

    Science.gov (United States)

    Landmann, Emelie M; Schellong, Karen; Melchior, Kerstin; Rodekamp, Elke; Ziska, Thomas; Harder, Thomas; Plagemann, Andreas

    2012-04-25

    It is well established that under fasting conditions the expression of the orexigenic neuropeptide agouti-related peptide (AGRP) is up-regulated in the hypothalamic arcuate nucleus (ARC), while inconsistent data exist regarding fasting regulation of the anorexigenic neurohormone proopiomelanocortin (POMC). Inconsistencies might have methodological reasons, especially concerning neuromorphological and/or experimental (nutritional) specificity. We analyzed the expression of both neuropeptides in ARC neurons, using lasercapture microdissection (LMD) and real-time PCR in 12h fasted vs. fed Wistar rats as well as after a standardized glucose load, i.e., under clinically relevant conditions in terms of diagnosing glucose intolerance in the human. Under fasting conditions, clear up-regulation of AGRP was observed, with increasing magnitude in ARC single neurons (SNP) as compared to ARC cell layers (+125% vs. +23%, resp.), closely correlated to hypoinsulinemia and hypoleptinemia. Surprisingly, in the fasting state POMC was not found to be down-regulated, neither in ARC cell layers nor in ARC single neurons (+9% vs. +6%). However, glucose-refeeding under diagnostically relevant conditions led to strong neuronal up-regulation of POMC expression in ARC SNP (+128%), and AGRP down-regulation (-50%). In conclusion, experimentally, topographically, and analytically specific and standardized conditions confirmed AGRP in ARC neurons as being neuronally up- and down-regulated, resp., depending on the general nutritional state, while POMC was found to be (up-) regulated only after peripheral glucose load. Findings suggest that POMC in ARC neurons acts glucose-mediated as an "anti-orexigenic" neurohormone, specifically responding to hyperglycemia.

  19. Retrograde study of CART- or NPY-neuronal projection from the hypothalamic arcuate nucleus to the dorsal raphe and/or the locus coeruleus in the rat.

    Science.gov (United States)

    Yoon, Ye S; Lee, Ji S; Lee, Hyun S

    2013-06-26

    The present study was designed to reveal cocaine- and amphetamine-regulated transcript (CART)- or neuropeptide Y (NPY)-immunoreactive neuronal projections from the hypothalamic arcuate nucleus (Arc) to the dorsal raphe (DR) and/or the locus coeruleus (LC) in the rat. Our results demonstrated that CART or NPY axon terminals formed close appositions to the neuronal profiles in the DR and the LC. Thus, arcuate sections were immunostained for the CART or NPY after the injections of green RetroBeads(™) into the DR and red tracer into the LC (or vice versa). First, retrogradely-labeled CART cells were mainly observed in the lateral Arc without colchicine. Of the total population of arcuate CART neurons, DR- and LC-projecting cells were 5.7% ± 0.9% and 6.6% ± 0.7%, respectively. In addition, a subset (3.3% ± 0.7%) of CART neurons provided divergent axon collaterals to the DR and the LC. Second, retrogradely-labeled NPY cells were observed in lateral or ventral borders of the medial Arc only after colchicine injection. Of the entire NPY cell population, DR- and LC-projecting neurons were 1.5% ± 0.3% and 1.3% ± 0.3%, respectively. Only a scanty proportion (0.1% ± 0.0%) sent axon collaterals to the DR and the LC. These observations suggested that arcuate CART or NPY system might have a potential influence on the brainstem monoaminergic nuclei, modulating their roles in feeding, nociception, emotional behaviors, arousal, and stress responses. Furthermore, a portion of arcuate CART neurons (along with only a few NPY cells) sending divergent axon collaterals to the DR/LC might have a simultaneous (and possibly more efficient) way to exert their specific influences on the monoaminergic nuclei.

  20. Citrus aurantium and Rhodiola rosea in combination reduce visceral white adipose tissue and increase hypothalamic norepinephrine in a rat model of diet-induced obesity

    Science.gov (United States)

    Verpeut, Jessica L.; Walters, Amy L.; Bello, Nicholas T.

    2013-01-01

    Extracts from the immature fruit of Citrus aurantium are often used for weight loss but are reported to produce adverse cardiovascular effects. Root extracts of Rhodiola rosea have notable antistress properties. The hypothesis of these studies was that C aurantium (6% synephrine) and R rosea (3% rosavins, 1% salidroside) in combination would improve diet-induced obesity alterations in adult male Sprague-Dawley rats. In normal-weight animals fed standard chow, acute administration of C aurantium (1-10 mg/kg) or R rosea (2-20 mg/kg) alone did not reduce deprivation-induced food intake, but C aurantium (5.6 mg/kg) + R rosea (20 mg/kg) produced a 10.5% feeding suppression. Animals maintained (13 weeks) on a high-fat diet (60% fat) were exposed to 10-day treatments of C aurantium (5.6 mg/kg) or R rosea (20 mg/kg) alone or in combination. Additional groups received vehicle (2% ethanol) or were pair fed to the C aurantium + R rosea group. Although high-fat diet intake and weight loss were not influenced, C aurantium + R rosea had a 30% decrease in visceral fat weight compared with the other treatments. Only the C aurantium group had an increased heart rate (+7%) compared with vehicle. In addition, C aurantium + R rosea administration resulted in an elevation (+15%) in hypothalamic norepinephrine and an elevation (+150%) in frontal cortex dopamine compared with the pair-fed group. These initial findings suggest that treatments of C aurantium + R rosea have actions on central monoamine pathways and have the potential to be beneficial for the treatment of obesity. PMID:23746567

  1. High-fructose diet leads to visceral adiposity and hypothalamic leptin resistance in male rats--do glucocorticoids play a role?

    Science.gov (United States)

    Bursać, Biljana N; Vasiljević, Ana D; Nestorović, Nataša M; Veličković, Nataša A; Vojnović Milutinović, Danijela D; Matić, Gordana M; Djordjevic, Ana D

    2014-04-01

    Fructose overconsumption has been involved in the genesis and progression of the metabolic syndrome. Hypothalamus and adipose tissue, major organs for control of food intake and energy metabolism, play crucial roles in metabolic homeostasis. We hypothesized that glucocorticoid signaling mediates the effects of a fructose-enriched diet on visceral adiposity by acting on neuropeptide Y (NPY) in the hypothalamus and altering adipogenic transcription factors in the visceral adipose tissue. We analyzed the effects of 9-week consumption of 60% fructose solution on dyslipidemia, insulin and leptin sensitivity, and adipose tissue histology in male Wistar rats. Glucocorticoid signaling was assessed in both hypothalamus and visceral adipose tissue, while the levels of peroxisome-proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein-1 (SREBP-1) and lipin-1, together with the levels of their target genes expression, were analyzed in the visceral adipose tissue. The results showed that long-term consumption of highly concentrated liquid fructose led to the development of visceral adiposity, elevated triglycerides and hypothalamic leptin resistance accompanied by stimulated glucocorticoid signaling and NPY mRNA elevation. Results from adipose tissue implied that fructose consumption shifted the balance between glucocorticoid receptor and adipogenic transcriptional factors (PPARγ, SREBP-1 and lipin-1) in favor of adipogenesis judged by distinctly separated populations of small adipocytes observed in this tissue. In summary, we propose that high-fructose-diet-induced alterations of glucocorticoid signaling in both hypothalamus and adipose tissue result in enhanced adipogenesis, possibly serving as an adaptation to energy excess in order to limit deposition of fat in nonadipose tissues. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Lateral hypothalamic area orexin-A influence the firing activity of gastric distension-sensitive neurons and gastric motility in rats.

    Science.gov (United States)

    Hao, Heling; Luan, Xiao; Guo, Feifei; Sun, Xiangrong; Gong, Yanling; Xu, Luo

    2016-06-01

    The orexins system consists of two G-protein coupled receptors (the orexin-1 and the orexin-2 receptor) and two neuropeptides, orexin-A and orexin-B. Orexin-A is an excitatory neuropeptide that regulates arousal, wakefulness and appetite. Recent studies have shown that orexin-A may promote gastric motility. We aim to explore the effects of orexin-A on the gastric -distension (GD) sensitive neurons and gastric motility in the lateral hypothalamic area (LHA), and the possible regulation by the paraventricular nucleus (PVN). Extracellular single unit discharges were recorded and the gastric motility was monitored by administration of orexin-A into the LHA and electrical stimulation of the PVN. There were GD neurons in the LHA, and administration of orexin-A to the LHA could increase the firing rate of both GD-excitatory (GD-E) and GD-inhibited (GD-I) neurons. The gastric motility was significantly enhanced by injection of orexin-A into the LHA with a dose dependent manner, which could be completely abolished by pre-treatment with orexin-A receptor antagonist SB334867. Electrical stimulation of the PVN could significantly increase the firing rate of GD neurons responsive to orexin-A in the LHA as well as promote gastric motility of rats. However, those effects could be partly blocked by pre-treatment with SB334867 in the LHA. It is suggested that orexin-A plays an important role in promoting gastric motility via LHA. The PVN may be involved in regulation of LHA on gastric motility.

  3. Effect of hypoxia on hypothalamic cannabinoid receptor type Ⅰ expression and food intake in rats%缺氧对大鼠下丘脑Ⅰ型大麻素受体表达和摄食量的影响

    Institute of Scientific and Technical Information of China (English)

    汪冬; 杨帆; 黄庆愿; 周其全

    2016-01-01

    目的 研究缺氧大鼠下丘脑Ⅰ型大麻素受体(cannabinoid receptor type Ⅰ,CB1)的表达变化及其与摄食量的关系.方法 54只雄性SD大鼠按随机数字表法分为3组(每组18只):平原对照组、缺氧1d组和缺氧7d组.缺氧组大鼠置模拟海拔5000m低压舱中,平原对照组大鼠置平原饲养.记录各组大鼠摄食量,蛋白免疫印迹法和免疫组化法观察各组大鼠下丘脑CB1受体和c-Fos蛋白表达变化.结果 与平原对照组[(15.5±2.7)g]大鼠相比,缺氧1d组大鼠摄食量[(4.9±0.7)g]显著减少(P<0.05),同时大鼠下丘脑CB1和c-Fos阳性细胞数量和蛋白表达量显著减少;缺氧1d组大鼠弓状核(arcuate nucleus,ARC)、下丘脑腹外侧区(later hypothalamic area,LH)和下丘脑腹内侧核(ventromedial hypothalamic nucleus,VMH)CB1受体、c-Fos表达较平原对照组显著降低;随着缺氧时间的延长,动物摄食量逐日增加,缺氧3~7d时的摄食量与平原对照组大鼠相当;缺氧7d组大鼠下丘脑CB1受体和c-Fos阳性细胞数量和蛋白表达量与平原对照组大鼠比较,差异无统计学意义(P>0.05).结论 急性缺氧大鼠摄食减少可能与弓状核、下丘脑腹外侧区和下丘脑腹内侧核CB1受体和c-Fos表达减少相关.

  4. Effects of fluoxetine administration on regional galanin expression in obese Zucker rat hypothalamus.

    Science.gov (United States)

    Churruca, Itziar; Portillo, María P; Gutiérreza, Arantza; Casis, Luis; Macarulla, María Teresa; Zarate, Jon; Echevarría, Enrique

    2004-06-01

    The aim of the present work was to study the potential involvement of hypothalamic galanin system in the anorectic mechanism of fluoxetine in obese Zucker rats. Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg; i.p.) daily for two weeks. The control group was given 0.9% NaCl solution. Significant decreases in food intake, final body weight and total body fat were observed after fluoxetine treatment. Although fluoxetine-treated rats showed a decrease in urine elimination, this effect was not enough to compensate decreased water intake, leading to dehydration, as showed by decreased body water content. Chronic fluoxetine administration increased the numbers of galanin positively immunostained neural cells in medial and lateral preoptic areas, lateral hypothalamic area and paraventricular nucleus (rostral and magnocellular regions), without changes in dorsomedial, ventromedial, supraoptic, suprachiasmatic and arcuate nuclei. Taken into account that galanin stimulates appetite, these results could represent rather a compensatory response against reduced food intake than a direct anorectic mechanism. Changes in the magnocellular region of the hypothalamic paraventricular nucleus suggest a role for galanin neural circuits at this level in fluoxetine-induced hydro-osmotic impairment.

  5. Effects of food deprivation on the hypothalamic feeding-regulating peptides gene expressions in serotonin depleted rats.

    Science.gov (United States)

    Yoshimura, Mitsuhiro; Hagimoto, Marina; Matsuura, Takanori; Ohkubo, Junichi; Ohno, Motoko; Maruyama, Takashi; Ishikura, Toru; Hashimoto, Hirofumi; Kakuma, Tetsuya; Yoshimatsu, Hironobu; Terawaki, Kiyoshi; Uezono, Yasuhito; Toyohira, Yumiko; Yanagihara, Nobuyuki; Ueta, Yoichi

    2014-03-01

    We examined the effects of serotonin (5-HT) depletion induced by peripheral injection of 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) on the expression of feeding-regulating peptides expressions by using in situ hybridization histochemistry in adult male Wistar rats. PCPA pretreatment had no significant effect on basal levels of oxytocin, corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), pro-opiomelanocortin (POMC), cocaine and amphetamine-regulated transcript (CART), neuropeptide-Y (NPY), agouti-related protein (AgRP), melanin-concentrating hormone (MCH) or orexin in the hypothalamus. Food deprivation for 48 h caused a significant decrease in CRH, TRH, POMC, and CART, and a significant increase in NPY, AgRP and MCH. After PCPA treatment, POMC and CART did not decrease despite food deprivation. NPY was significantly increased by food deprivation with PCPA, but was attenuated compared to food deprivation without PCPA. These results suggest that the serotonergic system in the hypothalamus may be involved in the gene expression of POMC, CART, and NPY related to feeding behavior.

  6. Chronic administration of the metastin/kisspeptin analog KISS1-305 or the investigational agent TAK-448 suppresses hypothalamic pituitary gonadal function and depletes plasma testosterone in adult male rats.

    Science.gov (United States)

    Matsui, Hisanori; Tanaka, Akira; Yokoyama, Kotaro; Takatsu, Yoshihiro; Ishikawa, Kaori; Asami, Taiji; Nishizawa, Naoki; Suzuki, Atsuko; Kumano, Satoshi; Terada, Michiko; Kusaka, Masami; Kitada, Chieko; Ohtaki, Tetsuya

    2012-11-01

    Metastin/kisspeptin, a hypothalamic peptide, plays a pivotal role in controlling GnRH neurons. Here we studied the effect of chronic sc administration of two kisspeptin analogs, KISS1-305 and TAK-448, on hypothalamic-pituitary-gonadal function in male rats in comparison with a GnRH analogue leuprolide or bilateral orchiectomy (ORX). The prototype polypeptide, KISS1-305 (1-4 nmol/h), caused substantial elevations of plasma LH and testosterone, followed by abrupt reductions of both hormone levels. Notably, testosterone levels were reduced to castrate levels within 3 d and remained depleted throughout the 4-wk dosing period, an effect that was faster and more pronounced than leuprolide (1 nmol/h) dosing. KISS1-305 also reduced genital organ weight more profoundly than leuprolide. In mechanistic studies, chronic KISS1-305 administration only transiently induced c-Fos expression in GnRH neurons, suggesting that GnRH-neural response was attenuated over time. Hypothalamic GnRH content was reduced to 10-20% of control at 3 wk without any changes in Gnrh mRNA expression. Dosing with the investigational peptide TAK-448 was also studied to extend our understanding of hypothalamic-pituitary functions. Similar to ORX, TAK-448 (0.1 nmol/h) depleted testosterone and decreased GnRH content by 4 wk. However, in contrast to ORX, TAK-448 decreased gonadotropin levels in pituitary and plasma samples, implying the suppression of GnRH pulses. These results suggest that chronic administration of kisspeptin analogs disrupts endogenous kisspeptin signals to suppress intrinsic GnRH pulses, perhaps by attenuating GnRH-neural response and inducing continuous GnRH leakage from the hypothalamus. The potential utility of kisspeptin analogs as novel agents to treat hormone-related diseases, including prostate cancer, is discussed.

  7. 5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

    Directory of Open Access Journals (Sweden)

    Malgorzata S. Martin-Gronert

    2016-04-01

    Full Text Available Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC peptides within the arcuate nucleus of the hypothalamus (ARC. We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus of in utero growth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist.

  8. 5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

    Science.gov (United States)

    Martin-Gronert, Malgorzata S.; Stocker, Claire J.; Wargent, Edward T.; Cripps, Roselle L.; Garfield, Alastair S.; Jovanovic, Zorica; D'Agostino, Giuseppe; Yeo, Giles S. H.; Cawthorne, Michael A.; Arch, Jonathan R. S.; Heisler, Lora K.; Ozanne, Susan E.

    2016-01-01

    ABSTRACT Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus of in utero growth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist. PMID:26769798

  9. Differential Involvement of Dopamine D1 Receptor and MEK Signaling Pathway in the Ventromedial Prefrontal Cortex in Consolidation and Reconsolidation of Recognition Memory

    Science.gov (United States)

    Maroun, Mouna; Akirav, Irit

    2009-01-01

    We investigated MEK and D1 receptors in the ventromedial prefrontal cortex (vmPFC) in consolidation and reconsolidation of recognition memory in rats nonhabituated to the experimental context (NH) or with reduced arousal due to extensive prior habituation (H). The D1 receptor antagonist enhanced consolidation and impaired reconsolidation in NH but…

  10. Upregulation of CB₁ receptor binding in the ventromedial prefrontal cortex promotes proactive stress-coping strategies following chronic stress exposure.

    Science.gov (United States)

    McLaughlin, R J; Hill, M N; Dang, S S; Wainwright, S R; Galea, L A M; Hillard, C J; Gorzalka, B B

    2013-01-15

    Accumulating evidence has revealed that dysregulation of the endocannabinoid system could contribute to the development of major depression. Studies carried out post-mortem in depressed suicide victims have revealed increased CB(1) receptor binding site density in the prefrontal cortex (PFC). Accordingly, exposure of rodents to chronic unpredictable stress (CUS) results in phenotypic changes that mirror those of human depression, including increased CB(1) receptor binding site density in the PFC. Our goal in these studies was to examine the effects of CUS on the density of CB(1) receptor binding sites in the rodent medial PFC and to explore the role of this alteration in the behavioral changes invoked by CUS. Rodents exposed to CUS exhibited increased CB(1) receptor maximal binding site density (B(max)) within the ventromedial PFC, but not the dorsomedial PFC. To determine whether this change in the ventromedial PFC is an adaptive response, or alternatively, a consequence of chronic stress that contributes to the adoption of passive coping, we examined whether local CB(1) receptor blockade within the ventromedial PFC following CUS would significantly alter behaviors in the forced swim test (FST). CUS exposure significantly increased passive coping in the FST, and this was further augmented by discrete ventromedial PFC microinfusions of the CB(1) receptor antagonist AM251 prior to swim stress. Moreover, local CB(1) receptor blockade reduced active coping responses in CUS-exposed rats. These findings suggest that the increase in CB(1) receptor B(max) observed in the ventromedial PFC of rodents exposed to CUS maintains proactive coping strategies following chronic stress exposure.

  11. The alpha(2)-adrenoceptors do not modify the activity of tyrosine hydroxylase, corticoliberine, and neuropeptide Y producing hypothalamic magnocellular neurons ion the Long Evans and Brattleboro rats

    DEFF Research Database (Denmark)

    Bundzikova, J; Pirnik, Z; Zelena, D

    2010-01-01

    The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei are activated by body salt-fluid variations. Stimulation of alpha(2)-adrenoceptors by an agonist-xylazine (XYL) activates oxytocinergic but not vasopressinergic magnocellular neurons. In this study, tyrosine hydroxylase (TH), cort...

  12. Glucose Sensing Neurons in the Ventromedial Hypothalamus

    Directory of Open Access Journals (Sweden)

    Vanessa H. Routh

    2010-10-01

    Full Text Available Neurons whose activity is regulated by glucose are found in a number of brain regions. Glucose-excited (GE neurons increase while glucose-inhibited (GI neurons decrease their action potential frequency as interstitial brain glucose levels increase. We hypothesize that these neurons evolved to sense and respond to severe energy deficit (e.g., fasting that threatens the brains glucose supply. During modern times, they are also important for the restoration of blood glucose levels following insulin-induced hypoglycemia. Our data suggest that impaired glucose sensing by hypothalamic glucose sensing neurons may contribute to the syndrome known as hypoglycemia-associated autonomic failure in which the mechanisms which restore euglycemia following hypoglycemia become impaired. On the other hand, increased responses of glucose sensing neurons to glucose deficit may play a role in the development of Type 2 Diabetes Mellitus and obesity. This review will discuss the mechanisms by which glucose sensing neurons sense changes in interstitial glucose and explore the roles of these specialized glucose sensors in glucose and energy homeostasis.

  13. Dynamic imaging of free cytosolic ATP concentration during fuel sensing by rat hypothalamic neurones: evidence for ATP-independent control of ATP-sensitive K(+) channels.

    Science.gov (United States)

    Ainscow, Edward K; Mirshamsi, Shirin; Tang, Teresa; Ashford, Michael L J; Rutter, Guy A

    2002-10-15

    Glucose-responsive (GR) neurons from hypothalamic nuclei are implicated in the regulation of feeding and satiety. To determine the role of intracellular ATP in the closure of ATP-sensitive K(+) (K(ATP)) channels in these cells and associated glia, the cytosolic ATP concentration ([ATP](c)) was monitored in vivo using adenoviral-driven expression of recombinant targeted luciferases and bioluminescence imaging. Arguing against a role for ATP in the closure of K(ATP) channels in GR neurons, glucose (3 or 15 mM) caused no detectable increase in [ATP](c), monitored with cytosolic luciferase, and only a small decrease in the concentration of ATP immediately beneath the plasma membrane, monitored with a SNAP25-luciferase fusion protein. In contrast to hypothalamic neurons, hypothalamic glia responded to glucose (3 and 15 mM) with a significant increase in [ATP](c). Both neurons and glia from the cerebellum, a glucose-unresponsive region of the brain, responded robustly to 3 or 15 mM glucose with increases in [ATP](c). Further implicating an ATP-independent mechanism of K(ATP) channel closure in hypothalamic neurons, removal of extracellular glucose (10 mM) suppressed the electrical activity of GR neurons in the presence of a fixed, high concentration (3 mM) of intracellular ATP. Neurons from both brain regions responded to 5 mM lactate (but not pyruvate) with an oligomycin-sensitive increase in [ATP](c). High levels of the plasma membrane lactate-monocarboxylate transporter, MCT1, were found in both cell types, and exogenous lactate efficiently closed K(ATP) channels in GR neurons. These data suggest that (1) ATP-independent intracellular signalling mechanisms lead to the stimulation of hypothalamic neurons by glucose, and (2) these effects may be potentiated in vivo by the release of lactate from neighbouring glial cells.

  14. Dynamic imaging of free cytosolic ATP concentration during fuel sensing by rat hypothalamic neurones: evidence for ATP-independent control of ATP-sensitive K+ channels

    Science.gov (United States)

    Ainscow, Edward K; Mirshamsi, Shirin; Tang, Teresa; Ashford, Michael L J; Rutter, Guy A

    2002-01-01

    Glucose-responsive (GR) neurons from hypothalamic nuclei are implicated in the regulation of feeding and satiety. To determine the role of intracellular ATP in the closure of ATP-sensitive K+ (KATP) channels in these cells and associated glia, the cytosolic ATP concentration ([ATP]c) was monitored in vivo using adenoviral-driven expression of recombinant targeted luciferases and bioluminescence imaging. Arguing against a role for ATP in the closure of KATP channels in GR neurons, glucose (3 or 15 mm) caused no detectable increase in [ATP]c, monitored with cytosolic luciferase, and only a small decrease in the concentration of ATP immediately beneath the plasma membrane, monitored with a SNAP25–luciferase fusion protein. In contrast to hypothalamic neurons, hypothalamic glia responded to glucose (3 and 15 mm) with a significant increase in [ATP]c. Both neurons and glia from the cerebellum, a glucose-unresponsive region of the brain, responded robustly to 3 or 15 mm glucose with increases in [ATP]c. Further implicating an ATP-independent mechanism of KATP channel closure in hypothalamic neurons, removal of extracellular glucose (10 mm) suppressed the electrical activity of GR neurons in the presence of a fixed, high concentration (3 mm) of intracellular ATP. Neurons from both brain regions responded to 5 mm lactate (but not pyruvate) with an oligomycin-sensitive increase in [ATP]c. High levels of the plasma membrane lactate-monocarboxylate transporter, MCT1, were found in both cell types, and exogenous lactate efficiently closed KATP channels in GR neurons. These data suggest that (1) ATP-independent intracellular signalling mechanisms lead to the stimulation of hypothalamic neurons by glucose, and (2) these effects may be potentiated in vivo by the release of lactate from neighbouring glial cells. PMID:12381816

  15. CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin

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    Pierre Cardinal

    2014-10-01

    Full Text Available Metabolic flexibility allows rapid adaptation to dietary change, however, little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoid type-1 (CB1 receptors are expressed in VMN neurons, but the specific contribution of endocannabinoid signaling in this neuronal population to energy balance regulation is unknown. Here we demonstrate that VMN CB1 receptors regulate metabolic flexibility and actions of leptin. In chow-fed mice, conditional deletion of CB1 in VMN neurons (expressing the steroidogenic factor 1, SF1 decreases adiposity by increasing sympathetic activity and lipolysis, and facilitates metabolic effects of leptin. Conversely, under high-fat diet, lack of CB1 in VMN neurons produces leptin resistance, blunts peripheral use of lipid substrates and increases adiposity. Thus, CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change.

  16. CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin.

    Science.gov (United States)

    Cardinal, Pierre; André, Caroline; Quarta, Carmelo; Bellocchio, Luigi; Clark, Samantha; Elie, Melissa; Leste-Lasserre, Thierry; Maitre, Marlene; Gonzales, Delphine; Cannich, Astrid; Pagotto, Uberto; Marsicano, Giovanni; Cota, Daniela

    2014-10-01

    Metabolic flexibility allows rapid adaptation to dietary change, however, little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN) participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoid type-1 (CB1) receptors are expressed in VMN neurons, but the specific contribution of endocannabinoid signaling in this neuronal population to energy balance regulation is unknown. Here we demonstrate that VMN CB1 receptors regulate metabolic flexibility and actions of leptin. In chow-fed mice, conditional deletion of CB1 in VMN neurons (expressing the steroidogenic factor 1, SF1) decreases adiposity by increasing sympathetic activity and lipolysis, and facilitates metabolic effects of leptin. Conversely, under high-fat diet, lack of CB1 in VMN neurons produces leptin resistance, blunts peripheral use of lipid substrates and increases adiposity. Thus, CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change.

  17. Role of leptin in energy expenditure: the hypothalamic perspective.

    Science.gov (United States)

    Pandit, R; Beerens, S; Adan, R A H

    2017-06-01

    The adipocyte-derived hormone leptin is a peripheral signal that informs the brain about the metabolic status of an organism. Although traditionally viewed as an appetite-suppressing hormone, studies in the past decade have highlighted the role of leptin in energy expenditure. Leptin has been shown to increase energy expenditure in particular through its effects on the cardiovascular system and brown adipose tissue (BAT) thermogenesis via the hypothalamus. The current review summarizes the role of leptin signaling in various hypothalamic nuclei and its effects on the sympathetic nervous system to influence blood pressure, heart rate, and BAT thermogenesis. Specifically, the role of leptin signaling on three different hypothalamic nuclei, the dorsomedial hypothalamus, the ventromedial hypothalamus, and the arcuate nucleus, is reviewed. It is known that all of these brain regions influence the sympathetic nervous system activity and thereby regulate BAT thermogenesis and the cardiovascular system. Thus the current work focuses on how leptin signaling in specific neuronal populations within these hypothalamic nuclei influences certain aspects of energy expenditure. Copyright © 2017 the American Physiological Society.

  18. Separate populations of neurons within the paraventricular hypothalamic nucleus of the rat project to vagal and thoracic autonomic preganglionic levels and express c-Fos protein induced by lithium chloride.

    Science.gov (United States)

    Portillo, F; Carrasco, M; Vallo, J J

    1998-03-01

    The role of different hypothalamic nuclei, particularly the paraventricular nucleus (PVN), in the control of food intake and feeding behaviour is well known. It is also well established that lithium chloride (LiCl) causes various disorders in feeding behaviour. In this study, we analyzed the precise distribution of hypothalamic neurons activated by i.p. LiCl administration (LCA neurons) and compared it to that of hypothalamic neurons which project to autonomic preganglionic levels (HAP neurons). We also analysed the possibility that some neurons belong to both populations of nerve cells. To this end, a multiple-labelling technique, using two retrograde fluorescent tracers together with c-Fos-like immunohistochemistry, was performed. Fast Blue was injected in the dorsal motor nucleus of the vagus and Fluorogold (FG) in the thoracic intermedial-lateral cell column, to trace parasympathetic and sympathetic pathways, respectively. LiCl was used as stimulus for c-Fos-like immunohistochemistry. HAP neurons were located mainly in the dorsal, ventral and lateral regions of the parvocellular PVN, while LCA neurons were observed predominantly in the magnocellular region of the PVN rostrally to HAP neurons. A significant number of FG/Fos double-labelled neurons were located in the dorsal parvocellular subnucleus of the PVN (dp) in the LiCl-stimulated rats. We concluded that there is a clear segregation of LCA neurons from HAP neurons within the PVN. The presence of FG/Fos double-labelled neurons in the dp suggests that this nucleus could mediate a sympathetic response after LiCl administration.

  19. Exposure to a highly caloric palatable diet during pregestational and gestational periods affects hypothalamic and hippocampal endocannabinoid levels at birth and induces adiposity and anxiety-like behaviors in male rat offspring

    Directory of Open Access Journals (Sweden)

    Maria Teresa eRamírez-López

    2016-01-01

    Full Text Available Exposure to unbalanced diets during pre-gestational and gestational periods may result in long-term alterations in metabolism and behavior. The contribution of the endocannabinoid system to these long-term adaptive responses is unknown. In the present study, we investigated the impact of female rat exposure to a hypercaloric-hypoproteic palatable diet during pre-gestational, gestational and lactational periods on the development of male offspring. In addition, the hypothalamic and hippocampal endocannabinoid contents at birth and the behavioral performance in adulthood were investigated. Exposure to a palatable diet resulted in low weight offspring who exhibited low hypothalamic contents of arachidonic acid and the two major endocannabinoids (anandamide and 2-arachidonoylglycerol at birth. Palmitoylethanolamide, but not oleoylethanolamide, also decreased. Additionally, pups from palatable diet-fed dams displayed lower levels of anandamide and palmitoylethanolamide in the hippocampus. The low-weight male offspring, born from palatable diet exposed mothers, gained less weight during lactation and, although they recovered weight during the post-weaning period, they developed abdominal adiposity in adulthood. These animals exhibited anxiety-like behavior in the elevated plus-maze and open field test and a low preference for a chocolate diet in a food preference test, indicating that maternal exposure to a hypercaloric diet induces long-term behavioral alterations in male offspring. These results suggest that maternal diet alterations in the function of the endogenous cannabinoid system can mediate the observed phenotype of the offspring, since both hypothalamic and hippocampal endocannabinoids regulate feeding, metabolic adaptions to caloric diets, learning, memory and emotions.

  20. Differential effects of central and peripheral administration of growth hormone (GH) and insulin-like growth factor on hypothalamic GH-releasing hormone and somatostatin gene expression in GH-deficient dwarf rats.

    Science.gov (United States)

    Sato, M; Frohman, L A

    1993-08-01

    The roles of GH and insulin-like growth factor-I (IGF-I) in the regulation of hypothalamic GH-releasing hormone (GRH) and somatostatin (SRIH) gene expression were investigated in the GH-deficient dwarf (dw) rat, in which endogenous feedback signals are lacking. Adult male and female dw rats were treated with GH or IGF-I by systemic (sc) administration or intracerebroventricular (icv) infusion, and hypothalamic GRH and SRIH mRNA were determined by Northern blotting and densitometric analysis. Systemic sc injection of rGH (75 micrograms every 12 h for 3 days) decreased GRH mRNA levels in both sexes. However, systemic sc injection of human IGF-I (150 micrograms every 12 h for 3 days) did not affect GRH mRNA levels in either sex despite significant stimulation of body weight gain. The use of a continuous sc infusion, which normalized serum IGF-I levels, and prolongation of the treatment period to 7 days also failed to change GRH mRNA levels. SRIH mRNA was unaffected by systemic administration of either GH or IGF-I. Continuous icv infusion of GH (1 microgram/h for 7 days) decreased GRH mRNA levels in both sexes, but did not alter SRIH mRNA levels. Continuous icv infusion of IGF-I (100 ng/h for 7 days) decreased GRH mRNA in both sexes. In contrast, SRIH mRNA levels were increased in both sexes. IGF-I decreased GRH mRNA levels at icv infusion rates of 100 and 300 ng/h and stimulated SRIH mRNA levels at infusion rates of 30 and 100 ng/h. Food intake was unaffected at these infusion rates. Changes in GRH and SRIH mRNA levels in response to systemic or central GH and IGF-I administration were similar in both sexes, except that the decrease in GRH mRNA levels produced by the icv infusion of IGF-I was greater in female than in male rats. The results provide evidence for a direct inhibitory feedback effect of GH in the central nervous system on the regulation of hypothalamic GRH gene expression that is independent of peripheral IGF-I. IGF-I feedback, in contrast, appears to

  1. Cold-Induced Thermogenesis and Inflammation-Associated Cold-Seeking Behavior Are Represented by Different Dorsomedial Hypothalamic Sites: A Three-Dimensional Functional Topography Study in Conscious Rats.

    Science.gov (United States)

    Wanner, Samuel P; Almeida, M Camila; Shimansky, Yury P; Oliveira, Daniela L; Eales, Justin R; Coimbra, Cândido C; Romanovsky, Andrej A

    2017-07-19

    In the past, we showed that large electrolytic lesions of the dorsomedial hypothalamus (DMH) promoted hypothermia in cold-exposed restrained rats, but attenuated hypothermia in rats challenged with a high dose of bacterial lipopolysaccharide (LPS) in a thermogradient apparatus. The goal of this study was to identify the thermoeffector mechanisms and DMH representation of the two phenomena and thus to understand how the same lesion could produce two opposite effects on body temperature. We found that the permissive effect of large electrolytic DMH lesions on cold-induced hypothermia was due to suppressed thermogenesis. DMH-lesioned rats also could not develop fever autonomically: they did not increase thermogenesis in response to a low, pyrogenic dose of LPS (10 μg/kg, i.v.). In contrast, changes in thermogenesis were uninvolved in the attenuation of the hypothermic response to a high, shock-inducing dose of LPS (5000 μg/kg, i.v.); this attenuation was due to a blockade of cold-seeking behavior. To compile DMH maps for the autonomic cold defense and for the cold-seeking response to LPS, we studied rats with small thermal lesions in different parts of the DMH. Cold thermogenesis had the highest representation in the dorsal hypothalamic area. Cold seeking was represented by a site at the ventral border of the dorsomedial nucleus. Because LPS causes both fever and hypothermia, we originally thought that the DMH contained a single thermoregulatory site that worked as a fever-hypothermia switch. Instead, we have found two separate sites: one that drives thermogenesis and the other, previously unknown, that drives inflammation-associated cold seeking.SIGNIFICANCE STATEMENT Cold-seeking behavior is a life-saving response that occurs in severe systemic inflammation. We studied this behavior in rats with lesions in the dorsomedial hypothalamus (DMH) challenged with a shock-inducing dose of bacterial endotoxin. We built functional maps of the DMH and found the strongest

  2. Expression of RFamide-Related Peptide-3 (RFRP-3) mRNA in Dorsomedial Hypothalamic Nucleus and KiSS-1 mRNA in Arcuate Nucleus of Rat during Pregnancy

    Science.gov (United States)

    Sabet Sarvestani, Fatemeh; Tamadon, Amin; Koohi-Hosseinabadi, Omid; Mohammadi Nezhad, Saeed; Rahmanifar, Farhad; Jafarzadeh Shirazi, Mohammad Reza; Tanideh, Nader; Moghadam, Ali; Niazi, Ali

    2014-01-01

    Background RFamide-related peptide-3 (RFRP-3) and kisspeptin (KiSS-1) are known to respectively inhibit and stimulate gonadotropin releasing hormone (GnRH) and lute- inizing hormone (LH) secretion in rat. The aim of the present study was to evaluate the relative mRNA expression of RFRP-3 and KiSS-1 in the hypothalamus of pregnant rats. Materials and Methods In a randomized controlled experimental study, the exact preg- nancy day of 18 Sprague-Dawley rats were confirmed using the vaginal smear method and were equally assigned to three groups of days 7, 14 and 21 of pregnancy. Four non- pregnant female rats were ovariectomized and assigned as the control group. All rats were decapitated, and the dorsomedial hypothalamic nucleus (DMH) and the arcuate nucleus (ARC) for detection of KiSS-1 mRNA were separated from their hypothalamus to detect RFRP-3 and KiSS-1 mRNA respectively. Then, their relative expressions were compared between control and pregnant groups using real-time polymerase chain reac- tion (PCR). Results The relative expression of RFRP-3 mRNA in DMH did not change significantly during pregnancy (p>0.01). However, the relative expression of KiSS-1 mRNA in ARC was at its highest in day 7 of pregnancy and decreased until day 21 of pregnancy (p<0.01). Conclusion Decrease in GnRH and LH secretion during the pregnancy of rat may be controlled by constant expression of RFRP-3 mRNA and reduced expression of KiSS-1 mRNA in hypothalamus. PMID:25379163

  3. Expression of RFamide-Related Peptide-3 (RFRP-3) mRNA in Dorsomedial Hypothalamic Nucleus and KiSS-1 mRNA in Arcuate Nucleus of Rat during Pregnancy.

    Science.gov (United States)

    Sabet Sarvestani, Fatemeh; Tamadon, Amin; Koohi-Hosseinabadi, Omid; Mohammadi Nezhad, Saeed; Rahmanifar, Farhad; Jafarzadeh Shirazi, Mohammad Reza; Tanideh, Nader; Moghadam, Ali; Niazi, Ali

    2014-10-01

    RFamide-related peptide-3 (RFRP-3) and kisspeptin (KiSS-1) are known to respectively inhibit and stimulate gonadotropin releasing hormone (GnRH) and lute- inizing hormone (LH) secretion in rat. The aim of the present study was to evaluate the relative mRNA expression of RFRP-3 and KiSS-1 in the hypothalamus of pregnant rats. In a randomized controlled experimental study, the exact preg- nancy day of 18 Sprague-Dawley rats were confirmed using the vaginal smear method and were equally assigned to three groups of days 7, 14 and 21 of pregnancy. Four non- pregnant female rats were ovariectomized and assigned as the control group. All rats were decapitated, and the dorsomedial hypothalamic nucleus (DMH) and the arcuate nucleus (ARC) for detection of KiSS-1 mRNA were separated from their hypothalamus to detect RFRP-3 and KiSS-1 mRNA respectively. Then, their relative expressions were compared between control and pregnant groups using real-time polymerase chain reac- tion (PCR). The relative expression of RFRP-3 mRNA in DMH did not change significantly during pregnancy (p>0.01). However, the relative expression of KiSS-1 mRNA in ARC was at its highest in day 7 of pregnancy and decreased until day 21 of pregnancy (p<0.01). Decrease in GnRH and LH secretion during the pregnancy of rat may be controlled by constant expression of RFRP-3 mRNA and reduced expression of KiSS-1 mRNA in hypothalamus.

  4. Young adult-specific hyperphagia in diabetic Goto-kakizaki rats is associated with leptin resistance and elevation of neuropeptide Y mRNA in the arcuate nucleus.

    Science.gov (United States)

    Maekawa, F; Fujiwara, K; Kohno, D; Kuramochi, M; Kurita, H; Yada, T

    2006-10-01

    The present study aimed to examine whether hyperphagia, which is frequently observed in type 1 diabetic patients and model animals, also occurs in type 2 diabetic Goto-Kakizaki (GK) rats and, if so, to explore underlying abnormalities in the hypothalamus. GK rats at postnatal weeks 6-12, compared to control Wistar rats, exhibited hyperphagia, hyperglycaemia, hyperleptinemia and increased visceral fat accumulation, whereas body weight was unaltered. The ability of leptin to suppress feeding was reduced in GK rats compared to Wistar rats of these ages. In GK rats, leptin-induced phosphorylation of signal transducer and activator of transcription 3 was significantly reduced in the cells of the hypothalamic arcuate nucleus (ARC), but not of the ventromedial hypothalamus, whereas the mRNA level of functional leptin receptor was unaltered. By real-time polymerase chain reaction and in situ hybridisation, mRNA levels of neuropeptide Y, but not pro-opiomelanocortin and galanin-like peptide, were significantly increased in the ARC of GK rats at 11 weeks, but not 26 weeks. Following i.c.v. injection of a NPY Y1 antagonist, 1229U91, the amount of food intake in GK rats was indistinguishable from that in Wistar rats, thus eliminating the hyperphagia of GK rats. These results demonstrate that young adult GK rats display hyperphagia in association with leptin resistance and increased NPY mRNA level in the ARC.

  5. Enhancement of BDNF Concentration and Restoration of the Hypothalamic-Pituitary-Adrenal Axis Accompany Reduced Depressive-Like Behaviour in Stressed Ovariectomised Rats Treated with Either Tualang Honey or Estrogen

    Directory of Open Access Journals (Sweden)

    Badriya Al-Rahbi

    2014-01-01

    Full Text Available A possible interaction between glucocorticoids and estrogen-induced increases in brain-derived-neurotrophic factor (BDNF expression in enhancing depressive-like behaviour has been documented. Here we evaluated the effects of Tualang honey, a phytoestrogen, and 17β-estradiol (E2 on the depressive-like behaviour, stress hormones, and BDNF concentration in stressed ovariectomised (OVX rats. The animals were divided into six groups: (i nonstressed sham-operated control, (ii stressed sham-operated control, (iii nonstressed OVX, (iv stressed OVX, (v stressed OVX treated with E2 (20 μg daily, sc, and (vi stressed OVX treated with Tualang honey (0.2 g/kg body weight daily, orally. Two months after surgery, the animals were subjected to social instability stress procedure followed by forced swimming test. Struggling time, immobility time, and swimming time were scored. Serum adrenocorticotropic hormone (ACTH and corticosterone levels, and the BDNF concentration were determined using commercially available ELISA kits. Stressed OVX rats displayed increased depressive-like behaviour with significantly increased serum ACTH and corticosterone levels, while the BDNF concentration was significantly decreased compared to other experimental groups. These changes were notably reversed by both E2 and Tualang honey. In conclusion, both Tualang honey and E2 mediate antidepressive-like effects in stressed OVX rats, possibly acting via restoration of hypothalamic-pituitary-adrenal axis and enhancement of the BDNF concentration.

  6. Lucid dreaming and ventromedial versus dorsolateral prefrontal task performance.

    Science.gov (United States)

    Neider, Michelle; Pace-Schott, Edward F; Forselius, Erica; Pittman, Brian; Morgan, Peter T

    2011-06-01

    Activity in the prefrontal cortex may distinguish the meta-awareness experienced during lucid dreams from its absence in normal dreams. To examine a possible relationship between dream lucidity and prefrontal task performance, we carried out a prospective study in 28 high school students. Participants performed the Wisconsin Card Sort and Iowa Gambling tasks, then for 1 week kept dream journals and reported sleep quality and lucidity-related dream characteristics. Participants who exhibited a greater degree of lucidity performed significantly better on the task that engages the ventromedial prefrontal cortex (the Iowa Gambling Task), but degree of lucidity achieved did not distinguish performance on the task that engages the dorsolateral prefrontal cortex (the Wisconsin Card Sort Task), nor did it distinguish self-reported sleep quality or baseline characteristics. The association between performance on the Iowa Gambling Task and lucidity suggests a connection between lucid dreaming and ventromedial prefrontal function. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. 下丘脑室旁核组胺H3受体对哮喘大鼠下丘脑-垂体-肾上腺轴功能的调控%Effect of histamine H3 receptor in the hypothalamic paraventricular nuclei on hypothalamic-pituitary-adrenal axis in rats with asthma

    Institute of Scientific and Technical Information of China (English)

    季吉; 董榕

    2011-01-01

    Objective: To determine whether histamine H3 receptor in the hypothalamic paraventricular nuclei (PVN) regulates the function of hypothalamic-pituitary-adrenal (HPA) axis in rats with asthma. Method: Rat model for asthma was established by Elwood's methods. A stainless steel jacket was implanted into the PVN using a technique of central three-dimensional position, and R(α)-methylhistamine [R-(α)-MeHA, a H3 receptor agonist] 2 μg or thioperamide (a H3 receptor antagonist) 5 μg was injected into the PVN. Levels of histamine in PVN were detected by high-performance liquid chromatography, and the concentrations of CRH in median eminence, ACTH and CORT in plasma were detected by the radioimmunoassay. Relative levels of IL-10 in both hypothalataus tissue and plasma were measred by double-ligand-linked immunosorbent assay. Result: Levels of histamine in PVN decreased significantly, whereas the concentrations of CRH in median eminence, ACTH and CORT in plasma and the levels of IL-lO in both hypothalamus tissue and plasma were all increased significantly in acute episode asthms rats with treatment of R-(α)-MeHA compared with control rats, and these responses were blocked by treatment of thioperamide, a H3 receptors specific antagonist. Conclusion: Specific activation histamine H3 receptors in PVN can improve the function of HPA in rats with asthma.%目的:探讨哮喘大鼠下丘脑室旁核(paraventricular nuclei,PVN)内组胺H3受体对下丘脑-垂体-肾上腺轴(HPA)功能的调控.方法:根据Elwood方法,制备哮喘模型.采用中枢立体定位技术,在PVN内微量注射组胺H3受体激动剂R-(α)-甲基组胺[R-(α)-methylhistamine,R-(α)-MeHA]2 μg或组胺H3受体拮抗剂Thioperamide 5 μg,注射药物体积均为1μl.高效液相色谱法检测PVN内组胺含量;放射免疫分析方法检测正中隆起中促肾上腺皮质激素释放激素(CRH)和外周血中促肾上腺皮质激素(ACTH)、皮质酮(CORT)含量;酶联免疫吸附法(ELISA

  8. Tyrosine hydroxylase is short-term regulated by the ubiquitin-proteasome system in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats: possible implications in hypertension.

    Directory of Open Access Journals (Sweden)

    Nadia A Congo Carbajosa

    Full Text Available Aberrations in the ubiquitin-proteasome system (UPS are implicated in the pathogenesis of various diseases. Tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamines biosynthesis, is involved in hypertension development. In this study we investigated whether UPS regulated TH turnover in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats (SHR and whether this system was impaired in hypertension. PC12 cells were exposed to proteasome or lysosome inhibitors and TH protein level evaluated by Western blot. Lactacystin, a proteasome inhibitor, induced an increase of 86 ± 15% in TH levels after 30 min of incubation, then it started to decrease up to 6 h to reach control levels and finally it rose up to 35.2 ± 8.5% after 24 h. Bafilomycin, a lysosome inhibitor, did not alter TH protein levels during short times, but it increased TH by 92 ± 22% above basal after 6 h treatment. Before degradation proteasome substrates are labeled by conjugation with ubiquitin. Efficacy of proteasome inhibition on TH turnover was evidenced by accumulation of ubiquitinylated TH after 30 min. Further, the inhibition of proteasome increased the quantity of TH phosphorylated at Ser40, which is essential for TH activity, by 2.7 ± 0.3 fold above basal. TH protein level was upregulated in neurons from hypothalami and brainstem of SHR when the proteasome was inhibited during 30 min, supporting that neuronal TH is also short-term regulated by the proteasome. Since the increased TH levels reported in hypertension may result from proteasome dysfunction, we evaluate proteasome activity. Proteasome activity was significantly reduced by 67 ± 4% in hypothalamic and brainstem neurons from SHR while its protein levels did not change. Present findings show that TH is regulated by the UPS. The impairment in proteasome activity observed in SHR neurons may be one of the causes of the increased TH protein levels reported in hypertension.

  9. Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat Part 2: Effects on reproductive parameters, on sex behavior, on memory retention and on hypothalamic expression of aromatase and 5alpha-reductases in the offspring.

    Science.gov (United States)

    Colciago, A; Casati, L; Mornati, O; Vergoni, A V; Santagostino, A; Celotti, F; Negri-Cesi, P

    2009-08-15

    The gender-specific expression pattern of aromatase and 5alpha-reductases (5alpha-R) during brain development provides neurons the right amount of estradiol and DHT to induce a dimorphic organization of the structure. Polychlorinated biphenyls (PCBs) are endocrine disruptive pollutants; exposure to PCBs through placental transfer and breast-feeding may adversely affect the organizational action of sex steroid, resulting in long-term alteration of reproductive neuroendocrinology. The study was aimed at: a) evaluating the hypothalamic expression of aromatase, 5alpha-R1 and 5alpha-R2 in fetuses (GD20), infant (PN12), weaning (PN21) and young adult (PN60) male and female rats exposed to PCBs during development; b) correlating these parameters with the time of testicular descent, puberty onset, estrous cyclicity and copulatory behavior; c) evaluating possible alterations of some non reproductive behaviors (locomotion, learning and memory, depression/anxiety behavior). A reconstituted mixture of four indicator congeners (PCB 126, 138, 153 and 180) was injected subcutaneously to dams at the dose of 10 mg/kg daily from GD15 to GD19 and then twice a week till weanling. The results indicated that developmental PCB exposure produced important changes in the dimorphic hypothalamic expression of both aromatase and the 5alpha-Rs, which were still evident in adult animals. We observed that female puberty onset occurs earlier than in control animals without cycle irregularity, while testicular descent in males was delayed. A slight but significant impairment of sexual behavior and an important alteration in memory retention were also noted specifically in males. We conclude that PCBs might affect the dimorphic neuroendocrine control of reproductive system and of other neurobiological processes.

  10. ICV vs. VMH injection of leptin: comparative effects on hypothalamic gene expression.

    Science.gov (United States)

    Ambati, Suresh; Duan, Jiuhua; Choi, Yang-Ho; Hartzell, Diane L; Della-Fera, Mary Anne; Baile, Clifton A

    2009-01-23

    Leptin regulates feeding behavior and body weight by binding to its receptors localized in specific areas of the hypothalamus. Leptin injected twice daily for 4 days either into the right ventromedial hypothalamus (VMH) or into the right lateral cerebral ventricle (ICV) and using Real-Time Taqman RT-PCR, mRNA expression levels of selected genes in the arcuate nucleus-median eminence (ARC-ME) complex were quantitatively measured. Expression of selected genes from the ipsi- vs. contralateral VMH areas in rats injected with leptin into the VMH was also compared. VMH injections of leptin increased ARC-ME mRNAs of proopiomelanocortin (POMC), 27.3% (p<0.05); gamma-aminobutyric acid A receptor (GABRD), 89.3% (p<0.01); and thyrotropin-releasing hormone (TRH), 57.7% (p<0.01); and decreased janus kinase 2 (JAK2), 44.4% (p<0.001); suppressor of cytokine signaling 3 (SOCS3), 86.6% (p<0.001); signal transducer and activator of transcription 3 (STAT3), 46.8% (p<0.01); tyrosine hydroxylase (TH), 51.1% (p<0.001); prostaglandin E synthase (PTGES), 96.5% (p<0.001); tumor necrosis factor-alpha (TNF-alpha), 47% (p<0.01); and secretin, 55.4% (p<0.001). Only GABRD, 76.6% (p<0.01) and SCT, 64.9% (p<0.01) were up-regulated in the hypothalamic ARC-ME of rats with ICV leptin injections. VMH injections of leptin induced identical reductions in expression levels of CART, SOCS3, PTGES, and TNF-alpha in both VMH areas; except TH mRNA, whose expression was lowered ipsilaterally. Food intake, body and fat pad weights and serum insulin and leptin were also decreased in rats given leptin through VMH. This study suggests that leptin either unilateral exposure through VMH or bilateral exposure through ICV injections induces divergent ARC-ME gene profiles.

  11. Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA.

    Science.gov (United States)

    López, Miguel; Lelliott, Christopher J; Tovar, Sulay; Kimber, Wendy; Gallego, Rosalía; Virtue, Sam; Blount, Margaret; Vázquez, Maria J; Finer, Nick; Powles, Trevor J; O'Rahilly, Stephen; Saha, Asish K; Diéguez, Carlos; Vidal-Puig, Antonio J

    2006-05-01

    Fatty acid metabolism in the hypothalamus has recently been shown to regulate feeding. The selective estrogen receptor modulator tamoxifen (TMX) exerts a potent anorectic effect. Here, we show that the anorectic effect of TMX is associated with the accumulation of malonyl-CoA in the hypothalamus and inhibition of fatty acid synthase (FAS) expression specifically in the ventromedial nucleus of the hypothalamus (VMN). Furthermore, we demonstrate that FAS mRNA expression is physiologically regulated by fasting and refeeding in the VMN but not in other hypothalamic nuclei. Thus, the VMN appears to be the hypothalamic site where regulation of FAS and feeding converge. Supporting the potential clinical relevance of these observations, reanalysis of a primary breast cancer prevention study showed that obese women treated with TMX gained significantly less body weight over a 6-year period than obese women given placebo. The finding that TMX can modulate appetite through alterations in FAS expression and malonyl-CoA levels suggests a link between hypothalamic sex steroid receptors, fatty acid metabolism, and feeding behavior.

  12. Effect of a high-fat--high-fructose diet, stress and cinnamon on central expression of genes related to immune system, hypothalamic-pituitary-adrenocortical axis function and cerebral plasticity in rats.

    Science.gov (United States)

    Marissal-Arvy, Nathalie; Batandier, Cécile; Dallennes, Julien; Canini, Frédéric; Poulet, Laurent; Couturier, Karine; Hininger-Favier, Isabelle; Moisan, Marie-Pierre; Roussel, Anne-Marie; Mormède, Pierre

    2014-04-14

    The intake of a high-fat/high-fructose (HF/HFr) diet is described to be deleterious to cognitive performances, possibly via the induction of inflammatory factors. An excess of glucocorticoids is also known to exert negative effects on cerebral plasticity. In the present study, we assessed the effects of an unbalanced diet on circulating and central markers of inflammation and glucocorticoid activity, as well as their reversal by dietary cinnamon (CN) supplementation. A group of male Wistar rats were subjected to an immune challenge with acute lipopolysaccharide under a HF/HFr or a standard diet. Another group of Wistar rats were fed either a HF/HFr or a control diet for 12 weeks, with or without CN supplementation, and with or without restraint stress (Str) application before being killed. We evaluated the effects of such regimens on inflammation parameters in the periphery and brain and on the expression of actors of brain plasticity. To assess hypothalamic-pituitary-adrenocortical axis activity, we measured the plasma concentrations of corticosterone and the expression of central corticotrophin-releasing hormone, mineralocorticoid receptor, glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase. We found that the HF/HFr diet induced the expression of cytokines in the brain, but only after an immune challenge. Furthermore, we observed the negative effects of Str on the plasma concentrations of corticosterone and neuroplasticity markers in rats fed the control diet but not in those fed the HF/HFr diet. Additionally, we found that CN supplementation exerted beneficial effects under the control diet, but that its effects were blunted or even reversed under the HF/HFr diet. CN supplementation could be beneficial under a standard diet. [corrected].

  13. Effects of repeated ether stress on the hypothalamic-pituitary-testes axis in adult rats with special reference to inhibin secretion.

    Science.gov (United States)

    Tohei, A; Tomabechi, T; Mamada, M; Akai, M; Watanabe, G; Taya, K

    1997-05-01

    Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

  14. Age-related alterations in hypothalamic kisspeptin, neurokinin B, and dynorphin neurons and in pulsatile LH release in female and male rats.

    Science.gov (United States)

    Kunimura, Yuyu; Iwata, Kinuyo; Ishigami, Akihito; Ozawa, Hitoshi

    2017-02-01

    Pulsatile secretion of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) decreases during aging. Kisspeptin (encoded by Kiss1) neurons in the arcuate nucleus coexpress neurokinin B (Tac3) and dynorphin (Pdyn) and are critical for regulating the GnRH/LH pulse. We therefore examined kisspeptin neurons by histochemistry and pulsatile LH release in rats aged 2-3 (Young), 12-13 (Young-Middle), 19-22 (Late-Middle), and 24-26 (Old) months. Total LH concentrations, sampled for 3 hours, decreased in both sexes with aging. In females, numbers of Tac3 and Pdyn neurons were significantly reduced in all aging rats, and numbers of Kiss1 neurons were significantly reduced in Late-Middle and Old rats. In males, numbers of all 3 neuron-types were significantly decreased in all aging rats. GnRH agonist induced LH release in all animals; however, the increased LH concentration in all aging rats was less than that in Young rats. These results suggest that expression of each gene in kisspeptin neurons may be controlled individually during aging, and that reduction of their expression or change in pituitary responsiveness may cause attenuated pulsatile LH secretion.

  15. Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase.

    Science.gov (United States)

    Martínez de Morentin, Pablo B; Whittle, Andrew J; Fernø, Johan; Nogueiras, Rubén; Diéguez, Carlos; Vidal-Puig, Antonio; López, Miguel

    2012-04-01

    Smokers around the world commonly report increased body weight after smoking cessation as a major factor that interferes with their attempts to quit. Numerous controlled studies in both humans and rodents have reported that nicotine exerts a marked anorectic action. The effects of nicotine on energy homeostasis have been mostly pinpointed in the central nervous system, but the molecular mechanisms controlling its action are still not fully understood. The aim of this study was to investigate the effect of nicotine on hypothalamic AMP-activated protein kinase (AMPK) and its effect on energy balance. Here we demonstrate that nicotine-induced weight loss is associated with inactivation of hypothalamic AMPK, decreased orexigenic signaling in the hypothalamus, increased energy expenditure as a result of increased locomotor activity, increased thermogenesis in brown adipose tissue (BAT), and alterations in fuel substrate utilization. Conversely, nicotine withdrawal or genetic activation of hypothalamic AMPK in the ventromedial nucleus of the hypothalamus reversed nicotine-induced negative energy balance. Overall these data demonstrate that the effects of nicotine on energy balance involve specific modulation of the hypothalamic AMPK-BAT axis. These targets may be relevant for the development of new therapies for human obesity.

  16. Regulation of Energy Balance via BDNF Expressed in Nonparaventricular Hypothalamic Neurons.

    Science.gov (United States)

    Yang, Haili; An, Juan Ji; Sun, Chao; Xu, Baoji

    2016-05-01

    Brain-derived neurotrophic factor (BDNF) expressed in the paraventricular hypothalamus (PVH) has been shown to play a key role in regulating energy intake and energy expenditure. BDNF is also expressed in other hypothalamic nuclei; however, the role in the control of energy balance for BDNF produced in these structures remains largely unknown. We found that deleting the Bdnf gene in the ventromedial hypothalamus (VMH) during embryogenesis using the Sf1-Cre transgene had no effect on body weight in mice. In contrast, deleting the Bdnf gene in the adult VMH using Cre-expressing virus led to significant hyperphagia and obesity. These observations indicate that the lack of a hyperphagia phenotype in the Sf1-Cre/Bdnf mutant mice is likely due to developmental compensation. To investigate the role of BDNF expressed in other hypothalamic areas, we employed the hypothalamus-specific Nkx2.1-Cre transgene to delete the Bdnf gene. We found that the Nkx2.1-Cre transgene could abolish BDNF expression in many hypothalamic nuclei, but not in the PVH, and that the resulting mutant mice developed modest obesity due to reduced energy expenditure. Thus, BDNF produced in the VMH plays a role in regulating energy intake. Furthermore, BDNF expressed in hypothalamic areas other than PVH and VMH is also involved in the control of energy expenditure.

  17. Differential effects of inhalation exposure to PM2.5 on hypothalamic monoamines and corticotrophin releasing hormone in lean and obese rats.

    Science.gov (United States)

    Balasubramanian, Priya; Sirivelu, Madhu P; Weiss, Kathryn A; Wagner, James G; Harkema, Jack R; Morishita, Masako; Mohankumar, P S; Mohankumar, Sheba M J

    2013-05-01

    Acute exposure to airborne pollutants, especially particulate matter (PM2.5) is known to increase hospital admissions for cardiovascular conditions, increase cardiovascular related mortality and predispose the elderly and obese individuals to cardiovascular conditions. The mechanisms by which PM2.5 exposure affects the cardiovascular system is not clear. Since the autonomic system plays an important role in cardiovascular regulation, we hypothesized that PM2.5 exposure most likely activates the paraventricular nucleus (PVN) of the hypothalamus to cause an increase in sympathetic nervous system and/or stress axis activity. We also hypothesized that these changes may be sustained in obese rats predisposing them to higher cardiovascular risk. To test this, adult male Brown Norway (BN) rats were subjected to one day or three days of inhalation exposures to filtered air (FA) or concentrated air particulate (CAP) derived from ambient PM2.5. Corpulent JCR-LA rats were exposed to FA or CAP for four days. Animals were sacrificed 24h after the last inhalation exposure. Their brains were removed, frozen and sectioned. The PVN and median eminence (ME) were microdissected. PVN was analyzed for norepinephrine (NE), dopamine (DA) and 5-hydroxy-indole acetic acid (5-HIAA) levels using HPLC-EC. ME was analyzed for corticotrophin releasing hormone (CRH) levels by ELISA. One day exposure to CAP increased NE levels in the PVN and CRH levels in the ME of BN rats. Repeated exposures to CAP did not affect NE levels in the PVN of BN rats, but increased NE levels in JCR/LA rats. A similar pattern was observed with 5-HIAA levels. DA levels on the other hand, were unaffected in both BN and JCR/LA strains. These data suggest that repeated exposures to PM2.5 continue to stimulate the PVN in obese animals but not lean rats.

  18. Time course of lithium-induced alterations in renal and endocrine function in normal and Brattleboro rats with hypothalamic diabetes insipidus.

    Science.gov (United States)

    Balment, R J; Jones, I C; Henderson, I W

    1977-04-01

    1. A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin. 2. During the first 24 h, Li-supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li-supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities. 3. The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li-supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually re-established, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement. 4. Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li-supplement. 5. Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period. 6. Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals were increased. 7. It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.

  19. Affective ambiguity for a group recruits ventromedial prefrontal cortex.

    Science.gov (United States)

    Simmons, Alan; Stein, Murray B; Matthews, Scott C; Feinstein, Justin S; Paulus, Martin P

    2006-01-15

    Affective appraisal often involves processing complex and ambiguous stimuli, such as the mood of a group people. However, affective neuroimaging research often uses individual faces as stimuli when exploring the neural circuitry involved in social appraisal. Results from studies using single face paradigms may not generalize to settings where multiple faces are simultaneously processed. The goal of the current study was to use a novel task that presents groups of affective faces to probe the medial prefrontal cortex (PFC), a region that is critically involved in appraisal of ambiguous affective stimuli, in healthy volunteers. In the current study, 27 subjects performed the Wall of Faces (WOF) task in which multiple matrices of faces were briefly presented during functional MRI. Subjects were asked to decide whether there were more angry or happy faces (emotional decision) or whether there were more male or female faces (gender decision). In each condition, the array contained either an equal (ambiguous trials) or an unequal (unambiguous trials) distribution of one affect or gender. Ambiguous trials relative to unambiguous trials activated regions implicated in conflict monitoring and cognitive control, including the dorsal anterior cingulate cortex (ACC), dorsolateral PFC, and posterior parietal cortex. When comparing ambiguous affective decisions with ambiguous gender decisions, the ventromedial PFC (including the ventral ACC) was significantly more active. This supports the dissociation of the ACC into dorsal cognitive and ventral affective divisions, and suggests that the ventromedial PFC may play a critical role in appraising affective tone in a complex display of multiple human faces.

  20. Reversible antisocial behavior in ventromedial prefrontal lobe epilepsy.

    Science.gov (United States)

    Trebuchon, Agnès; Bartolomei, Fabrice; McGonigal, Aileen; Laguitton, Virginie; Chauvel, Patrick

    2013-11-01

    Frontal lobe dysfunction is known to be associated with impairment in social behavior. We investigated the link between severe pharmacoresistant frontal lobe epilepsy and antisocial trait. We studied four patients with pharmacoresistant epilepsy involving the prefrontal cortex, presenting abnormal interictal social behavior. Noninvasive investigations (video-EEG, PET, MRI) and intracerebral recording (stereoelectroencephalography (SEEG)) were performed as part of a presurgical assessment. Comprehensive psychiatric and cognitive evaluation was performed pre- and postoperatively for frontal lobe epilepsy, with at least 7years of follow-up. All patients shared a characteristic epilepsy pattern: (1) chronic severe prefrontal epilepsy with daily seizures and (2) an epileptogenic zone as defined by intracerebral recording involving the anterior cingulate cortex, ventromedial PFC, and the posterior part of the orbitofrontal cortex, with early propagation to contralateral prefrontal and ipsilateral medial temporal structures. All patients fulfilled the diagnostic criteria (DSM-IV) of antisocial personality disorder, which proved to be reversible following seizure control. Pharmacoresistant epilepsy involving a prefrontal network is associated with antisocial personality. We hypothesize that the occurrence of frequent seizures in this region over a prolonged period produces functional damage leading to impaired prefrontal control of social behavior. This functional damage is reversible since successful epilepsy surgery markedly improved antisocial behavior in these patients. The results are in line with previous reports of impairment of social and moral behavior following ventromedial frontal lobe injury.

  1. A model for chronic, intrahypothalamic thyroid hormone administration in rats

    NARCIS (Netherlands)

    Zhang, Z; Bisschop, P H; Foppen, E; van Beeren, H C; Kalsbeek, A; Boelen, A; Fliers, E

    2016-01-01

    In addition to the direct effects of thyroid hormone (TH) on peripheral organs, recent work showed metabolic effects of TH on the liver and brown adipose tissue via neural pathways originating in the hypothalamic paraventricular and ventromedial nucleus (PVN and VMH). So far, these experiments focus

  2. Maternal caloric restriction implemented during the preconceptional and pregnancy period alters hypothalamic and hippocampal endocannabinoid levels at birth and induces overweight and increased adiposity at adulthood in male rat offspring

    Directory of Open Access Journals (Sweden)

    MARÍA TERESA RAMÍREZ-LÓPEZ

    2016-11-01

    Full Text Available Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet during pre-gestational and gestational periods on a neonatal outcomes, b endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth, c metabolism-related parameters, and d behavior in adult male offspring. We found that calorie-restricted dams tended to have a reduced litter size, although the offspring showed normal weight at birth. Pups from calorie-restricted dams also exhibited a strong decrease in the levels of anandamide (AEA, 2-arachidonoylglycerol (2-AG, arachidonic acid (AA and palmitoylethanolamide (PEA in the hypothalamus at birth. Additionally, pups from diet-restricted dams displayed reduced levels of AEA in the hippocampus without significant differences in the olfactory bulb. Moreover, offspring exhibited increased weight gain, body weight and adiposity in adulthood as well as increased anxiety-related responses. We propose that endocannabinoid signaling is altered by a maternal caloric restriction implemented during the preconceptional and pregnancy periods, which might lead to modifications of the hypothalamic and hippocampal circuits, potentially contributing to the long-term effects found in the adult offspring.

  3. Maternal Caloric Restriction Implemented during the Preconceptional and Pregnancy Period Alters Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Overweight and Increased Adiposity at Adulthood in Male Rat Offspring

    Science.gov (United States)

    Ramírez-López, María Teresa; Vázquez, Mariam; Bindila, Laura; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosarío Noemí; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Ouro, Daniel; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Rodríguez de Fonseca, Fernando

    2016-01-01

    Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet) during pre-gestational and gestational periods on: (a) neonatal outcomes; (b) endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth; (c) metabolism-related parameters; and (d) behavior in adult male offspring. We found that calorie-restricted dams tended to have a reduced litter size, although the offspring showed normal weight at birth. Pups from calorie-restricted dams also exhibited a strong decrease in the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), arachidonic acid (AA) and palmitoylethanolamide (PEA) in the hypothalamus at birth. Additionally, pups from diet-restricted dams displayed reduced levels of AEA in the hippocampus without significant differences in the olfactory bulb. Moreover, offspring exhibited increased weight gain, body weight and adiposity in adulthood as well as increased anxiety-related responses. We propose that endocannabinoid signaling is altered by a maternal caloric restriction implemented during the preconceptional and pregnancy periods, which might lead to modifications of the hypothalamic and hippocampal circuits, potentially contributing to the long-term effects found in the adult offspring. PMID:27847471

  4. Neurotensin releases norepinephrine differentially from perfused hypothalamus of sated and fasted rat

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T.F.; Rezvani, A.H.; Hepler, J.R.; Myers, R.D.

    1987-01-01

    The central injection of neurotensin (NT) has been reported to attenuate the intake of food in the fasted animal. To determine whether endogenous norepinephrine (NE) is involved in the satiating effect of NT, the in vivo activity of NE in circumscribed sites in the hypothalamus of the unanesthetized rat was examined. Bilateral guide tubes for push-pull perfusion were implanted stereotaxically to rest permanently above one of several intended sites of perfusion, which included the paraventricular nucleus (PVN), ventromedial nucleus (VMN), and the lateral hypothalamic (LH) area. After endogenous stores of NE at a specific hypothalamic locus were radiolabeled by microinjection of 0.02-0.5 ..mu..Ci of (/sup 3/H)NE, an artificial cerebrospinal fluid was perfused at the site at a rate of 20 ..mu..l/min over successive intervals of 5.0 min. When 0.05 or 0.1 ..mu..g/..mu..l NT was added to the perfusate, the peptide served either to enhance or educe the local release of NE at 50% of the sites of perfusion. In these experiments, the circumscribed effect of NT on the characteristics of catecholamine efflux depended entirely on the state of hunger or satiety of the rat. That is, when NT was perfused in the fully satiated rat, NE release was augmented within the PVn or VMN; conversely, NE release was inhibited in the LH. in the animal fasted for 18-22 h, NT exerted an opposite effect on the activity of NE within the same anatomical loci in that the efflux of NE was enhanced in the LH but attenuated or unaffected in the PVN or VMN. Taken together, these observations provide experimental support for the view-point that NT could act as a neuromodulator of the activity of hypothalamic noradrenergic neurons that are thought to play a functional role in the regulation of food intake.

  5. Dual projections of single orexin- or CART-immunoreactive, lateral hypothalamic neurons to the paraventricular thalamic nucleus and nucleus accumbens shell in the rat: Light microscopic study.

    Science.gov (United States)

    Lee, Eun Y; Lee, Hyun S

    2016-03-01

    The paraventricular thalamic nucleus (PVT) is a major relay station to the limbic forebrain areas such as the nucleus accumbens shell (AcbSh). Both PVT and AcbSh are known to receive feeding/arousal-related peptidergic fibers including orexin (ORX) and cocaine- and amphetamine-regulated transcript (CART) peptide. In the first series of experiments, we examined the peptidergic fiber distribution in the AcbSh; the density of ORX (or CART) fibers in the AcbSh was substantially lower than that in the PVT. At the light microscopic level, ORX (or CART) terminals formed close appositions to choline acetyltransferase (ChAT)-, glutamate decarboxylase (GAD)-, or enkephalin (Enk)-immunoreactive neuronal elements in the AcbSh. In the second series of experiments, we addressed the question of whether single ORX (or CART) cells in the hypothalamus provided divergent axon collaterals to the PVT and AcbSh. ORX neurons with dual projections were found in the medial, central, and lateral subdivisions of the lateral hypothalamus (LH), which amounted to an average of 1.6% of total ORX cells. CART neurons with divergent axon collaterals were observed in the LH, zona incerta, dorsal hypothalamic area, and retrochiasmatic nucleus, which represented a mean of 2.5% of total CART cells. None of arcuate CART cells sent dual projections. These data suggested that a portion of ORX (or CART) neurons in the hypothalamus, via divergent axon collaterals, might concurrently modulate the activity of PVT and AcbSh cells to affect feeding and drug-seeking behaviors.

  6. Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats

    Science.gov (United States)

    Sun, Wenyan; Yan, Chunhong; Frost, Bess; Wang, Xin; Hou, Chen; Zeng, Mengqi; Gao, Hongli; Kang, Yuming; Liu, Jiankang

    2016-01-01

    High blood pressure, or “hypertension,” is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension. PMID:27713551

  7. Lack of sensorial innervation in the newborn female rats affects the activity of hypothalamic monoaminergic system and steroid hormone secretion during puberty.

    Science.gov (United States)

    Quiróz, Ubaldo; Morales-Ledesma, Leticia; Morán, Carolina; Trujillo, Angélica; Domínguez, Roberto

    2014-06-01

    There is evidence that sensory innervation plays a role regulating ovarian functions, including fertility.Since sensory denervation by means of capsaicin in newborn female rats results in a lower response togonadotropins, the present study analyzed the effects that sensory denervation by means of capsaicin in neonatal rats has on the concentration of monoamines in the anterior(AH) and medium (MH) hypothalamus, and on steroid hormone levels in serum. Groups of newborn female rats were injected subcutaneously with capsaicin and killed at 10, 20, and 30 days of age and on the first vaginal estrous.The concentrations of noradrenaline, dopamine, serotonin(5-HT), and their metabolites in the AH and MH were measured using HPLC, and the levels of estradiol (E),progesterone (P), testosterone (T), FSH, and luteinizing hormone using radioimmunoanalysis. The results show thatat 20 days of age, capsaicin-treated rats have lowernoradrenergic and serotonergic activities in the AH, and that the dopaminergic activity was lower in the MH. These results suggest that the sensorial system connections within the monoaminergic systems of the AH and MH are different.Capsaicin-treated animals had lower T, E, and P levels than in the control group, suggesting that the lower activity in the AH monoaminergic system and lower hormonesecretion could be explained by the blockade of information mediated by the sensory innervation (probably substance P), mainly between the ovary and the AH.

  8. Hypothalamic neuronal targets activated by neuropeptide S%神经肽S激活下丘脑靶神经元的分布

    Institute of Scientific and Technical Information of China (English)

    闫琼; 邵玉峰; 赵鹏; 孔祥攀; 姜信诚; 侯一平

    2013-01-01

    Objective To identify the distributions of neuropeptide S (NPS) induced neuronal activation in hypothalamus in rats because NPS,a newly identified neuropeptide,was presumed to activate the hypothalamic neurons through its receptors to participate hypothalamic physiological regulation.Methods Fos immunohistochemistry was employed to label the activated neurons following intracerebroventricular (i.c.v.) injection of NPS (1 nmol,n=6) and saline (n=6).The distribution and number of fos immunoreactive (-IR) neurons in the hypothalamus were observed,counted and statistically analyzed.Results The number of fos-IR neurons induced by NPS in the suprachiasmatic nucleus,paraventricular nucleus,dorsomedial hypothalamic nucleus,ventromedial hypothalamic nucleus,arcuate nucleus,perifornical nucleus,and the ventral and dorsal tuberomammillary nuclei and lateral hypothalamic area were respectively increased by 322%,108%,274%,126%,267%,520%,641%,586% and 378% compared with saline (P <0.0001).Conclusion NPS-induced a large number of active neurons in the hypothalamus suggest that NPS is involved in hypothalamic physiological regulation including sleep-wake cycle,emotion,feeding,circadian rhythm,temperature and neuroendocrine.%目的 推测新鉴定的神经肽S (NPS)经其受体激活下丘脑神经元参与下丘脑生理调节,运用神经功能活动形态定位法确定NPS在下丘脑靶神经元的分布.方法 注射NPS(1 nmol,n=6)和生理盐水(n=6),c-fos免疫组化学分别标记大鼠中枢fos免疫反应神经元在下丘脑的分布,并统计分析fos免疫反应神经元数量在各核的变化.结果 与生理盐水比较,NPS增加fos免疫反应神经元,数量分别为下丘脑视交叉上核322%,室旁核108%,背内侧核274%,腹内侧核126%,弓状核267%,穹窿周核520%,结节乳头体腹侧核641%,背侧核586%,外侧区378% (P <0.0001).结论 NPS激活下丘脑上述靶神经元,可能与下丘脑睡眠觉醒周期、

  9. Hypothalamic serotonin-insulin signaling cross-talk and alterations in a type 2 diabetic model.

    Science.gov (United States)

    Papazoglou, Ioannis; Berthou, Flavien; Vicaire, Nicolas; Rouch, Claude; Markaki, Eirini M; Bailbe, Danielle; Portha, Bernard; Taouis, Mohammed; Gerozissis, Kyriaki

    2012-03-05

    Serotonin and insulin are key regulators of homeostatic mechanisms in the hypothalamus. However, in type 2 diabetes, the hypothalamic responsiveness to serotonin is not clearly established. We used a diabetic model, the Goto Kakizaki (GK) rats, to explore insulin receptor expression, insulin and serotonin efficiency in the hypothalamus and liver by means of Akt phosphorylation. Insulin or dexfenfluramine (stimulator of serotonin) treatment induced Akt phosphorylation in Wistar rats but not in GK rats that exhibit down-regulated insulin receptor. Studies in a neuroblastoma cell line showed that serotonin-induced Akt phosphorylation is PI3-kinase dependent. Finally, in response to food intake, hypothalamic serotonin release was reduced in GK rats, indicating impaired responsiveness of this neurotransmitter. In conclusion, hypothalamic serotonin as insulin efficiency is impaired in diabetic GK rats. The insulin-serotonin cross-talk and impairment observed is one potential key modification in the brain during the onset of diabetes.

  10. Medical therapy of hypothalamic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Werder, K. von; Mueller, O.A. (Muenchen Univ. (Germany, F.R.). Medizinische Klinik 1)

    1985-01-01

    Hormonal disturbances caused by hypothalamic pathology can be treated effectively by target hormone replacement in the case of failure of glandotropic hormone secretion. Hyposomatotropism in children has to be substituted by parenteral administration of growth hormone. In addition gonadotropins respectively gonadotropin releasing factor have to be given in order to restore fertility in hypothalamic hypogonadism. Posterior pituitary failure can be adequately replaced by administration of analogues of antidiuretic hormone. Hypothalamic pathology causing hypersecretion of anterior pituitary hormones may also be accessable to medical treatment. This pertains particularly to hyperprolactinemia and precocious puberty. However, there is no medical therapy so far for hypothalamic disturbances leading to veterative dysfunction like disturbances of temperature regulation and control of thirst and polyphagia. In this situation symptomatic correction of the abnormality represents the only possibility to keep these patients alive.

  11. Muscarinic Receptors Types 1 and 2 in the Preoptic-Anterior Hypothalamic Areas Regulate Ovulation Unequally in the Rat Oestrous Cycle

    Directory of Open Access Journals (Sweden)

    Yadira L. López-Ramírez

    2017-01-01

    Full Text Available Muscarinic receptors types 1 (m1AChR and 2 (m2AChR in the preoptic and anterior hypothalamus areas (POA-AHA were counted, and the effects of blocking these receptors on spontaneous ovulation were analysed throughout the rat oestrous cycle. Rats in each phase of the oestrous cycle were assigned to the following experiments: (1 an immunohistochemical study of the number of cells expressing m1AChR or m2AChR in the POA-AHA and (2 analysis of the effects of the unilateral blockade of the m1AChR (pirenzepine, PZP or m2AChR (methoctramine, MTC on either side of the POA-AHA on the ovulation rate. The number of m2AChR-immunoreactive cells was significantly higher at 09:00 h on each day of the oestrous cycle in the POA-AHA region, while no changes in the expression profile of m1AChR protein were observed. The ovulation rate in rats treated with PZP on the oestrous day was lower than that in the vehicle group. Animals treated on dioestrous-1 with PZP or MTC had a higher ovulation rate than those in the vehicle group. In contrast, on dioestrous-2, the MTC treatment decreased the ovulation rate. These results suggest that m1AChR or m2AChR in the POA-AHA could participate in the regulation of spontaneous ovulation in rats.

  12. The effects of three types of stress on fos expression in the hypothalamic paraventricular nucleus, hippocampus and amygdala in female rats at different stages of pregnancy

    OpenAIRE

    Tanaka, Masuo; Hayashi, Shunsuke; Fujioka, Takashi; Tobe, Ikuyo; Nakamura, Shoji

    2011-01-01

    Using immunohistochemistry to reveal the Fos protein (a marker of neuronal activation), the present experiments examined whether there were differences in the responses of the paraventricular nucleus (PVN), hippocampus, and amygdala of pregnant rats exposed to three types of stressors (restraint, immobilization, and communication-box stress), all having inherently different severities, at three pregnancy stages (6 days into pregnancy, or P6, early-pregnancy), P12 (mid-pregnancy) and P18 (late...

  13. Direct evidence for the co-expression of URP and GnRH in a sub-population of rat hypothalamic neurones: anatomical and functional correlation.

    Directory of Open Access Journals (Sweden)

    Johann-Günther Egginger

    Full Text Available Urotensin-II-related peptide (URP is an eight amino-acid neuropeptide recently isolated from rat brain and considered as the endogenous ligand for the GPR14 receptor. Using single and double immunohistochemical labelling, in situ hybridization and ultrastructural immunocytochemistry, we explored the cellular and subcellular localization of URP in the male rat brain. URP peptide was detected in numerous varicose fibres of the median eminence (ME and organum vasculosum laminae terminalis (OVLT as well as in neuronal cell bodies of the medial septal nucleus and diagonal band of Broca where corresponding mRNA were also detected. Combining in situ hybridization with immunohistochemistry, we showed that cell bodies of the rat anterior hypothalamus contained both URP mRNA and GnRH peptide. In addition, double ultrastructural immunodetection of URP and GnRH peptides clearly revealed, in the median eminence, the co-localization of both peptides in the same neuronal processes in the vicinity of fenestrated portal vessels. This remarkable cellular and subcellular distribution led us to test the effect of URP on the GnRH-induced gonadotrophins release in the anterior pituitary, and to discuss its putative role at the level of the median eminence.

  14. Beacon-like/ubiquitin-5-like immunoreactivity is highly expressed in human hypothalamus and increased in haloperidol-treated schizophrenics and a rat model of schizophrenia.

    Science.gov (United States)

    Bernstein, Hans-Gert; Lendeckel, Uwe; Dobrowolny, Henrik; Stauch, Renate; Steiner, Johann; Grecksch, Gisela; Becker, Axel; Jirikowski, Gustav F; Bogerts, Bernhard

    2008-04-01

    The beacon gene is involved in the regulation of energy metabolism, food intake, and obesity. We localized its gene product, beacon-/ubiquitin 5-like immunoreactivity in brains of normal-weight, non-psychotic individuals, adipose (BMI over 32), non-psychotic individuals, and haloperidol-treated schizophrenics. The protein was found to be highly expressed in many neurons of the paraventricular and supraoptic hypothalamic nuclei. Besides, it was detected in neurons of other hypothalamic areas (suprachiasmatic, arcuate, and ventromedial nuclei) as well as outside the hypothalamus (Nuc. basalis Meynert, thalamus, hippocampus, and some neocortical areas). A morphometric analysis of beacon-immunoreactive hypothalamic and neocortical neurons revealed that compared to normal-weight controls in haloperidol-treated schizophrenics, there was a significant increase of protein-expressing supraoptic, paraventricular, and orbitofrontal neurons. However, a significant increase in beacon-expressing supraoptic neurons was also seen in adipose, non-psychotic individuals in comparison with normal-weight controls. Haloperidol at different doses has no effect on beacon expression in SHSY5Y neuroblastoma cells, which makes the assumption unlikely that haloperidol per se is responsible for the increased neuronal expression of the peptide in schizophrenics. In rats with a neonatal lesion of the ventral hippocampus (a widely used animal model of schizophrenia), we found an increased neuronal expression of beacon in the paraventricular and supraoptic nuclei. We suppose that elevated hypothalamic expression of beacon-like protein in non-obese schizophrenics is not primarily related to metabolic alterations, but to a certain role in schizophrenia, which is possibly unrelated to aspects of weight gain and obesity. The latter assumption finds some support by data obtained in rats with ventral hippocampus lesion.

  15. Obsessive-compulsive disorder and ventromedial frontal lesions

    DEFF Research Database (Denmark)

    Irle, E; Exner, C; Thielen, K

    1998-01-01

    OBJECTIVE: The authors sought to determine the long-term outcome of subjects with severe and refractory obsessive-compulsive disorder (OCD) who had undergone ventromedial frontal leukotomy during the 1970s. Special emphasis was given to the analysis of specific lesion sites. METHOD: Sixteen OCD...... resonance imaging scans. RESULTS: The leukotomized OCD subjects showed significant improvement of obsessive-compulsive symptoms; subjects with frontostriatal lesions tended to have improved most. The subjects with combined diagnoses of OCD and obsessive personality disorder (N = 3) had improved...... but not obsessive personality disorder. Lesions of the ventral striatum were significantly related to the occurrence of substance dependence, suggesting a role of this area in human addictive behavior....

  16. Sleep deprivation alters valuation signals in the ventromedial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Camilo eLibedinsky

    2011-10-01

    Full Text Available Even a single night of total sleep-deprivation (SD can have dramatic effects on economic decision making. Here we tested the novel hypothesis that SD influences economic decisions by altering the valuation process. Using functional magnetic resonance imaging (fMRI we identified value signals related to the anticipation and the experience of monetary and social rewards (attractive female faces. We then derived decision value signals that were predictive of each participant’s willingness to exchange money for brief views of attractive faces in an independent market task. Strikingly, SD altered decision value signals in ventromedial prefrontal cortex (VMPFC in proportion to the corresponding change in economic preferences. These changes in preference were independent of the effects of SD on attention and vigilance. Our results provide novel evidence that signals in VMPFC track the current state of the individual, and thus reflect not static but constructed preferences.

  17. Damage to ventromedial prefrontal cortex impairs judgment of harmful intent

    Science.gov (United States)

    Young, Liane; Bechara, Antoine; Tranel, Daniel; Damasio, Hanna; Hauser, Marc; Damasio, Antonio

    2011-01-01

    Summary Moral judgments, whether delivered in ordinary experience or in the courtroom, depend on our ability to infer intentions. We forgive unintentional or accidental harms and condemn failed attempts to harm. Prior work demonstrates that patients with damage to the ventromedial prefrontal cortex (VMPC) deliver abnormal judgments in response to moral dilemmas, and that these patients are especially impaired in triggering emotional responses to inferred or abstract events (e.g., intentions), as opposed to real or actual outcomes. We therefore predicted that VMPC patients would deliver abnormal moral judgments of harmful intentions in the absence of harmful outcomes, as in failed attempts to harm. This prediction was confirmed in the current study: VMPC patients judged attempted harms including attempted murder as more morally permissible relative to controls. These results highlight the critical role of the VMPC in processing harmful intent for moral judgment. PMID:20346759

  18. Behavioral effects of congenital ventromedial prefrontal cortex malformation

    Directory of Open Access Journals (Sweden)

    Boes Aaron D

    2011-12-01

    Full Text Available Abstract Background A detailed behavioral profile associated with focal congenital malformation of the ventromedial prefrontal cortex (vmPFC has not been reported previously. Here we describe a 14 year-old boy, B.W., with neurological and psychiatric sequelae stemming from focal cortical malformation of the left vmPFC. Case Presentation B.W.'s behavior has been characterized through extensive review Patience of clinical and personal records along with behavioral and neuropsychological testing. A central feature of the behavioral profile is severe antisocial behavior. He is aggressive, manipulative, and callous; features consistent with psychopathy. Other problems include: egocentricity, impulsivity, hyperactivity, lack of empathy, lack of respect for authority, impaired moral judgment, an inability to plan ahead, and poor frustration tolerance. Conclusions The vmPFC has a profound contribution to the development of human prosocial behavior. B.W. demonstrates how a congenital lesion to this cortical region severely disrupts this process.

  19. [Functional hypothalamic amenorrhea].

    Science.gov (United States)

    Stárka, Luboslav; Dušková, Michaela

    2015-10-01

    Functional hypothalamic amenorrhea (FHA) besides pregnancy and syndrome of polycystic ovary is one of the most common causes of secondary amenorrhea. FHA results from the aberrations in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which in turn causes impairment of the gonadotropins (follicle-stimulating hormone and luteinizing hormone). FHA is a form of the defence of organism in situations where life functions are more important than reproductive function. FHA is reversible; it can be normalized after ceasing the stress situation. There are three types of FHA: weight loss related, stress-related, and exercise-related amenorrhea. The final consequences are complex hormonal changes manifested by profound hypoestrogenism. Additionally, these patients present mild hypercortisolemia, low serum insulin levels, low insulin-like growth factor 1 (IGF-1) and low total triiodothyronine. Women health in this disorder is disturbed in several aspects including the skeletal system, cardiovascular system, and mental problems. Patients manifest a decrease in bone mass density, which is related to an increase in fracture risk. Therefore, osteopenia and osteoporosis are the main long-term complications of FHA. Cardiovascular complications include endothelial dysfunction and abnormal changes in the lipid profile. FHA patients present significantly higher depression and anxiety and also sexual problems compared to healthy subjects.

  20. [Hypothalamic dysfunction in obesity].

    Science.gov (United States)

    van de Sande-Lee, Simone; Velloso, Licio A

    2012-08-01

    Obesity, defined as abnormal or excessive fat accumulation that may impair life quality, is one of the major public health problems worldwide. It results from an imbalance between food intake and energy expenditure. The control of energy balance in animals and humans is performed by the central nervous system (CNS) by means of neuroendocrine connections, in which circulating peripheral hormones, such as leptin and insulin, provide signals to specialized neurons of the hypothalamus reflecting body fat stores, and induce appropriate responses to maintain the stability of these stores. The majority of obesity cases are associated with central resistance to both leptin and insulin actions. In experimental animals, high-fat diets can induce an inflammatory process in the hypothalamus, which impairs leptin and insulin intracellular signaling pathways, and results in hyperphagia, decreased energy expenditure and, ultimately, obesity. Recent evidence obtained from neuroimaging studies and assessment of inflammatory markers in the cerebrospinal fluid of obese subjects suggests that similar alterations may be also present in humans. In this review, we briefly present the mechanisms involved with the loss of homeostatic control of energy balance in animal models of obesity, and the current evidence of hypothalamic dysfunction in obese humans.

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

    Science.gov (United States)

    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.

  2. Identification of an endocannabinoid system in the rat pars tuberalis-a possible interface in the hypothalamic-pituitary-adrenal system?

    Science.gov (United States)

    Jafarpour, Arsalan; Dehghani, Faramarz; Korf, Horst-Werner

    2017-04-01

    Endocannabinoids (ECs) are ubiquitous endogenous lipid derivatives and play an important role in intercellular communication either in an autocrine/paracrine or in an endocrine fashion. Recently, an intrinsic EC system has been discovered in the hypophysial pars tuberalis (PT) of hamsters and humans. In hamsters, this EC system is under photoperiodic control and appears to influence the secretion of hormones such as prolactin from the adenohypophysis. We investigate the EC system in the PT of the rat, a frequently used species in endocrine research. By means of immunocytochemistry, enzymes involved in EC biosynthesis, e.g., N-arachidonoyl-phosphatidylethanolamine-phospholipase D (NAPE-PLD) and diacylglycerol lipase α (DAGLα) and enzymes involved in EC degradation, e.g., fatty acid amide hydrolase (FAAH) and cyclooxygenase-2 (COX-2), were demonstrated in PT cells of the rat. Immunoreactions (IR) for FAAH and for the cannabinoid receptor CB1 were observed in corticotrope cells of the rat adenohypophysis; these cells were identified by antibodies against proopiomelanocortin (POMC) or adrenocorticotrophic hormone (ACTH). In the outer zone of the median eminence, numerous nerve fibers and terminals displayed CB1 IR. The majority of these were also immunolabeled by an antibody against corticotropin-releasing factor (CRF). These results suggest that the EC system at the hypothalamo-hypophysial interface affects both the CRF-containing nerve fibers and the corticotrope cells in the adenohypophysis. Our data give rise to the hypothesis that, in addition to its well-known role in the reproductive axis, the PT might influence adrenal functions and, thus, the stress response and immune system.

  3. 损毁炎症大鼠下丘脑弓状核对痛觉过敏的影响%The effect of hypothalamic arcuate nucleus lesion on the hyperalgesia of inflammatory rats

    Institute of Scientific and Technical Information of China (English)

    戴友爱; 龚珊; 蒋星红

    2012-01-01

    目的 观察损毁炎症大鼠下丘脑弓状核( ARC)对炎症大鼠痛觉过敏的影响.方法 用完全弗氏佐剂(CFA)建立大鼠外周组织炎症模型;采用新生期大鼠注射谷氨酸单钠(MSG)破坏ARC神经元或电解损毁成年大鼠的ARC;用辐射热-缩腿法测定炎症大鼠热痛阈的变化,用von Frey法测定机械痛阈的变化.结果 (1)大鼠在注射CFA后热痛阈和机械痛阈均明显降低,出现痛觉过敏,3h达到高峰,到第3天有所恢复并且稳定维持痛觉过敏状态,一直维持到本实验观察的第14天;(2)新生期注射MSG的大鼠在注射CFA后3h,热痛阈和机械痛阈也明显降低,出现痛觉过敏,但其痛阈降低的幅度明显小于注射高渗盐水对照的CFA组;(3)CFA炎症大鼠在电解损毁ARC之后,其热痛阈和机械痛阈与假损毁组相比,均明显上升,即痛觉过敏减轻.结论 在外周存在炎症条件下,两种方法损毁ARC都能减轻痛觉过敏.提示ARC参与外周组织炎症引起的痛觉过敏,对痛觉过敏的发生有下行易化作用.%Objective To study the effect of hypothalamic arcuate nucleus ( ARC) lesion on the hyperalgesia of inflammatory rats and investigate the descending modulation on hyperalgesia from ARC. Methods The peripheral inflammation model was established by sub-plantar injection of complete Freund' s adjuvant ( CFA) in rats. ARC was lesioned electrolytically and by neonatal injection of monosodium glutamate ( MSG). The thermal pain threshold was measured by radiant heat-withdrawal method and the mechanical pain threshold was measured by von Frey method. Results ( 1 ) Hyperalgesia ( decrease of thermal and mechanical pain threshold) appeared after injection of CFA, the peak time was at 3h, and the hyperalgesic state could last for 14 days (2) In MSG-treated neonatal rats the thermal and mechanical pain threshold were decreased at 3h after CFA injection, but the amplitude of decrement was significantly less as compared with

  4. Ghrelin modulates the fMRI BOLD response of homeostatic and hedonic brain centers regulating energy balance in the rat.

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    Miklós Sárvári

    Full Text Available The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin's BOLD effect in a region specific manner. In females, the

  5. Androgen receptors and estrogen receptors are colocalized in male rat hypothalamic and limbic neurons that express Fos immunoreactivity induced by mating.

    Science.gov (United States)

    Gréco, B; Edwards, D A; Michael, R P; Clancy, A N

    1998-01-01

    Conversion of testosterone into estradiol is important for male rat sexual behavior, and both steroids probably contribute to mating. The distributions of neurons containing androgen receptors (AR) and estrogen receptors (ER) overlap, and many AR-immunoreactive (AR-ir) neurons express Fos immunoreactivity (Fos-ir) induced by mating. Because mating-induced Fos-ir in the male rat occurs mainly in AR-ir neurons, and because both steroids are important for mating, we hypothesized that (i) AR-ir and ER-ir are colocalized and that (ii) some of these neurons are activated during mating. We examined, in adjacent sections from the medial preoptic area (MPN) through the central tegmental field (CTF), the expression of ER-ir in: (i) AR-ir-containing neurons, and (ii) Fos-ir-expressive neurons. PG21 anti-AR, OA-11-824 anti-c-fos, H222 or 1D5 anti-ER primary antibodies were visualized, respectively, with cyanine-conjugated, fluorescein- or cyanine-conjugated, and fluorescein-conjugated secondary antibodies in male rats which were killed 1 h after ejaculating with a receptive female. In MPN, bed nucleus of the stria terminalis (BNST), and medial amygdala (MEA), 80-90% of ER-ir labeling occurred in AR-ir-positive neurons but only about 30% of AR-ir neurons were ER-ir-positive. No ER-ir was found in the CTF. This suggests the presence of three types of brain neurons sensitive to gonadal steroid hormones: neurons sensitive to androgens only, neurons sensitive to both androgens and estrogens, and neurons sensitive to estrogens only. About 50% of ER-ir labeling occurred in cells expressing mating-induced Fos-ir but only about 30% of Fos-ir neurons were ER-ir-positive. These findings suggest that, in the MPN, at least two different neuronal populations are activated during mating: the first contains AR-ir only and the second contains AR-ir and ER-ir. In the BNST and MEA, at least three hormonally sensitive populations are activated during mating: the two described above plus a third

  6. Neuropeptide Y in the arcuato-paraventricular pathway and diet selection in the vasopressin-deficient Brattleboro rat.

    Science.gov (United States)

    Beck, Bernard; Max, Jean-Pierre

    2008-07-01

    Neuropeptide Y (NPY) is one of the most important brain peptides involved in feeding behavior. It influences both food choice and fluid homeostasis. The paraventricular and arcuate nuclei belong to the main pathway through which NPY stimulates carbohydrate intake. In this study, we measured NPY in various hypothalamic microdissected areas in Brattleboro di/di rats, a rat model of diabetes insipidus with specific dietary preferences. We confirmed that this rat is characterized by an increased fat intake (+10%; p<0.001) and a decreased carbohydrate intake (-10%; p<0.001) leading to a completely different dietary profile than that of di/+ controls. This profile was associated with a decrease in NPY in the paraventricular nucleus (-33%; p<0.005) and in the ventromedial nucleus (-24%; p<0.002). Intake of carbohydrate was negatively correlated with the gradient of NPY concentration between the arcuate and paraventricular nuclei. NPY could therefore contribute to the qualitative changes of feeding behavior in the Brattleboro rat through altered transport/release of the peptide and participate in the balance of neuropeptides that determines food choice in this strain of rat.

  7. Exercise training does not enhance hypothalamic responsiveness to leptin or ghrelin in male mice.

    Science.gov (United States)

    Borg, M L; Andrews, Z B; Watt, M J

    2014-02-01

    The detection of hormone and nutrient signals by the hypothalamus is blunted in obesity and contributes to dysregulated energy homeostasis. We investigated whether aerobic exercise training would improve long-term hypothalamic sensitivity to both leptin and ghrelin, independent of acute exercise-induced signalling. Male C57Bl/6J mice were fed either a chow or high-fat diet for 6 weeks, then remained sedentary on their respective diet, or completed 6 weeks of treadmill exercise training with a progressive increase in exercise volume and intensity. Food intake and hypothalamic signalling were assessed in mice injected with leptin or ghrelin at least 24 h after the last exercise bout. Exercise training reduced body mass, increased daily food intake and improved glucose tolerance. Intraperitoneal leptin administration reduced food intake in lean and obese mice, and this was not enhanced after exercise training. Leptin-mediated activation of phosphorylated signal transducer and activator of transcription 3 in the arcuate nucleus and ventromedial nucleus of the hypothalamus was not enhanced with exercise training. Ghrelin increased food intake and c-Fos positive neurones in the hypothalamus in lean and obese mice, and these physiological and molecular responses were not enhanced with exercise training. This suggests that the previously reported exercise effects on sensitising hypothalamic signalling and food intake responses may be limited to the period immediately after an exercise bout, and are not a result of stable structural or molecular changes that occur with exercise training. © 2014 British Society for Neuroendocrinology.

  8. Differential sensitivity to nicotine among hypothalamic magnocellular neurons

    DEFF Research Database (Denmark)

    Mikkelsen, J D; Jacobsen, Julie; Kiss, Adrian Emil

    2012-01-01

    The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated...... is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin....

  9. Differential sensitivity to nicotine among hypothalamic magnocellular neurons

    DEFF Research Database (Denmark)

    Mikkelsen, J D; Jacobsen, Julie; Kiss, Adrian Emil

    2012-01-01

    The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated...... is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin....

  10. Proliferative hypothalamic neurospheres express NPY, AGRP, POMC, CART and Orexin-A and differentiate to functional neurons.

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    Lígia Sousa-Ferreira

    Full Text Available Some pathological conditions with feeding pattern alterations, including obesity and Huntington disease (HD are associated with hypothalamic dysfunction and neuronal cell death. Additionally, the hypothalamus is a neurogenic region with the constitutive capacity to generate new cells of neuronal lineage, in adult rodents. The aim of the present work was to evaluate the expression of feeding-related neuropeptides in hypothalamic progenitor cells and their capacity to differentiate to functional neurons which have been described to be affected by hypothalamic dysfunction. Our study shows that hypothalamic progenitor cells from rat embryos grow as floating neurospheres and express the feeding-related neuropeptides Neuropeptide Y (NPY, Agouti-related Protein (AGRP, Pro-OpioMelanocortin (POMC, Cocaine-and-Amphetamine Responsive Transcript (CART and Orexin-A/Hypocretin-1. Moreover the relative mRNA expression of NPY and POMC increases during the expansion of hypothalamic neurospheres in proliferative conditions.Mature neurons were obtained from the differentiation of hypothalamic progenitor cells including NPY, AGRP, POMC, CART and Orexin-A positive neurons. Furthermore the relative mRNA expression of NPY, CART and Orexin-A increases after the differentiation of hypothalamic neurospheres. Similarly to the adult hypothalamic neurons the neurospheres-derived neurons express the glutamate transporter EAAT3. The orexigenic and anorexigenic phenotype of these neurons was identified by functional response to ghrelin and leptin hormones, respectively. This work demonstrates the presence of appetite-related neuropeptides in hypothalamic progenitor cells and neurons obtained from the differentiation of hypothalamic neurospheres, including the neuronal phenotypes that have been described by others as being affected by hypothalamic neurodegeneration. These in vitro models can be used to study hypothalamic progenitor cells aiming a therapeutic intervention to

  11. Gelastic epilepsy: Beyond hypothalamic hamartomas

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    Reinaldo Uribe-San-Martin

    2015-01-01

    Full Text Available Gelastic epilepsy or laughing seizures have been historically related to children with hypothalamic hamartomas. We report three adult patients who had gelastic epilepsy, defined as the presence of seizures with a prominent laugh component, including brain imaging, surface/invasive electroencephalography, positron emission tomography, and medical/surgical outcomes. None of the patients had hamartoma or other hypothalamic lesion. Two patients were classified as having refractory epilepsy (one had biopsy-proven neurocysticercosis and the other one hippocampal sclerosis and temporal cortical dysplasia. The third patient had no lesion on MRI and had complete control with carbamazepine. Both lesional patients underwent resective surgery, one with complete seizure control and the other one with poor outcome. Although hypothalamic hamartomas should always be ruled out in patients with gelastic epilepsy, laughing seizures can also arise from frontal and temporal lobe foci, which can be surgically removed. In addition, we present the first case of gelastic epilepsy due to neurocysticercosis.

  12. GIT2 acts as a potential keystone protein in functional hypothalamic networks associated with age-related phenotypic changes in rats.

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    Wayne Chadwick

    Full Text Available The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities. The maintenance of good health during the aging process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats. Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process.

  13. Long-term gene therapy in the CNS: reversal of hypothalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin.

    Science.gov (United States)

    Geddes, B J; Harding, T C; Lightman, S L; Uney, J B

    1997-12-01

    The ability of adenovirus (Ad) to transfect most cell types efficiently has already resulted in human gene therapy trials involving the systemic administration of adenoviral constructs. However, because of the complexity of brain function and the difficulty in noninvasively monitoring alterations in neuronal gene expression, the potential of Ad gene therapy strategies for treating disorders of the CNS has been difficult to assess. In the present study, we have used an Ad encoding the arginine vasopressin cDNA (AdAVP) in an AVP-deficient animal model of diabetes insipidus (the Brattleboro rat), which allowed us to monitor chronically the success of the gene therapy treatment by noninvasive assays. Injection of AdAVP into the supraoptic nuclei (SON) of the hypothalamus resulted in expression of AVP in magnocellular neurons. This was accompanied by reduced daily water intake and urine volume, as well as increased urine osmolality lasting 4 months. These data show that a single gene defect leading to a neurological disorder can be corrected with an adenovirus-based strategy. This study highlights the potential of using Ad gene therapy for the long-term treatment of disorders of the CNS.

  14. Mechanisms of the regional hemodynamic effects of a mu-opioid receptor agonist microinjected into the hypothalamic paraventricular nuclei of conscious unrestrained rats.

    Science.gov (United States)

    Bachelard, H; Pître, M; Lessard, A

    1997-01-01

    The present study was undertaken to characterize the mechanisms of the hemodynamic responses to microinjection of the selective mu-opioid receptor agonist [D-Ala2,MePhe4,Gly5-ol]enkephalin (DAMGO) into the paraventricular nucleus of the hypothalamus, in conscious rats chronically instrumented with pulsed Doppler flow probes. We found that i.v. pretreatment with phentolamine had no effect on the tachycardia elicited by DAMGO (1 nmol); however, the pressor response was reversed to a state of hypotension, the renal and superior mesenteric vasoconstrictions were attenuated and the hindquarter vasodilation was potentiated. In the presence of propranolol, the pressor response and renal vasoconstriction were unchanged, whereas the superior mesenteric vasoconstriction was reduced and the hindquarter vasodilation was abolished. Moreover, in those animals we observed bradycardia followed by tachycardia. Combined i.v. pretreatment with phentolamine and propranolol abolished the pressor and heart rate responses to DAMGO but had no effect on the renal and superior mesenteric vasoconstrictions, although the hindquarter vasodilation was reduced. Intravenous pretreatment with a vasopressin V1 receptor antagonist or captopril had no effect on the cardiovascular responses to DAMGO. Together, these results indicate that the hypertension observed after injection of DAMGO into the paraventricular nucleus of the hypothalamus was secondary to alpha adrenoceptor-mediated vasoconstrictions in renal and superior mesenteric vascular beds and to beta adrenoceptor-mediated vasodilation in the hindquarter vascular bed, whereas the involvement of circulating vasopressin or angiotensin seems less obvious from the present findings. However, we cannot exclude the possibility that nonadrenergic, nonvasopressinergic and nonangiotensinergic vasoconstrictor mechanisms were acting in the renal and superior mesenteric vascular beds.

  15. Susceptibility to social pressure following ventromedial prefrontal cortex damage.

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    Chen, Kuan-Hua; Rusch, Michelle L; Dawson, Jeffrey D; Rizzo, Matthew; Anderson, Steven W

    2015-11-01

    Social pressure influences human behavior including risk taking, but the psychological and neural underpinnings of this process are not well understood. We used the human lesion method to probe the role of ventromedial prefrontal cortex (vmPFC) in resisting adverse social pressure in the presence of risk. Thirty-seven participants (11 with vmPFC damage, 12 with brain damage outside the vmPFC and 14 without brain damage) were tested in driving simulator scenarios requiring left-turn decisions across oncoming traffic with varying time gaps between the oncoming vehicles. Social pressure was applied by a virtual driver who honked aggressively from behind. Participants with vmPFC damage were more likely to select smaller and potentially unsafe gaps under social pressure, while gap selection by the comparison groups did not change under social pressure. Participants with vmPFC damage also showed prolonged elevated skin conductance responses (SCR) under social pressure. Comparison groups showed similar initial elevated SCR, which then declined prior to making left-turn decisions. The findings suggest that the vmPFC plays an important role in resisting explicit and immediately present social pressure with potentially negative consequences. The vmPFC appears to contribute to the regulation of emotional responses and the modulation of decision making to optimize long-term outcomes.

  16. CB1 cannabinoid receptor-mediated anandamide signalling reduces the defensive behaviour evoked through GABAA receptor blockade in the dorsomedial division of the ventromedial hypothalamus.

    Science.gov (United States)

    Dos Anjos-Garcia, Tayllon; Ullah, Farhad; Falconi-Sobrinho, Luiz Luciano; Coimbra, Norberto Cysne

    2017-02-01

    The effects of cannabinoids in brain areas expressing cannabinoid receptors, such as hypothalamic nuclei, are not yet well known. Several studies have demonstrated the role of hypothalamic nuclei in the organisation of behavioural responses induced through innate fear and panic attacks. Panic-prone states are experimentally induced in laboratory animals through a reduction in the GABAergic activity. The aim of the present study was to examine panic-like elaborated defensive behaviour evoked by GABAA receptor blockade with bicuculline (BIC) in the dorsomedial division of the ventromedial hypothalamus (VMHdm). We also aimed to characterise the involvement of endocannabinoids and the CB1 cannabinoid receptor in the modulation of elaborated defence behavioural responses organised with the VMHdm. The guide-cannula was stereotaxicaly implanted in VMHdm and the animals were treated with anandamide (AEA) at different doses, and the effective dose was used after the pre-treatment with the CB1 receptor antagonist AM251, followed by GABAA receptor blockade in VMHdm. The results showed that the intra-hypothalamic administration of AEA at an intermediate dose (5 pmol) attenuated defence responses induced through the intra-VMHdm microinjection of bicuculline (40 ng). This effect, however, was inhibited when applied central microinjection of the CB1 receptor antagonist AM251 in the VMHdm. Moreover, AM251 potentiates de non-oriented escape induced by bicuculline, effect blocked by pre-treatment with the TRPV1 channel antagonist 6-I-CPS. These results indicate that AEA modulates the pro-aversive effects of intra-VMHdm-bicuculline treatment, recruiting CB1 cannabinoid receptors and the TRPV1 channel is involved in the AM251-related potentiation of bicuculline effects on non-oriented escape behaviour.

  17. Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP

    Science.gov (United States)

    Imbernon, Monica; Sanchez-Rebordelo, Estrella; Gallego, Rosalia; Gandara, Marina; Lear, Pamela; Lopez, Miguel; Dieguez, Carlos; Nogueiras, Ruben

    2014-01-01

    Krüppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed in a range of tissues that plays multiple functions. We report that hypothalamic KLF4 represents a new transcription factor specifically modulating agouti-related protein (AgRP) expression in vivo. Hypothalamic KLF4 colocalizes with AgRP neurons and is modulated by nutritional status and leptin. Over-expression of KLF4 in the hypothalamic arcuate nucleus (ARC) induces food intake and increases body weight through the specific stimulation of AgRP, as well as blunting leptin sensitivity in lean rats independent of forkhead box protein 01 (FoxO1). Down-regulation of KLF4 in the ARC inhibits fasting-induced food intake in both lean and diet-induced obese (DIO) rats. Silencing KLF4, however, does not, on its own, enhance peripheral leptin sensitivity in DIO rats. PMID:24944903

  18. Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP.

    Science.gov (United States)

    Imbernon, Monica; Sanchez-Rebordelo, Estrella; Gallego, Rosalia; Gandara, Marina; Lear, Pamela; Lopez, Miguel; Dieguez, Carlos; Nogueiras, Ruben

    2014-07-01

    Krüppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed in a range of tissues that plays multiple functions. We report that hypothalamic KLF4 represents a new transcription factor specifically modulating agouti-related protein (AgRP) expression in vivo. Hypothalamic KLF4 colocalizes with AgRP neurons and is modulated by nutritional status and leptin. Over-expression of KLF4 in the hypothalamic arcuate nucleus (ARC) induces food intake and increases body weight through the specific stimulation of AgRP, as well as blunting leptin sensitivity in lean rats independent of forkhead box protein 01 (FoxO1). Down-regulation of KLF4 in the ARC inhibits fasting-induced food intake in both lean and diet-induced obese (DIO) rats. Silencing KLF4, however, does not, on its own, enhance peripheral leptin sensitivity in DIO rats.

  19. Social crowding stress diminishes the pituitary-adrenocortical and hypothalamic histamine response to adrenergic stimulation.

    Science.gov (United States)

    Bugajski, J; Gadek-Michalska, A; Borycz, J

    1993-12-01

    Social stress of crowding almost totally reduced the rise in serum corticosterone elicited by intracerebroventricular administration of isoprenaline, a beta-adrenergic receptor agonist, after 3 and 7 day of crowding and substantially diminished that response after 14 and 21 days. Crowding stress totally abolished the increase in hypothalamic histamine induced by isoprenaline in control rats. Crowding also significantly diminished the increase in serum corticosterone evoked by clonidine, an alpha 2-adrenergic agonist, and abolished the clonidine-induced elevation in hypothalamic histamine levels. The stimulatory effect of phenylephrine, an alpha 1-adrenergic agonist, on corticosterone secretion was only moderately diminished in crowded rats. Neither phenylephrine nor crowding stress changed significantly the hypothalamic histamine levels. These results indicate that social stress of crowding considerably impairs the hypothalamic-pituitary-adrenocortical responsiveness to central beta- and alpha 2-adrenergic receptor stimulation. Crowding also abolishes the rise in hypothalamic histamine induced by beta- and alpha 2-adrenergic agonist, suggesting a role of hypothalamic histamine in the HPA adaptation to the social stress of crowding.

  20. Schema representation in patients with ventromedial PFC lesions.

    Science.gov (United States)

    Ghosh, Vanessa E; Moscovitch, Morris; Melo Colella, Brenda; Gilboa, Asaf

    2014-09-01

    Human neuroimaging and animal studies have recently implicated the ventromedial prefrontal cortex (vmPFC) in memory schema, particularly in facilitating new encoding by existing schemas. In humans, the most conspicuous memory disorder following vmPFC damage is confabulation; strategic retrieval models suggest that aberrant schema activation or reinstatement plays a role in confabulation. This raises the possibility that beyond its role in schema-supported memory encoding, the vmPFC is also implicated in schema reinstatement itself. If that is the case, vmPFC lesions should lead to impaired schema-based operations, even on tasks that do not involve memory acquisition. To test this prediction, ten patients with vmPFC damage, four with present or prior confabulation, and a group of twelve matched healthy controls made speeded yes/no decisions as to whether words were closely related to a schema (a visit to the doctor). Ten minutes later, they repeated the task for a new schema (going to bed) with some words related to the first schema included as lures. Last, they rated the degree to which stimuli were related to the second schema. All four vmPFC patients with present or prior confabulation were impaired in rejecting lures and in classifying stimulus belongingness to the schema, even when they were not lures. Nonconfabulating patients performed comparably to healthy adults with high accuracy, comparable reaction times, and similar ratings. These results show for the first time that damage to the human vmPFC, when associated with confabulation, leads to deficient schema reinstatement, which is likely a prerequisite for schema-mediated memory integration.

  1. Alterations in hypothalamic gene expression following Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Barkholt, Pernille; Pedersen, Philip J.; Hay-Schmidt, Anders

    2016-01-01

    of energy balance.  Methods: Lean male Sprague-Dawley rats underwent either RYGB or sham surgery. Body weight and food intake were monitored bi-weekly for 60 days post-surgery. In situ hybridization mRNA analysis of hypothalamic AgRP, NPY, CART, POMC and MCH was applied to RYGB and sham animals and compared......Objective: The role of the central nervous system in mediating metabolic effects of Roux-en-Y gastric bypass (RYGB) surgery is poorly understood. Using a rat model of RYGB, we aimed to identify changes in gene expression of key hypothalamic neuropeptides known to be involved in the regulation...

  2. Activation of rostral ventromedial medulla neurons by noxious stimulation of cutaneous and deep craniofacial tissues.

    Science.gov (United States)

    Khasabov, Sergey G; Malecha, Patrick; Noack, Joseph; Tabakov, Janneta; Okamoto, Keiichiro; Bereiter, David A; Simone, Donald A

    2015-01-01

    The rostral ventromedial medulla (RVM) projects to the medullary and spinal dorsal horns and is a major source of descending modulation of nociceptive transmission. Traditionally, neurons in the RVM are classified functionally as on, off, and neutral cells on the basis of responses to noxious cutaneous stimulation of the tail or hind paw. On cells facilitate nociceptive transmission, off cells are inhibitory, whereas neutral cells are unresponsive to noxious stimuli and their role in pain modulation is unclear. Classification of RVM neurons with respect to stimulation of craniofacial tissues is not well defined. In isoflurane-anesthetized male rats, RVM neurons first were classified as on (25.5%), off (25.5%), or neutral (49%) cells by noxious pinch applied to the hind paw. Pinching the skin overlying the temporomandibular joint (TMJ) altered the proportions of on (39.2%), off (42.2%), and neutral (19.6%) cells. To assess the response of RVM cells to specialized craniofacial inputs, adenosine triphosphate (ATP; 0.01-1 mM) was injected into the TMJ and capsaicin (0.1%) was applied to the ocular surface. TMJ and ocular surface stimulation also resulted in a reduced proportion of neutral cells compared with hind paw pinch. Dose-effect analyses revealed that on and off cells encoded the intra-TMJ concentration of ATP. These results suggest that somatotopy plays a significant role in the functional classification of RVM cells and support the notion that neutral cells likely are subgroups of on and off cells. It is suggested that a portion of RVM neurons serve different functions in modulating craniofacial and spinal pain conditions.

  3. Trigeminal-Rostral Ventromedial Medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury

    Directory of Open Access Journals (Sweden)

    Chai Bryan

    2012-10-01

    Full Text Available Abstract Background Our previous studies have shown that complete Freund’s adjuvant (CFA-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM, a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results Microinjection of the IL-1 receptor antagonist (5 nmol, n=6 into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol and L-733,060 (0.5-11.4 nmol, attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol, attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

  4. Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat

    DEFF Research Database (Denmark)

    Kiss, Alexander; Søderman, Andreas; Bundzikova, Jana;

    2006-01-01

    Functional activation of oxytocinergic (OXY) cells in the hypothalamic paraventricular (PVN), supraoptic (SON), and accessory (ACC) nuclei was investigated in response to acute treatment with Zolpidem (a GABA(A) receptor agonist with selectivity for alpha(1) subunits) utilizing dual Fos/OXY immun...

  5. Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat

    DEFF Research Database (Denmark)

    Kiss, Alexander; Søderman, Andreas; Bundzikova, Jana

    2006-01-01

    Functional activation of oxytocinergic (OXY) cells in the hypothalamic paraventricular (PVN), supraoptic (SON), and accessory (ACC) nuclei was investigated in response to acute treatment with Zolpidem (a GABA(A) receptor agonist with selectivity for alpha(1) subunits) utilizing dual Fos/OXY immun...

  6. Anterior hypothalamic knife cut eliminates a specific component of the predatory behavior elicited by electrical stimulation of the posterior hypothalamus or ventral midbrain in the cat.

    Science.gov (United States)

    Halliday, R; Bandler, R

    1981-01-20

    Following unilateral transection of the medial forebrain bundle (MFB) within the anterior hypothalamic-preoptic region of cats, the biting attack upon a rat elicited by ipsilateral posterior hypothalamic or ventral midbrain stimulation is eliminated, although the cat continues to approach from 2.8 metres away to within several centimetres of the rat. In contrast, both the approach to and biting attack upon a rat elicited by contralateral posterior hypothalamic and ventral midbrain stimulation are unchanged. The results suggest that specific agents (biting, approach) of the elicited behaviour may be mediated by neural effects which proceed along anatomically distinct components of the ascending as well as the descending MFB.

  7. HYPOTHALAMIC NEUROHORMONES AND IMMUNE RESPONSES

    Directory of Open Access Journals (Sweden)

    J. Luis eQuintanar

    2013-08-01

    Full Text Available The aim of this review is to provide a comprehensive examination of the current literature describing the neural-immune interactions, with emphasis on the most recent findings of the effects of neurohormones on immune system. Particularly, the role of hypothalamic hormones such as Thyrotropin-releasing hormone, Corticotropin-releasing hormone and Gonadotropin-releasing hormone. In the past few years, interest has been raised in extrapituitary actions of these neurohormones due to their receptors have been found in many non-pituitary tissues. Also, the receptors are present in immune cells, suggesting an autocrine or paracrine role within the immune system. In general, these neurohormones have been reported to exert immunomodulatory effects on cell proliferation, immune mediators release and cell function. The implications of these findings in understanding the network of hypothalamic neuropeptides and immune system are discussed.

  8. Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

    Directory of Open Access Journals (Sweden)

    Alvarez-Bolado Gonzalo

    2012-01-01

    Full Text Available Abstract Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E9.5 contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia. Progenitors labeled at later stages (after E9.5 give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly

  9. Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

    Science.gov (United States)

    2012-01-01

    Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh) is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM) to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E)9.5) contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia). Progenitors labeled at later stages (after E9.5) give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly defined progenitor domains

  10. The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats.

    Science.gov (United States)

    Toorie, Anika M; Cyr, Nicole E; Steger, Jennifer S; Beckman, Ross; Farah, George; Nillni, Eduardo A

    2016-03-11

    Understanding the role of hypothalamic neuropeptides and hormones in energy balance is paramount in the search for approaches to mitigate the obese state. Increased hypothalamic-pituitary-adrenal axis activity leads to increased levels of glucocorticoids (GC) that are known to regulate body weight. The axis initiates the production and release of corticotropin-releasing hormone (CRH) from the paraventricular nucleus (PVN) of the hypothalamus. Levels of active CRH peptide are dependent on the processing of its precursor pro-CRH by the action of two members of the family of prohormone convertases 1 and 2 (PC1 and PC2). Here, we propose that the nutrient sensor sirtuin 1 (Sirt1) regulates the production of CRH post-translationally by affecting PC2. Data suggest that Sirt1 may alter the preproPC2 gene directly or via deacetylation of the transcription factor Forkhead box protein O1 (FoxO1). Data also suggest that Sirt1 may alter PC2 via a post-translational mechanism. Our results show that Sirt1 levels in the PVN increase in rats fed a high fat diet for 12 weeks. Furthermore, elevated Sirt1 increased PC2 levels, which in turn increased the production of active CRH and GC. Collectively, this study provides the first evidence supporting the hypothesis that PVN Sirt1 activates the hypothalamic-pituitary-adrenal axis and basal GC levels by enhancing the production of CRH through an increase in the biosynthesis of PC2, which is essential in the maturation of CRH from its prohormone, pro-CRH.

  11. Expression of the neuronal nitric oxide synthase in the paraventricular hypothalamic nucleus in rats with metabolic syndrome%代谢综合征大鼠下丘脑室旁核神经元型一氧化氮合酶的表达

    Institute of Scientific and Technical Information of China (English)

    马同军; 吴锋

    2012-01-01

    Objective:To examine the changes of neuronal nitric oxide synthase (nNOS) expression in paraventricular hypothalamic nucleus (PVN) in rats with metabolic syndrome, and explore the mechanisms of nitric oxide(NO) in PVN in inducing the metabolic syndrome. Methods : A high-fat,refined-carbohydrate diet was given to the rats for 24 weeks to induce metabolic syndrome. Immunohistostaining was performed to examine the expression of nNOS in PVN. Results: Compared with the normal control group,the expression of nNOS in the model group were up-regulated significantly(P<0.01). Conclusion :The fact that evidently up-regulated nNOS expression in PVN was seen in rats with metabolic syndrome suggest that the changes of nNOS activities may be involved in variation of the cerebral nemo endocrine.%目的:观察代谢综合征大鼠下丘脑室旁核(paraventricular hypothalamic nucleus,PVN)内神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)表达的变化,探讨PVN内一氧化氮(nitric oxide,NO)在代谢综合征发病中的作用机制.方法:高脂高糖诱导大鼠代谢综合征24周,应用免疫组织化学染色方法观察代谢综合征大鼠PVN内nNOS的表达.结果:与对照组相比较,模型组PVN内nNOS表达明显增加(P<0.01).结论:PVN内nNOS的表达在代谢综合征大鼠中明显升高,nNOS活性改变可能与代谢综合征神经内分泌改变有关.

  12. 交泰丸对睡眠剥夺大鼠下丘脑Orexin A及γ-氨基丁酸的影响%Effect of Jiaotai Pills on Hypothalamic Orexin A and Gamma-aminobutyric Acid in Sleep Deprivation Rats

    Institute of Scientific and Technical Information of China (English)

    全世建; 焦蒙蒙; 黑赏艳; 钱莉莉

    2015-01-01

    Objective To observe the effect of Jiaotai Pills ( JP) on hypothalamic neurotransmitters of Orexin A and gamma-aminobutyric acid ( GABA) in rapid eye movement ( REM) sleep deprivation rats. Methods Rat model of REM-sleep deprivation was established by water small platform method. The rats were randomized into 6 groups, namely normal control group, model group, Diazepam group (3 mg/kg), and high-, medium-and low-dose JP groups ( JP in the dosage of 18.6, 9.3 and 4.6 g/kg respectively) . Enzyme-labeled instrument was used to detect the absorbance ratio of rat hypothalamic Orexin A content, and high performance liquid phase electrochemical detection method was adopted for the detection of hypothalamic GABA content. Results Compared with the normal control group, all of the rats in the model group suffered from insomnia, and the Orexin A content was increased ( P0.05) . Conclusion The sedative and hypnic mechanism of JP is probably related with the inhibition of hypothalamic Orexin A.%【目的】观察交泰丸对快速动眼(REM)睡眠剥夺大鼠下丘脑神经递质Orexin A及γ-氨基丁酸(GABA)的影响。【方法】采用水环境小平台法制备大鼠睡眠剥夺模型,将造模成功的大鼠随机分为6组,即交泰丸高、中、低剂量组(剂量分别为18.6、9.3、4.6 g/kg),地西泮组(剂量为3 mg/kg)、模型组及正常组,采用酶标仪吸光度法检测大鼠下丘脑促觉醒神经递质Orexin A,高效液相法库伦电化学检测大鼠下丘脑促睡眠神经递质GABA。【结果】与正常组比较,模型组大鼠完全处于失眠状态,其下丘脑Orexin A含量显著升高( P<0.05);与模型组比较,交泰丸高、中、低剂量组失眠状态有明显改善, Orexin A含量显著降低(P<0.05);与模型组比较,交泰丸高、中、低剂量组GABA含量无显著变化(P>0.05)。【结论】交泰丸的镇静催眠作用可能是通过抑制大鼠下

  13. Sex differences in hypothalamic astrocyte response to estradiol stimulation

    Directory of Open Access Journals (Sweden)

    Kuo John

    2010-11-01

    Full Text Available Abstract Background Reproductive functions controlled by the hypothalamus are highly sexually differentiated. One of the most dramatic differences involves estrogen positive feedback, which leads to ovulation. A crucial feature of this positive feedback is the ability of estradiol to facilitate progesterone synthesis in female hypothalamic astrocytes. Conversely, estradiol fails to elevate hypothalamic progesterone levels in male rodents, which lack the estrogen positive feedback-induced luteinizing hormone (LH surge. To determine whether hypothalamic astrocytes are sexually differentiated, we examined the cellular responses of female and male astrocytes to estradiol stimulation. Methods Primary adult hypothalamic astrocyte cultures were established from wild type rats and mice, estrogen receptor-α knockout (ERKO mice, and four core genotype (FCG mice, with the sex determining region of the Y chromosome (Sry deleted and inserted into an autosome. Astrocytes were analyzed for Sry expression with reverse transcription PCR. Responses to estradiol stimulation were tested by measuring free cytoplasmic calcium concentration ([Ca2+]i with fluo-4 AM, and progesterone synthesis with column chromatography and radioimmunoassay. Membrane estrogen receptor-α (mERα levels were examined using surface biotinylation and western blotting. Results Estradiol stimulated both [Ca2+]i release and progesterone synthesis in hypothalamic astrocytes from adult female mice. Male astrocytes had a significantly elevated [Ca2+]i response but it was significantly lower than in females, and progesterone synthesis was not enhanced. Surface biotinylation demonstrated mERα in both female and male astrocytes, but only in female astrocytes did estradiol treatment increase insertion of the receptor into the membrane, a necessary step for maximal [Ca2+]i release. Regardless of the chromosomal sex, estradiol facilitated progesterone synthesis in astrocytes from mice with ovaries

  14. Effects of sugar solutions on hypothalamic appetite regulation.

    Science.gov (United States)

    Colley, Danielle L; Castonguay, Thomas W

    2015-02-01

    Several hypotheses for the causes of the obesity epidemic in the US have been proposed. One such hypothesis is that dietary intake patterns have significantly shifted to include unprecedented amounts of refined sugar. We set out to determine if different sugars might promote changes in the hypothalamic mechanisms controlling food intake by measuring several hypothalamic peptides subsequent to overnight access to dilute glucose, sucrose, high fructose corn syrup, or fructose solutions. Rats were given access to food, water and a sugar solution for 24h, after which blood and tissues were collected. Fructose access (as opposed to other sugars that were tested) resulted in a doubling of circulating triglycerides. Glucose consumption resulted in upregulation of 7 satiety-related hypothalamic peptides whereas changes in gene expression were mixed for remaining sugars. Also, following multiple verification assays, 6 satiety related peptides were verified as being affected by sugar intake. These data provide evidence that not all sugars are equally effective in affecting the control of intake.

  15. Bariatric surgery in hypothalamic obesity

    Directory of Open Access Journals (Sweden)

    Nathan eBingham

    2012-02-01

    Full Text Available Craniopharyngiomas (CP are epithelial neoplasms generally found in the area of the pituitary and hypothalamus. Despite benign histology, these tumors and/or their treatment often result in significant, debilitating disorders of endocrine, neurological, behavioral, and metabolic systems. Severe obesity is observed in a high percentage of patients with CP resulting in significant comorbidities and negatively impacting quality of life. Obesity occurs as a result of hypothalamic damage and disruption of normal homeostatic mechanisms regulating energy balance. Such pathological weight gain, termed hypothalamic obesity (HyOb, is often severe and refractory to therapy.Unfortunately, neither lifestyle intervention nor pharmacotherapy has proven truly effective in the treatment of CP-HyOb. Given the limited choices and poor results of these treatments, several groups have examined bariatric surgery as a treatment alternative for patients with CP-HyOb. While a large body of evidence exists supporting the use of bariatric surgery in the treatment of exogenous obesity and its comorbidities, its role in the treatment of HyOb has yet to be well defined. To date, the existing literature on bariatric surgery in CP-HyOb is largely limited to case reports and series with short term follow-up. Here we review the current reports on the use of bariatric surgery in the treatment of CP-HyOb. We also compare these results to those reported for other populations of HyOb, including Prader-Willi Syndrome and patients with melanocortin signaling defects. While initial reports of bariatric surgery in CP-HyOb are promising, their limited scope makes it difficult to draw any substantial conclusions as to the long term safety and efficacy of bariatric surgery in CP-HyOb. There continues to be a need for more robust, controlled, prospective trials with long term follow-up in order to better define the role of bariatric surgery in the treatment of all types of hypothalamic

  16. Feed intake of gilts following intracerebroventicular injection of the novel hypothalamic RFamide (RFa) neuropeptide, 26RFa

    Science.gov (United States)

    RFamide (RFa) peptides have been implicated in a broad spectrum of biological processes including energy expenditure and feed intake. 26RFa is a recently discovered hypothalamic neuropeptide that altered the release of pituitary hormones and stimulated feed intake via a NPY-specific mechanism in rat...

  17. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    NARCIS (Netherlands)

    Meerlo, P; Koehl, M; van der Borght, K; Turek, FW

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine

  18. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    NARCIS (Netherlands)

    Meerlo, P; Koehl, M; van der Borght, K; Turek, FW

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine st

  19. Autoradiographic distribution of /sup 125/I-galanin binding sites in the rat central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Skofitsch, G.; Sills, M.A.; Jacobowitz, D.M.

    1986-11-01

    Galanin (GAL) binding sites in coronal sections of the rat brain were demonstrated using autoradiographic methods. Scatchard analysis of /sup 125/I-GAL binding to slide-mounted tissue sections revealed saturable binding to a single class of receptors with a Kd of approximately 0.2 nM. /sup 125/I-GAL binding sites were demonstrated throughout the rat central nervous system. Dense binding was observed in the following areas: prefrontal cortex, the anterior nuclei of the olfactory bulb, several nuclei of the amygdaloid complex, the dorsal septal area, dorsal bed nucleus of the stria terminalis, the ventral pallidum, the internal medullary laminae of the thalamus, medial pretectal nucleus, nucleus of the medial optic tract, borderline area of the caudal spinal trigeminal nucleus adjacent to the spinal trigeminal tract, the substantia gelatinosa and the superficial layers of the dorsal spinal cord. Moderate binding was observed in the piriform, periamygdaloid, entorhinal, insular cortex and the subiculum, the nucleus accumbens, medial forebrain bundle, anterior hypothalamic, ventromedial, dorsal premamillary, lateral and periventricular thalamic nuclei, the subzona incerta, Forel's field H1 and H2, periventricular gray matter, medial and superficial gray strata of the superior colliculus, dorsal parts of the central gray, peripeduncular area, the interpeduncular nucleus, substantia nigra zona compacta, ventral tegmental area, the dorsal and ventral parabrachial and parvocellular reticular nuclei. The preponderance of GAL-binding in somatosensory as well as in limbic areas suggests a possible involvement of GAL in a variety of brain functions.

  20. Changes of Leptin-hypothalamic Neuropeptide Y Axis during the Development of Type 2 Diabetes in Rats%瘦素-下丘脑神经肽Y轴在2型糖尿病大鼠发病过程中的变化

    Institute of Scientific and Technical Information of China (English)

    杨新玲; 李杰; 卢素玉; 王海芳; 郝慧瑶; 张松筠

    2014-01-01

    2 diabetes in rats. Methods Selection of clean grade 180-220 g male SD rats 110. Type 2 dia-betic rat models were established by the intraperitoneal injection of low-dose streptozotocin(15 mg/kg). Random number table to extract 20 as the normal control group fed the basal diet. The 90 diet-induced obese( DIO)rats were divided into DIO4W group(n=20),DIO8W group(n=20),and type 2 diabetes group(n=20)according to the timing of the development of model. The concentrations of serum leptin, hypothalamic NPY and the expression of hypothalamic NPY mRNA were meas-ured. Results There were significant differences in concentrations of serum leptin and hypothalamic NPY in the four groups( P<0. 05). The concentrations of serum leptin and hypothalamic NPY in DIO4W group,DIO8W group and type 2 diabetes group were significantly higher than those in normal control group( P<0. 05 ) . The concentrations of serum leptin and hypothalamic NPY in DIO8W group and type 2 diabetes group were significantly higher than those in DIO4W group(P<0. 05). The concen-trations of serum leptin and hypothalamic NPY in type 2 diabetes group were significantly higher than those in DIO8W group(P<0. 05). There were significant differences in NPY mRNA expression level among normal control group(0. 85 ± 0. 14),DIO4W group(1. 16 ±0. 15),DIO8W group(1. 53 ± 0. 14)and type 2 diabetes group(1. 79 ± 0. 13)(F=173. 320,P <0. 05). NPY mRNA expression level in DIO4W group,DIO8W group and type 2 diabetes group was significantly higher than that in nor-mal control group,respectively(P<0. 05). NPY mRNA expression level in DIO8W group and type 2 diabetes group was signif-icantly higher than that in DIO4W group,respectively(P<0. 05). NPY mRNA expression level in type 2 diabetes group was significantly higher than that in DIO8W group(P<0. 05). Concentration of serum leptin was positively correlated with concen-tration of hypothalamic NPY and NPY mRNA expression level,respectively(r=0. 951,0. 953,P<0. 05). Conclusion The

  1. Decreased hypothalamic growth hormone-releasing hormone content and pituitary responsiveness in hypothyroidism.

    OpenAIRE

    Katakami, H; Downs, T. R.; Frohman, L A

    1986-01-01

    The effects of thyroidectomy (Tx) and thyroxine replacement (T4Rx) on pituitary growth hormone (GH) secretion and hypothalamic GH-releasing hormone (GRH) concentration were compared to define the mechanism of hypothyroid-associated GH deficiency. Thyroidectomized rats exhibited a complete loss of pulsatile GH secretion with extensive reduction in GRH responsiveness and pituitary GH content. Cultured pituitary cells from Tx rats exhibited reduced GRH sensitivity, maximal GH responsiveness, and...

  2. High ambient temperature reverses hypothalamic MC4 receptor overexpression in an animal model of anorexia nervosa.

    Science.gov (United States)

    Gutiérrez, E; Churruca, I; Zárate, J; Carrera, O; Portillo, M P; Cerrato, M; Vázquez, R; Echevarría, E

    2009-04-01

    The potential involvement of the melanocortin system in the beneficial effects of heat application in rats submitted to activity-based anorexia (ABA), an analogous model of anorexia nervosa (AN), was studied. Once ABA rats had lost 20% of body weight, half of the animals were exposed to a high ambient temperature (HAT) of 32 degrees C, whereas the rest were maintained at 21 degrees C. Control sedentary rats yoked to ABA animals received the same treatment. ABA rats (21 degrees C) showed increased Melanocortin 4 (MC4) receptor and Agouti gene Related Peptide (AgRP) expression, and decreased pro-opiomelanocortin (POMC) mRNA levels (Real Time PCR), with respect to controls. Heat application increased weight gain and food intake, and reduced running rate in ABA rats, when compared with ABA rats at 21 degrees C. However, no changes in body weight and food intake were observed in sedentary rats exposed to heat. Moreover, heat application reduced MC4 receptor, AgRP and POMC expression in ABA rats, but no changes were observed in control rats. These results indicate that hypothalamic MC4 receptor overexpression could occur on the basis of the characteristic hyperactivity, weight loss, and self-starvation of ABA rats, and suggest the involvement of hypothalamic melanocortin neural circuits in behavioural changes shown by AN patients. Changes in AgRP and POMC expression could represent an adaptative response to equilibrate energy balance. Moreover, the fact that HAT reversed hypothalamic MC4 receptor overexpression in ABA rats indicates the involvement of brain melanocortin system in the reported beneficial effects of heat application in AN. A combination of MC4 receptor antagonists and heat application could improve the clinical management of AN.

  3. Distribution of type 1 cannabinoid receptor-expressing neurons in the septal-hypothalamic region of the mouse: colocalization with GABAergic and glutamatergic markers.

    Science.gov (United States)

    Hrabovszky, Erik; Wittmann, Gábor; Kalló, Imre; Füzesi, Tamás; Fekete, Csaba; Liposits, Zsolt

    2012-04-01

    Type 1 cannabinoid receptor (CB1) is the principal mediator of retrograde endocannabinoid signaling in the brain. In this study, we addressed the topographic distribution and amino acid neurotransmitter phenotype of endocannabinoid-sensitive hypothalamic neurons in mice. The in situ hybridization detection of CB1 mRNA revealed high levels of expression in the medial septum (MS) and the diagonal band of Broca (DBB), moderate levels in the preoptic area and the hypothalamic lateroanterior (LA), paraventricular (Pa), ventromedial (VMH), lateral mammillary (LM), and ventral premammillary (PMV) nuclei, and low levels in many other hypothalamic regions including the suprachiasmatic (SCh) and arcuate (Arc) nuclei. This regional distribution pattern was compared with location of γ-aminobutyric acid (GABA)ergic and glutamatergic cell groups, as identified by the expression of glutamic acid decarboxylase 65 (GAD65) and type 2 vesicular glutamate transporter (VGLUT2) mRNAs, respectively. The MS, DBB, and preoptic area showed overlaps between GABAergic and CB1-expressing neurons, whereas hypothalamic sites with moderate CB1 signals, including the LA, Pa, VMH, LM, and PMV, were dominated by glutamatergic neurons. Low CB1 mRNA levels were also present in other glutamatergic and GABAergic regions. Dual-label in situ hybridization experiments confirmed the cellular co-expression of CB1 with both glutamatergic and GABAergic markers. In this report we provide a detailed anatomical map of hypothalamic glutamatergic and GABAergic systems whose neurotransmitter release is controlled by retrograde endocannabinoid signaling from hypothalamic and extrahypothalamic target neurons. This neuroanatomical information contributes to an understanding of the role that the endocannabinoid system plays in the regulation of endocrine and metabolic functions.

  4. Rapid-onset hypoglycemia suppresses Fos expression in discrete parts of the ventromedial nucleus of the hypothalamus.

    Science.gov (United States)

    Foster, Nicholas N; Azam, Sana; Watts, Alan G

    2016-06-01

    The consensus view of the ventromedial nucleus of the hypothalamus (VMH) is that it is a key node in the rodent brain network controlling sympathoadrenal counterregulatory responses to hypoglycemia. To identify the location of hypoglycemia-responsive neurons in the VMH, we performed a high spatial resolution Fos analysis in the VMH of rats made hypoglycemic with intraperitoneal injections of insulin. We examined Fos expression in the four constituent parts of VMH throughout its rostrocaudal extent and determined their relationship to blood glucose concentrations. Hypoglycemia significantly decreased Fos expression only in the dorsomedial and central parts of the VMH, but not its anterior or ventrolateral parts. Moreover, the number of Fos-expressing neurons was significantly and positively correlated in the two responsive regions with terminal blood glucose concentrations. We also measured Fos responses in the paraventricular nucleus of the hypothalamus (PVH) and in several levels of the periaqueductal gray (PAG), which receives strong projections from the VMH. We found the expected and highly significant increase in Fos in the neuroendocrine PVH, which was negatively correlated to terminal blood glucose concentrations, but no significant differences were seen in any part of the PAG. Our results show that there are distinct populations of VMH neurons whose Fos expression is suppressed by hypoglycemia, and their numbers correlate with blood glucose. These findings support a clear division of glycemic control functions within the different parts of the VMH.

  5. 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.

  6. Pure ipsilateral central facial palsy and contralateral hemiparesis secondary to ventro-medial medullary stroke.

    Science.gov (United States)

    Ahdab, R; Saade, H S; Kikano, R; Ferzli, J; Tarcha, W; Riachi, N

    2013-09-15

    Medullary infarcts are occasionally associated with facial palsy of the central type (C-FP). This finding can be explained by the course of the facial corticobulbar (F-CB) fibers. It is believed that fibers that project to the upper facial muscles decussate at the level of the facial nucleus, whereas those destined to the lower facial muscles decussate more caudally, at the level of the mid or upper medulla. It has been proposed that the lower F-CB fibers descend ventromedially near the corticospinal tract to the upper medulla where they cross midline and ascend dorsolaterally. Accordingly, ventromedial medullary infarcts are expected to result in contralateral facial and limb weakness. We report a patient with a medial medullary infarct restricted to the right pyramid and associated with ipsilateral C-FP and contralateral hemiparesis. The neurological findings are discussed in light of the hypothetical course of the F-CB fibers in the medulla.

  7. The Interplay of Hippocampus and Ventromedial Prefrontal Cortex in Memory-Based Decision Making

    Science.gov (United States)

    Weilbächer, Regina A.; Gluth, Sebastian

    2016-01-01

    Episodic memory and value-based decision making are two central and intensively studied research domains in cognitive neuroscience, but we are just beginning to understand how they interact to enable memory-based decisions. The two brain regions that have been associated with episodic memory and value-based decision making are the hippocampus and the ventromedial prefrontal cortex, respectively. In this review article, we first give an overview of these brain–behavior associations and then focus on the mechanisms of potential interactions between the hippocampus and ventromedial prefrontal cortex that have been proposed and tested in recent neuroimaging studies. Based on those possible interactions, we discuss several directions for future research on the neural and cognitive foundations of memory-based decision making. PMID:28036071

  8. The Interplay of Hippocampus and Ventromedial Prefrontal Cortex in Memory-Based Decision Making

    Directory of Open Access Journals (Sweden)

    Regina A. Weilbächer

    2016-12-01

    Full Text Available Episodic memory and value-based decision making are two central and intensively studied research domains in cognitive neuroscience, but we are just beginning to understand how they interact to enable memory-based decisions. The two brain regions that have been associated with episodic memory and value-based decision making are the hippocampus and the ventromedial prefrontal cortex, respectively. In this review article, we first give an overview of these brain–behavior associations and then focus on the mechanisms of potential interactions between the hippocampus and ventromedial prefrontal cortex that have been proposed and tested in recent neuroimaging studies. Based on those possible interactions, we discuss several directions for future research on the neural and cognitive foundations of memory-based decision making.

  9. Dorsomedial hypothalamic NPY and energy balance control.

    Science.gov (United States)

    Bi, Sheng; Kim, Yonwook J; Zheng, Fenping

    2012-12-01

    Neuropeptide Y (NPY) is a potent hypothalamic orexigenic peptide. Within the hypothalamus, Npy is primarily expressed in the arcuate nucleus (ARC) and the dorsomedial hypothalamus (DMH). While the actions of ARC NPY in energy balance control have been well studied, a role for DMH NPY is still being unraveled. In contrast to ARC NPY that serves as one of downstream mediators of actions of leptin in maintaining energy homeostasis, DMH NPY is not under the control of leptin. Npy gene expression in the DMH is regulated by brain cholecystokinin (CCK) and other yet to be identified molecules. The findings of DMH NPY overexpression or induction in animals with increased energy demands and in certain rodent models of obesity implicate a role for DMH NPY in maintaining energy homeostasis. In support of this view, adeno-associated virus (AAV)-mediated overexpression of NPY in the DMH causes increases in food intake and body weight and exacerbates high-fat diet-induced hyperphagia and obesity. Knockdown of NPY in the DMH via AAV-mediated RNAi ameliorates hyperphagia, obesity and glucose intolerance of Otsuka Long-Evans Tokushima Fatty rats in which DMH NPY overexpression has been proposed to play a causal role. NPY knockdown in the DMH also prevents high-fat diet-induced hyperphagia, obesity and impaired glucose homeostasis. A detailed examination of actions of DMH NPY reveals that DMH NPY specifically affects nocturnal meal size and produces an inhibitory action on within meal satiety signals. In addition, DMH NPY modulates energy expenditure likely through affecting brown adipocyte formation and thermogenic activity. Overall, the recent findings provide clear evidence demonstrating critical roles for DMH NPY in energy balance control, and also imply a potential role for DMH NPY in maintaining glucose homeostasis.

  10. The Inhibitory Effects of Nesfatin-1 in Ventromedial Hypothalamus on Gastric Function and Its Regulation by Nucleus Accumbens

    Science.gov (United States)

    Gao, Shengli; Guo, Feifei; Sun, Xiangrong; Zhang, Nana; Gong, Yanling; Xu, Luo

    2017-01-01

    Aim: The aim of this study was to investigate the effect of nesfatin-1 signaling in the ventromedial hypothalamus (VMH) on gastric functions, as well as the regulation of these effects by nucleus accumbens (NAc) projections to VMH. Methods: The expression of c-fos in nesfatinergic VMH neurons induced by gastric distension (GD) was measured using the double fluoro-immunohistochemical staining. The firing rates of neurons were monitored with single-unit extracellular electric discharge recording. The projection of nesfatinergic neurons from NAc to VMH was observed by fluorogold retrograde tracer combined with fluoro-immunohistochemical staining. The effect of nesfatin-1 in VMH or electric stimulation in NAc on gastric function was studied by measuring food intake, gastric acid output, gastric motility, and gastric emptying, and the ability of the melanocortin-3/4 receptor antagonist SHU9119 or the anti-nesfatin-1 antibody to block nesfatin-1 in the VMH was assessed. Results: Expression of c-fos was observed in VMH nesfatinergic neurons following GD in rats. Further, nesfatin-1 delivery to single GD-responsive neurons changed the firing rates of these neurons in the VMH. In awake, behaving rats, intra-VMH administration of nesfatin-1 inhibited food intake, gastric acid output, gastric motility, and gastric emptying. These effects were abolished by SHU9119. Fluorogold retrograde tracing showed nesfatinergic neural projection from the NAc to the VMH. Electrical stimulation of NAc modified the firing rates of the VMH neurons and inhibited food intake and gastric functions. The pretreatment with an anti-nesfatin-1 antibody in the VMH reversed the effects of NAc electrical stimulation on the VMH neuronal firing rates and gastric function. Conclusions: Nesfatin-1 in the VMH inhibited food intake, gastric acid output, gastric motility, and gastric emptying. A nesfatinergic pathway between NAc and VMH transmitted metabolism-regulating signals. PMID:28105016

  11. Human Choice Strategy Varies with Anatomical Projections from Ventromedial Prefrontal Cortex to Medial Striatum.

    Science.gov (United States)

    Piray, Payam; Toni, Ivan; Cools, Roshan

    2016-03-09

    Two distinct systems, goal-directed and habitual, support decision making. It has recently been hypothesized that this distinction may arise from two computational mechanisms, model-based and model-free reinforcement learning, neuronally implemented in frontostriatal circuits involved in learning and behavioral control. Here, we test whether the relative strength of anatomical connectivity within frontostriatal circuits accounts for variation in human individuals' reliance on model-based and model-free control. This hypothesis was tested by combining diffusion tensor imaging with a multistep decision task known to distinguish model-based and model-free control in humans. We found large interindividual differences in the degree of model-based control, and those differences are predicted by the structural integrity of white-matter tracts from the ventromedial prefrontal cortex to the medial striatum. Furthermore, an analysis based on masking out of bottom-up tracts suggests that this effect is driven by top-down influences from ventromedial prefrontal cortex to medial striatum. Our findings indicate that individuals with stronger afferences from the ventromedial prefrontal cortex to the medial striatum are more likely to rely on a model-based strategy to control their instrumental actions. These findings suggest a mechanism for instrumental action control through which medial striatum determines, at least partly, the relative contribution of model-based and model-free systems during decision-making according to top-down model-based information from the ventromedial prefrontal cortex. These findings have important implications for understanding the neural circuitry that might be susceptible to pathological computational processes in impulsive/compulsive psychiatric disorders.

  12. Effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on hypothalamic-pituitary-adrenal axis negative feedback function in rat models of chronic stress-induced depression%慢性应激抑郁模型大鼠下丘脑-垂体-肾上腺轴负反馈功能与蒙药槟榔十三味丸的干预

    Institute of Scientific and Technical Information of China (English)

    包伍叶; 范盎然; 白亮凤; 佟海英; 于雪; 乌吉斯古冷; 李婧; 胡日乐巴根; 张月

    2014-01-01

    BACKGROUND:Mongolian Pharmaceutical Betel Shisanwei Ingredients Pil has achieved good clinical efficacy, but the underlying mechanism remains unclear. OBJECTIVE: To study the effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pil on the hypothalamic-pituitary-adrenal axis negative feedback function in the chronic depressed rats, and to explore anti-depression mechanisms of Mongolian Pharmaceutical Betel Shisanwei ingredients pil. METHODS: Eighty male Wistar rats were randomly divided into ten groups according to the sugar consumption test (with eight rats in each group): normal control group, model group, fluoxetine group, high-, medium- and low-dose Betel Shisanwei Ingredients Pil groups, RU486 group, high-, medium- and low-dose Betel Shisanwei Ingredients Pil plus RU486 groups. Except normal control group, the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely rising, to establish depression models. In the meantime, rats of the high-, medium- and low-dose Betel Shisanwei Ingredients Pil groups were given oral gavage of Betel Shisanwei Ingredients Pil (0.2, 0.4, 0.8 g/kg) for 28 days; rats of the normal control group and model group were intragstricaly administered with sodium carboxymethyl celulose; rats of RU486 group were given abdominal subcutaneous injection of RU486 from day 21 after modeling; rats of the high-, medium- and low-dose Betel Shisanwei Ingredients Pil plus RU486 groups were intragstricaly administered with Betel Shisanwei Ingredients Pil (0.2, 0.4, 0.8 g/kg) and subcutaneous injection of RU486 from day 21. RESULTS AND CONCLUSION:Compared with normal control group, cortisone content increased significantly (P < 0.05), the expression of glucocorticoid receptor mRNA in hippocampus, hypothalamus and pituitary gland decreased significantly, and hypothalamic corticotrophin releasing hormone mRNA expression increased significantly in the model group and RU486 group. Compared with model

  13. In vivo Investigation of Hypothalamic Secretory Activity.

    Science.gov (United States)

    Barkan, A L; Jaffe, C A; Padmanabhan, V

    1997-04-01

    The finding that all pituitary hormones are released in a discrete pulsatile fashion and that the pulsatile properties of the pituitary hormone secretion are altered in some physiologic and pathologic conditions prompted the development of techniques designed to study the pattern of release and the regulation of secretion of the hypothalamic neuropeptides. This review describes the currently used techniques to assess hypothalamic hormone secretion. (Trends Endocrinol Metab 1997;8:105-111). (c) 1997, Elsevier Science Inc.

  14. Normalization of hypothalamic serotonin (5-HT 1B) receptor and NPY in cancer anorexia after tumor resection: an immunocytochemical study.

    Science.gov (United States)

    Makarenko, Irina G; Meguid, Michael M; Gatto, Louis; Chen, Chung; Ramos, Eduardo J B; Goncalves, Carolina G; Ugrumov, Michael V

    2005-08-05

    Tumor growth leads to anorexia and decreased food intake, the regulation of which is via the integrated hypothalamic peptidergic and monoaminergic system. Serotonin (5-HT), an anorectic monoamine acts primarily via 5-HT 1B-receptors in hypothalamic nuclei while neuropeptide Y (NPY) acts an orexigenic peptide. We previously reported that 5-HT 1B-receptors are up regulated while NPY is down regulated in tumor-bearing (TB)-related anorexia, contributing to food intake reduction. In anorectic TB rats we hypothesize that after tumor resection when food intake has reverted to normal, normalization of 5-HT 1B-receptor and NPY will occur. The aim of this study was to demonstrate normalization of these hypothalamic changes compared to Controls. In anorectic tumor-bearing rats after tumor resection (TB-R) and in sham-operated (Control) rats, distribution of 5-HT 1B-receptors and NPY in hypothalamic nuclei was analyzed using peroxidase antiperoxidase immunocytochemical methods. Image analysis of immunostaining was performed and the data were statistically analyzed. Immunostaining specificity was controlled by omission of primary or secondary antibodies and pre-absorption test. Our results show that after TB-R versus Controls a normalization of food intake, 5-H-1B-receptor and NPY expression in the hypothalamus occurs. These data, discussed in context with our previous studies, support the hypothesis that tumor resection results not only in normalization of food intake but also in reversible changes of anorectic and orexigenic hypothalamic modulators.

  15. Hypothalamic control of adipose tissue.

    Science.gov (United States)

    Stefanidis, A; Wiedmann, N M; Adler, E S; Oldfield, B J

    2014-10-01

    A detailed appreciation of the control of adipose tissue whether it be white, brown or brite/beige has never been more important to the development of a framework on which to build therapeutic strategies to combat obesity. This is because 1) the rate of fatty acid release into the circulation from lipolysis in white adipose tissue (WAT) is integrally important to the development of obesity, 2) brown adipose tissue (BAT) has now moved back to center stage with the realization that it is present in adult humans and, in its activated form, is inversely proportional to levels of obesity and 3) the identification and characterization of "brown-like" or brite/beige fat is likely to be one of the most exciting developments in adipose tissue biology in the last decade. Central to all of these developments is the role of the CNS in the control of different fat cell functions and central to CNS control is the integrative capacity of the hypothalamus. In this chapter we will attempt to detail key issues relevant to the structure and function of hypothalamic and downstream control of WAT and BAT and highlight the importance of developing an understanding of the neural input to brite/beige fat cells as a precursor to its recruitment as therapeutic target.

  16. Expression of GnRH in the hypothalamic arcuate nucleus in rats with diet-induced obesity and its influence on spermatogenesis%营养性肥胖大鼠弓状核促性腺激素释放激素的表达变化以及对精子发生的影响

    Institute of Scientific and Technical Information of China (English)

    刘冉冉; 赵方欣; 张洪芹

    2013-01-01

    Objective:To investigate the expressions of neuropeptide Y (NPY), obesity receptor (ob-R) and gonadotropin-re-leasing hormone (GnRH) in the hypothalamic arcuate nucleus in rats with diet-induced obesity and its influence on spermatogenesis. Methods:Weanling SD male rats were fed with high-energy feed. After 14 weeks, obesity models were selected according to Lee's Index. The rats in the control group were established by feeding them with normal feed. We observed the expressions of NPY. ob-R and GnRH in the hypothalamic arcuate nucleus and the expression of androgen binding protein (ABP) in the testis and the changes of spermatogenic cells cycle with obesity. We also detected the level of leptin,follicule-stimula-ting hormone (FSH), luteinizing hormone (LH) in serum and the concentration of testosterone in venous blood of testicle. Results:The level of leptin was higher in the obesity group than in the control group. The levels of testosterone, FSH and LH were lower than that in the control group. The expression of NPY increased, and the expressions of ob-R and GnRH decreased, as compared with the control group. The expression of ABP in testicles in obesity models was attenuated. The spermatogenic cells in S phase in obesity model decreased, while the cells in G2/M phase significantly increased. Conclusion:The low level of GnRH induced by neuroendocrine metabolic disorder lead to dysfunction of hypothalamic-pituitarytesticular axis, resulting in impediment of spermatogenesis, which might result in infertility.%目的:探讨营养性肥胖大鼠弓状核神经肽Y(NPY)、瘦素受体(ob-R)及与生殖相关的促性腺激素释放激素(GnRH)表达变化以及对精子发生的影响.方法:免疫组织化学观察NPY、ob R及GnRH在肥胖模型组下丘脑弓状核的表达情况以及睾丸支持细胞雄激素结合蛋白(ABP)表达变化;流式细胞分析检测睾丸生精细胞周期的改变.并测定血清中瘦素、睾酮、卵泡

  17. Inhibitory role of the serotonergic system on estrogen receptor α expression in the female rat hypothalamus.

    Science.gov (United States)

    Ito, Hiroyuki; Shimogawa, Yuji; Kohagura, Daisuke; Moriizumi, Tetsuji; Yamanouchi, Korehito

    2014-11-07

    The role of the serotonergic system in regulating the expression of estrogen receptor (ER) α in the hypothalamus was investigated in ovariectomized rats by injecting a serotonin synthesis inhibitor, parachlorophenylalanine (PCPA), or by destroying the dorsal raphe nucleus (DR). The number of ERα-immunoreactive (ir) cells was counted in the anteroventral periventricular nucleus in the preoptic area (AVPV), ventrolateral ventromedial hypothalamic nucleus (vlVMN), and arcuate nucleus (ARCN). Seven days after ovariectomy, 100mg/kg PCPA or saline was injected daily for 4 days. Alternatively, radiofrequency lesioning of the DR (DRL) or sham lesions were made on the same time of ovariectomy. One-day after the last injection of PCPA or 7 days after brain surgery, the brain was fixed for immunostaining of ERα and the number of ERα-ir cell were counted in the nuclei of interest. The mean number of ERα-ir cells/mm(3) (density) in the AVPV of the PCPA or DRL groups was statistically higher than that in the saline or sham group. In the vlVMN and ARCN of the PCPA or DRL groups, the mean density of ERα-ir cells was comparable to the saline or sham groups. These results suggest that the serotonergic system of the DR plays an inhibitory role on the expression of ERα in the AVPV, but not in the vlVMN and ARCN. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic-Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters

    Directory of Open Access Journals (Sweden)

    Li-Li Wu

    2016-01-01

    Full Text Available The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA and water-EtOH soluble fraction (Fraction B, FB prepared from the Danzhi-xiaoyao-san (DZXYS by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats.

  19. Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.

    Science.gov (United States)

    Farman, H H; Windahl, S H; Westberg, L; Isaksson, H; Egecioglu, E; Schele, E; Ryberg, H; Jansson, J O; Tuukkanen, J; Koskela, A; Xie, S K; Hahner, L; Zehr, J; Clegg, D J; Lagerquist, M K; Ohlsson, C

    2016-08-01

    Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice.

  20. Hypothalamic dysfunction following whole-brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Mechanick, J.I.; Hochberg, F.H.; LaRocque, A.

    1986-10-01

    The authors describe 15 cases with evidence of hypothalamic dysfunction 2 to 9 years following megavoltage whole-brain x-irradiation for primary glial neoplasm. The patients received 4000 to 5000 rads in 180- to 200-rad fractions. Dysfunction occurred in the absence of computerized tomography-delineated radiation necrosis or hypothalamic invasion by tumor, and antedated the onset of dementia. Fourteen patients displayed symptoms reflecting disturbances of personality, libido, thirst, appetite, or sleep. Hyperprolactinemia (with prolactin levels up to 70 ng/ml) was present in all of the nine patients so tested. Of seven patients tested with thyrotropin-releasing hormone, one demonstrated an abnormal pituitary gland response consistent with a hypothalamic disorder. Seven patients developed cognitive abnormalities. Computerized tomography scans performed a median of 4 years after tumor diagnosis revealed no hypothalamic tumor or diminished density of the hypothalamus. Cortical atrophy was present in 50% of cases and third ventricular dilatation in 58%. Hypothalamic dysfunction, heralded by endocrine, behavioral, and cognitive impairment, represents a common, subtle form of radiation damage.

  1. Bardoxolone methyl prevents obesity and hypothalamic dysfunction.

    Science.gov (United States)

    Camer, Danielle; Yu, Yinghua; Szabo, Alexander; Wang, Hongqin; Dinh, Chi H L; Huang, Xu-Feng

    2016-08-25

    High-fat (HF) diet-induced obesity is associated with hypothalamic leptin resistance and low grade chronic inflammation, which largely impairs the neuroregulation of negative energy balance. Neuroregulation of negative energy balance is largely controlled by the mediobasal and paraventricular nuclei regions of the hypothalamus via leptin signal transduction. Recently, a derivative of oleanolic acid, bardoxolone methyl (BM), has been shown to have anti-inflammatory effects. We tested the hypothesis that BM would prevent HF diet-induced obesity, hypothalamic leptin resistance, and inflammation in mice fed a HF diet. Oral administration of BM via drinking water (10 mg/kg daily) for 21 weeks significantly prevented an increase in body weight, energy intake, hyperleptinemia, and peripheral fat accumulation in mice fed a HF diet. Furthermore, BM treatment prevented HF diet-induced decreases in the anorexigenic effects of peripheral leptin administration. In the mediobasal and paraventricular nuclei regions of the hypothalamus, BM administration prevented HF diet-induced impairments of the downstream protein kinase b (Akt) pathway of hypothalamic leptin signalling. BM treatment also prevented an increase in inflammatory cytokines, tumour necrosis factor alpha (TNFα) and interleukin 6 (IL-6) in these two hypothalamic regions. These results identify a potential novel neuropharmacological application for BM in preventing HF diet-induced obesity, hypothalamic leptin resistance, and inflammation.

  2. Neuroanatomy and physiology of the avian hypothalamic/pituitary axis: clinical aspects.

    Science.gov (United States)

    Ritchie, Midge

    2014-01-01

    This article describes the anatomy of the avian hypothalamic/pituitary axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the somatotrophic axis, and neurohypophysis.

  3. Hypothalamic neuronal histamine modulates febrile response but not anorexia induced by lipopolysaccharide.

    Science.gov (United States)

    Chiba, Seiichi; Itateyama, Emi; Oka, Kyoko; Masaki, Takayuki; Sakata, Toshiie; Yoshimatsu, Hironobu

    2005-05-01

    This study examined the contribution of hypothalamic neuronal histamine (HA) to the anorectic and febrile responses induced by lipopolysaccharide (LPS), an exogenous pyrogen, and the endogenous pyrogens interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Intraperitoneal (ip) injection of LPS, IL-1beta, or TNF-alpha suppressed 24-hr cumulative food intake and increased rectal temperature in rats. To analyze the histaminergic contribution, rats were pretreated with intracerebroventricular (icv) injection of 2.44 mmol/kg or ip injection of 244 mmol/kg of alpha-fluoromethylhistidine (FMH), a suicide inhibitor of histidine decarboxylase (HDC), to deplete neural HA. The depletion of neural HA augmented the febrile response to ip injection of LPS and IL-1beta and alleviated the anorectic response to ip injection of IL-1beta. However, the depletion of neural HA did not modify the LPS-induced anorectic response or TNF-alpha-induced febrile and anorectic responses. Consistent with these results, the rate of hypothalamic HA turnover, assessed by the accumulation of tele-methylhistamine (t-MH), was elevated with ip injections of LPS and IL-1beta, but unaffected by TNF-alpha at equivalent doses. This suggests that (i) LPS and IL-1beta activate hypothalamic neural HA turnover; (ii) hypothalamic neural HA suppresses the LPS- and IL-1beta-induced febrile responses and accelerates the IL-1beta-induced anorectic response; and (iii) TNF-alpha modulates the febrile and anorectic responses via a neural HA-independent pathway. Therefore, hypothalamic neural HA is involved in the IL-1beta-dominant pathway, rather than the TNF-alpha-dominant pathway, preceding the systemic inflammatory response induced by exogenous pyrogens, such as LPS. Further research on this is needed.

  4. Genetic, hypothalamic and endocrine features of clinical and experimental obesity.

    Science.gov (United States)

    Bray, G A

    1992-01-01

    Obesity occurs in both clinical and animal forms in a variety of specific models which allow study of its underlining endocrine and mechanistic features. Among the neuroendocrine varieties of obesity, polycystic ovaries are probably the most common. The importance of the gonadal feedback system for regulation of food intake and obesity is indicated by the effects of castration in experimental animals which is a widely used mechanism for producing experimental obesity. Cushing syndrome and hypothalamic obesity are rare clinical syndromes. The current evidence suggests that there are two types of hypothalamic obesity from a mechanistic point of view--one associated with hyperphagia as a necessary and sufficient cause and a disturbance of the autonomic nervous system without hyperphagia as a second mechanism. Although genetic factors underlie most types of human obesity, there are several dymorphic forms of obesity including the Prader-Willy syndrome, Cohen's syndrome, Carpenter's syndrome, Ahlstrom's syndrome and the Bardet-Biedel syndrome. The Prader-Willi syndrome is characterized by obesity hypotonia hypogonadism and mental retardation. In animals, a dominant form of inheritance of obesity is seen in the yellow mouse. Current evidence suggests that this syndrome can be explained by reduced acetylation of MSH in the pituitary and/or hypothalamus. Several recessively inherited forms of obesity exist including the obese mouse, the diabetes mouse, fatty rat, the fat mouse, tubby mouse and the corpulent rat. In addition, there are a number of polygenic types of experimental obesity. The final mechanistic classification of obesity are those due to dietary manipulation. For both human beings and animals, a highly fat diet appears to be particularly problematic for the development of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Sex-Specific Control of Fat Mass and Counterregulation by Hypothalamic Glucokinase.

    Science.gov (United States)

    Steinbusch, Laura K M; Picard, Alexandre; Bonnet, Marion S; Basco, Davide; Labouèbe, Gwenaël; Thorens, Bernard

    2016-10-01

    Glucokinase (Gck) is a critical regulator of glucose-induced insulin secretion by pancreatic β-cells. It has been suggested to also play an important role in glucose signaling in neurons of the ventromedial hypothalamic nucleus (VMN), a brain nucleus involved in the control of glucose homeostasis and feeding. To test the role of Gck in VMN glucose sensing and physiological regulation, we studied mice with genetic inactivation of the Gck gene in Sf1 neurons of the VMN (Sf1Gck(-/-) mice). Compared with control littermates, Sf1Gck(-/-) mice displayed increased white fat mass and adipocyte size, reduced lean mass, impaired hypoglycemia-induced glucagon secretion, and a lack of parasympathetic and sympathetic nerve activation by neuroglucopenia. However, these phenotypes were observed only in female mice. To determine whether Gck was required for glucose sensing by Sf1 neurons, we performed whole-cell patch clamp analysis of brain slices from control and Sf1Gck(-/-) mice. Absence of Gck expression did not prevent the glucose responsiveness of glucose-excited or glucose-inhibited Sf1 neurons in either sex. Thus Gck in the VMN plays a sex-specific role in the glucose-dependent control of autonomic nervous activity; this is, however, unrelated to the control of the firing activity of classical glucose-responsive neurons.

  6. 乙烯雌酚对雌鼠生殖内分泌及下丘脑ERαmRNA表达的影响%The effects of sex steroid hormones on reproductive endocrine and hypothalamic ERαmRNA expression in the female rats

    Institute of Scientific and Technical Information of China (English)

    阴奇男

    2011-01-01

    Purpose To observe the effects of sex steroid hormones on reproductive endocrine and hypothalamic ERαmRNA expression in the female rats. Methods 16 rats from 32 female rats were randomly taken for the control group,and the remaining 16 rats were taken to couduct surgery and ovariectomy( tail clamp method was made), and after the success of modeling, it is the observation group. Each group was fed continuously for 4 weeks. Morphology of reproductive hormones and reverse transcription polymerase chain reaction (RT-PCR) were used to assay the hypothalamus,pituitary ERαmRNA expression. Results Compared with the normal control group,the wet weight index decreased significantly (P < 0.01 ) in the observation group. At the same time there were significant changes in uterine morphology. The expression of hypothalamus,pituitary ERαmRNA in the observation group was significantly decreased compared with the control group (P < 0.05). Conclusion The sex steroid hormones not only have an important physiological role on the reproductive system,and but also have an important role in the hypothalamus especially on the nervous system. The mechanism may be associated with elevated hypothalamic, pituitary ERαmRNA expression.%目的 观察性类固醇激素--乙烯雌酚对雌鼠生殖内分泌及下丘脑ERamRNA表达的影响.方法 健康大鼠32只随机取16只作正常对照组,其余16只均采取双侧卵巢切除手术加夹尾激怒法造模,造模成功后为观察组.两组分别连续灌胃生理盐水与乙烯雌酚4周,采用形态学观察生殖内分泌情况,采用逆转录聚合酶链反应(RT-PCR)法测定大鼠下丘脑ERαmRNA表达.结果 与正常对照组比较,观察组大鼠肾上腺湿重系明显降低(P<0.01).同时子宫形态也有明显变化.观察组大鼠下丘脑ERαmRNA的表达明显下降(P<0.05).结论 乙烯雌酚不仅对生殖系统有重要的生理作用,而且对神经系统尤其是下丘脑也具有重要作用.其作用机制

  7. Distinct effects of leptin and a melanocortin receptor agonist injected into medial hypothalamic nuclei on glucose uptake in peripheral tissues.

    Science.gov (United States)

    Toda, Chitoku; Shiuchi, Tetsuya; Lee, Suni; Yamato-Esaki, Maya; Fujino, Yusuke; Suzuki, Atsushi; Okamoto, Shiki; Minokoshi, Yasuhiko

    2009-12-01

    The medial hypothalamus mediates leptin-induced glucose uptake in peripheral tissues, and brain melanocortin receptors (MCRs) mediate certain central effects of leptin. However, the contributions of the leptin receptor and MCRs in individual medial hypothalamic nuclei to regulation of peripheral glucose uptake have remained unclear. We examined the effects of an injection of leptin and the MCR agonist MT-II into medial hypothalamic nuclei on glucose uptake in peripheral tissues. Leptin or MT-II was injected into the ventromedial (VMH), dorsomedial (DMH), arcuate nucleus (ARC), or paraventricular (PVH) hypothalamus or the lateral ventricle (intracerebroventricularly) in freely moving mice. The MCR antagonist SHU9119 was injected intracerebroventricularly. Glucose uptake was measured by the 2-[(3)H]deoxy-d-glucose method. Leptin injection into the VMH increased glucose uptake in skeletal muscle, brown adipose tissue (BAT), and heart, whereas that into the ARC increased glucose uptake in BAT, and that into the DMH or PVH had no effect. SHU9119 abolished these effects of leptin injected into the VMH. Injection of MT-II either into the VMH or intracerebroventricularly increased glucose uptake in skeletal muscle, BAT, and heart, whereas that into the PVH increased glucose uptake in BAT, and that into the DMH or ARC had no effect. The VMH mediates leptin- and MT-II-induced glucose uptake in skeletal muscle, BAT, and heart. These effects of leptin are dependent on MCR activation. The leptin receptor in the ARC and MCR in the PVH regulate glucose uptake in BAT. Medial hypothalamic nuclei thus play distinct roles in leptin- and MT-II-induced glucose uptake in peripheral tissues.

  8. Ontogenetic studies of tolerance development: effects of chronic morphine on the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Little, P J; Kuhn, C M

    1995-11-01

    Endogenous opiates are important regulators of the hypothalamic-pituitary-adrenal (HPA) axis in rats. Tolerance clearly develops to morphine-induced stimulation of the HPA axis in adult rats (Ignar and Kuhn 1990). The goal of the present study was to determine whether tolerance to morphine-induced stimulation of the HPA axis developed in neonatal and weanling rats treated chronically with morphine. Rats were injected with morphine or saline between days 4-8 postnatal (pups) or days 21-25 (weanlings) and tolerance assessed by determining dose-response curves for ACTH and corticosterone secretion following an acute morphine challenge. Weanlings displayed marked tolerance to the stimulation of ACTH and corticosterone secretion by morphine. Tolerance was also observed in pups to morphine-stimulated ACTH and corticosterone release. These findings suggest that the relative adaptability of the HPA axis to chronic morphine in neonatal and weanling rats is similar.

  9. Paradoxical sleep deprivation activates hypothalamic nuclei that regulate food intake and stress response.

    Science.gov (United States)

    Galvão, Milene de Oliveira Lara; Sinigaglia-Coimbra, Rita; Kawakami, Suzi Emiko; Tufik, Sergio; Suchecki, Deborah

    2009-09-01

    A large body of evidence has shown that prolonged paradoxical sleep deprivation (PSD) results in hypothalamic-pituitary-adrenal (HPA) axis activation, and in loss of body weight despite an apparent increase of food intake, reflecting increased energy expenditure. The flowerpot technique for PSD is an efficient paradigm for investigating the relationships among metabolic regulation and stress response. The purpose of the present study was to examine the mechanisms involved in the effects of 96 h of PSD on metabolism regulation, feeding behaviour and stress response by studying corticotrophin-releasing hormone (CRH) and orexin (ORX) immunoreactivity in specific hypothalamic nuclei. Once-daily assessments of body weight, twice-daily measurements of (spillage-corrected) food intake, and once-daily determinations of plasma adrenocorticotropic hormone (ACTH) and corticosterone were made throughout PSD or at corresponding times in control rats (CTL). Immunoreactivity for CRH in the paraventricular nucleus of the hypothalamus and for ORX in the hypothalamic lateral area was evaluated at the end of the experimental period. PSD resulted in increased diurnal, but not nocturnal, food intake, producing no significant changes in global food intake. PSD augmented the immunoreactivity for CRH and plasma ACTH and corticosterone levels, characterizing activation of the HPA axis. PSD also markedly increased the ORX immunoreactivity. The average plasma level of corticosterone correlated negatively with body weight gain throughout PSD. These results indicate that augmented ORX and CRH immunoreactivity in specific hypothalamic nuclei may underlie some of the metabolic changes consistently described in PSD.

  10. 腹内侧前额叶的相关研究%Research on Ventromedial Prefrontal Cortex

    Institute of Scientific and Technical Information of China (English)

    秦玲玲

    2014-01-01

    Ventromedial prefrontal cortex is a complex area, now for its specific description, there is controversy, it also has complex function. This paper combines the research before ventromedial prefrontal, elaborated on the front of several ventromedial prefrontal brain regions division method, as well as the role in emotional management, reward valuation, de-cision-making.%腹内侧前额叶是一个复杂的区域,对它的具体描述现在还有争议,它的功能也是复杂繁多。本文综合了腹内侧前额叶的相关研究,阐述了几种对腹内侧前额叶脑区划分方法,以及在情绪管理、奖赏价值评估、决策中的作用。

  11. Hyperprolactinemia from radiation-induced hypothalamic hypopituitarism

    Energy Technology Data Exchange (ETDEWEB)

    Corkill, G.; Hanson, F.W.; Gold, E.M.; White, V.A.

    1980-01-01

    In 1975 Samaan et al., described the effects of radiation damage of the hypothalamus in 15 patients with head and neck cancer. Shalet et al., in 1977 described endocrine morbidity in adults who as children had been irradiated for brain tumors. This report describes instances of hyperprolactinemia and associated hypothalamic, pituitary, and thyroid dysfunction following irradiation of a young adult female for brain neoplasia.

  12. Hypothalamic inflammation and gliosis in obesity.

    Science.gov (United States)

    Dorfman, Mauricio D; Thaler, Joshua P

    2015-10-01

    Hypothalamic inflammation and gliosis are recently discovered mechanisms that may contribute to obesity pathogenesis. Current research in this area suggests that investigation of these central nervous system responses may provide opportunities to develop new weight loss treatments. In rodents, hypothalamic inflammation and gliosis occur rapidly with high-fat diet consumption prior to significant weight gain. In addition, sensitivity or resistance to diet-induced obesity in rodents generally correlates with the presence or absence of hypothalamic inflammation and reactive gliosis (brain response to injury). Moreover, functional interventions that increase or decrease inflammation in neurons and glia correspondingly alter diet-associated weight gain. However, some conflicting data have recently emerged that question the contribution of hypothalamic inflammation to obesity pathogenesis. Nevertheless, several studies have detected gliosis and disrupted connectivity in obese humans, highlighting the potential translational importance of this mechanism. There is growing evidence that obesity is associated with brain inflammation in humans, particularly in the hypothalamus where its presence may disrupt body weight control and glucose homeostasis. More work is needed to determine whether this response is common in human obesity and to what extent it can be manipulated for therapeutic benefit.

  13. Role of developmental factors in hypothalamic function

    Directory of Open Access Journals (Sweden)

    Jakob eBiran

    2015-04-01

    Full Text Available The hypothalamus is a brain region which regulates homeostasis by mediating endocrine, autonomic and behavioral functions. It is comprised of several nuclei containing distinct neuronal populations producing neuropeptides and neurotransmitters that regulate fundamental body functions including temperature and metabolic rate, thirst and hunger, sexual behavior and reproduction, circadian rhythm, and emotional responses. The identity, number and connectivity of these neuronal populations are established during the organism’s development and are of crucial importance for normal hypothalamic function. Studies have suggested that developmental abnormalities in specific hypothalamic circuits can lead to obesity, sleep disorders, anxiety, depression and autism. At the molecular level, the development of the hypothalamus is regulated by transcription factors, secreted growth factors, neuropeptides and their receptors. Recent studies in zebrafish and mouse have demonstrated that some of these molecules maintain their expression in the adult brain and subsequently play a role in the physiological functions that are regulated by hypothalamic neurons. Here, we summarize the involvement of some of the key developmental factors in hypothalamic development and function by focusing on the mouse and zebrafish genetic model organisms.

  14. Evolution of Gelastic Epilepsy with Hypothalamic Hamartoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-11-01

    Full Text Available The patterns of clinical presentation, evolution of the epilepsy, and electoclinical diagnostic features of hypothalamic hamartoma (HH in 19 patients (8 children and 11 adults, seen between 1991 and 2001, were evaluated at Kings College Hospital and the Institute of Epileptology, London, UK.

  15. Hypothalamic functions in patients with pituitary insufficiency

    NARCIS (Netherlands)

    Borgers, A.J.F.

    2013-01-01

    The main objective of this thesis is to increase our understanding of hypothalamic (dys)function in patients with pituitary insufficiency. This goal is driven by the clinical experience of persisting symptoms in patients adequately treated for pituitary insufficiency. We focus primarily on patients

  16. MRI of hypothalamic hamartomas in children

    Energy Technology Data Exchange (ETDEWEB)

    Barral, V.; Brunelle, F.; Brauner, R.; Rappaport, R.; Lallemand, D.

    1988-09-01

    The purpose of this paper is to study the MRI characteristics of hypothalamic hamartomas of which only one case has been reported to our knowledge. Radiological studies were normal X-ray studies of the skull and sella turcica and CT studies.

  17. The role of the ventromedial prefrontal cortex in purchase intent among older adults

    Directory of Open Access Journals (Sweden)

    Bryan P Koestner

    2016-08-01

    Full Text Available Older adults are frequently the targets of scams and deception, with millions of individuals being affected each year in the United States alone. Previous research has shown that the ventromedial prefrontal cortex may play a role in vulnerability to fraud. The current study examined brain activation patterns in relation to susceptibility to scams and fraud using functional magnetic resonance imaging. Twenty-eight healthy, community-dwelling older adults were subdivided into groups of impaired and unimpaired decision makers as determined by their performance on the Iowa Gambling Task. While in the scanner, the participants viewed advertisements that were created directly from cases deemed deceptive by the Federal Trade Commission. We then obtained behavioral measures involving comprehension of claims and purchase intentions of the product in each advertisement. Contrasts show brain activity in the ventromedial prefrontal cortex was less correlated with purchase intention in impaired versus unimpaired older adult decision makers. Our results have important implications for both future research and recognizing the possible causes of fraud susceptibility among older adults.

  18. Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance

    Science.gov (United States)

    Quiñones, Mar; Al-Massadi, Omar; Gallego, Rosalía; Fernø, Johan; Diéguez, Carlos; López, Miguel; Nogueiras, Ruben

    2015-01-01

    Objective Glucagon receptor antagonists and humanized glucagon antibodies are currently studied as promising therapies for obesity and type II diabetes. Among its variety of actions, glucagon reduces food intake, but the molecular mechanisms mediating this effect as well as glucagon resistance are totally unknown. Methods Glucagon and adenoviral vectors were administered in specific hypothalamic nuclei of lean and diet-induced obese rats. The expression of neuropeptides controlling food intake was performed by in situ hybridization. The regulation of factors of the glucagon signaling pathway was assessed by western blot. Results The central injection of glucagon decreased feeding through a hypothalamic pathway involving protein kinase A (PKA)/Ca2+-calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK)-dependent mechanism. More specifically, the central injection of glucagon increases PKA activity and reduces protein levels of CaMKKβ and its downstream target phosphorylated AMPK in the hypothalamic arcuate nucleus (ARC). Consistently, central glucagon significantly decreased AgRP expression. Inhibition of PKA and genetic activation of AMPK in the ARC blocked glucagon-induced anorexia in lean rats. Genetic down-regulation of glucagon receptors in the ARC stimulates fasting-induced hyperphagia. Although glucagon was unable to decrease food intake in DIO rats, glucagon sensitivity was restored after inactivation of CaMKKβ, specifically in the ARC. Thus, glucagon decreases food intake acutely via PKA/CaMKKβ/AMPK dependent pathways in the ARC, and CaMKKβ mediates its obesity-induced hypothalamic resistance. Conclusions This work reveals the molecular underpinnings by which glucagon controls feeding that may lead to a better understanding of disease states linked to anorexia and cachexia. PMID:26909312

  19. Expressions of hypothalamic KISS-1 and G protein-couple receptor 54 genes in female rats with precocious puberty%KISS-1和GPR54基因在雌性性早熟大鼠下丘脑中的表达

    Institute of Scientific and Technical Information of China (English)

    葛伟; 王海莲; 薛江

    2012-01-01

    Objective To investigate expressions of hypothalamic KISS-1 and G protein-couple receptor 54 (GPR54) genes in female rats with precocious puberty and their effects on development of precocious puberty. Methods Fifty 26-day-old female rats were randomly divided into 5 groups, the first experimental group, the second experimental group, the first control group, the second control group, and the third control group. Experimental groups received a subcutaneous injection of N-methyl-DL-aspartate acid (NMA) twice a day until vaginal opening(VO) occurred, while control groups received normal saline. Parameters of puberty were analyzed, including the day of VO, estrous cycle of the rat, index of the ovary, index of the uterus, incidence of the corpora lutea, thickness of the uterus and serum lutein-izing hormone(LH). Expressions of hypothalamic KISS-1 and GPR54 genes in the five groups were detected by Realtime reverse transcription polymerase chain reaction (Real-time RT-FCR). Results The age of VO and first diestrus in experimental groups were earlier than in control groups(P<0.05). All parameters of puberty gradually increased with the development of puberty (P<0.05). In the same puberty developmental stage, parameters in experimental groups were not different from those in control groups (P>0.05). Conclusion Expressions of KISS-I and GPRS4 genes are associated with developmental stages of puberty, indicating that KISS-1 and GPR54 genes may play important roles in onset and development of true precocious puberty.%目的 研究KISS-1和GPR54基因在雌性性早熟大鼠下丘脑中的表达,探讨其在性早熟发生中的作用.方法 将雌性26日龄SD大鼠50只随机分为实验1组、实验2组、对照1组、对照2组、对照3组.实验组皮下注射N-甲基-D,L-天冬氨酸(NMA)每天2次直至阴道开放,对照组注射生理盐水,观察大鼠阴道开放时间及性周期,测量子宫指数、卵巢指教、卵巢黄体出现率、子宫壁厚度

  20. 不同针刺方法对慢性应激抑郁大鼠下丘脑CRH基因表达及血清ACTH、CORT的影响%Influences of different acupuncture methods on hypothalamic CRH mRNA expression and serum ACTH and CORT in rats with chronic stress depression

    Institute of Scientific and Technical Information of China (English)

    梁佳; 卢峻; 王俊仁; 崔善福; 阿英格; 图娅

    2012-01-01

    Objective To compare and observe the differences between the influences of acupuncture and electroacupuncture on the expression of hypothalamic corticotrophin-releasing hormone ( CRH) mRNA and content of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in rat model of chronic stress depression, and investigate the mechanism of acupuncture and electroacupuncture in intervene and treatment of depression. Methods All SD rats were randomly divided into Wank group, model group, acupuncture group and electroacupuncture group. The expression of hypothalamic CRH mRNA was detected by using real-time fluorescence quantitative polymerase chain reaction (RT-PCR), and content of serum ACTH and CORT were detected by applying enzyme-linked immunosorbent assay (ELJSA). Results Compared with blank group, the expression of CRH mRNA and content of serum ACTH and CORT increased significantly in model group (P 0.05) , and ACTH expression decreased significantly (P 0. 05). Conclusion The rat model of chronic stress depression had a hyperactivity of HPA axis. Acupuncture and electroacupuncture can down-regulate the function of HPA axis. It may be one of ways to treat depression with acupuncture and electroacupuncture that they have antagonism to the hyperactivity of HPA axis.%目的 对比观察手针与电针对慢性应激抑郁模型大鼠下丘脑促肾上腺皮质激素释放激素(CRH)mRNA表达及血清促肾上腺皮质激素(ACTH)、皮质酮(CORT)影响的差异,探讨手针与电针干预治疗抑郁症的机制.方法 将SD大鼠随机分为4组:空白组、模型组、手针组、电针组,采用实时荧光定量PCR (RT-PCR)方法检测下丘脑CRH mRNA含量,酶联免疫吸附法(ELISA)检测大鼠血清ACTH、CORT含量.结果 与空白组相比,模型组大鼠下丘脑CRH mRNA的含量显著升高(P<0.01),血清CORT和ACTH含量显著升高(P<0.01).与模型组相比,手针组与电针组大鼠下丘脑CRH mRNA的含量均明显降低(P<0.05

  1. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia.

    Science.gov (United States)

    Yakabi, Koji; Sadakane, Chiharu; Noguchi, Masamichi; Ohno, Shino; Ro, Shoki; Chinen, Katsuya; Aoyama, Toru; Sakurada, Tomoya; Takabayashi, Hideaki; Hattori, Tomohisa

    2010-08-01

    Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients' quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

  2. Fluorescent visualisation of the hypothalamic oxytocin neurones activated by cholecystokinin-8 in rats expressing c-fos-enhanced green fluorescent protein and oxytocin-monomeric red fluorescent protein 1 fusion transgenes.

    Science.gov (United States)

    Katoh, A; Shoguchi, K; Matsuoka, H; Yoshimura, M; Ohkubo, J-I; Matsuura, T; Maruyama, T; Ishikura, T; Aritomi, T; Fujihara, H; Hashimoto, H; Suzuki, H; Murphy, D; Ueta, Y

    2014-05-01

    The up-regulation of c-fos gene expression is widely used as a marker of neuronal activation elicited by various stimuli. Anatomically precise observation of c-fos gene products can be achieved at the RNA level by in situ hybridisation or at the protein level by immunocytochemistry. Both of these methods are time and labour intensive. We have developed a novel transgenic rat system that enables the trivial visualisation of c-fos expression using an enhanced green fluorescent protein (eGFP) tag. These rats express a transgene consisting of c-fos gene regulatory sequences that drive the expression of a c-fos-eGFP fusion protein. In c-fos-eGFP transgenic rats, robust nuclear eGFP fluorescence was observed in osmosensitive brain regions 90 min after i.p. administration of hypertonic saline. Nuclear eGFP fluorescence was also observed in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) 90 min after i.p. administration of cholecystokinin (CCK)-8, which selectively activates oxytocin (OXT)-secreting neurones in the hypothalamus. In double transgenic rats that express c-fos-eGFP and an OXT-monomeric red fluorescent protein 1 (mRFP1) fusion gene, almost all mRFP1-positive neurones in the SON and PVN expressed nuclear eGFP fluorescence 90 min after i.p. administration of CCK-8. It is possible that not only a plane image, but also three-dimensional reconstruction image may identify cytoplasmic vesicles in an activated neurone at the same time.

  3. Effect of Jingqianping Granules and Jingqianshu Granules on Expression of Hypothalamic γ-Aminobutyric Acid B2 Receptor in Emotional Rats Models of Anger-out and Anger-in%经前平和经前舒颗粒对愤怒郁怒情绪模型大鼠下丘脑γ氨基丁酸B2受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    姜英凤; 薛玲

    2011-01-01

    Objective To investigate the expression of "γ-aminobutyric acid B2 receptor (GABABR2)in rats models of anger-out and anger-in, and to explore the intervention mechanism of liver-regulating compound Formulas of Jingqianping Granule and Jingqianshu Granules. Methods The emotional models of anger-out and anger-in were induced in rats by social isolation plus resident-intruder. We analyzed the expression of hypothalamic GABAbR2 by Western blot and RT-PCR methods. Results The mRNA and protein expression levels of hypothalamic GABAbR2 in model rats were decreased when compared with that in the normal control group (P < 0.05-0.01), and the decrease of GABABR2 expression in anger-out model group was more significant than that in anger-in model group. Compared with the model groups, mRNA and protein expression levels of hypothalamic GABArR2 were increased in the medication groups to various degrees. Conclusion The decrease of hypothalamic GABAbR2 expression is one of common e- motional mechanisms in rats with with anger-out and anger-in emotion, and Jingqianping Granules and Jingqianshu Granules can up-regulate the GABAbR2 expression level.%目的 探索愤怒、郁怒情绪与γ氨基丁酸B2受体(GABABR2)的关系,以及调肝方药经前平颗粒和经前舒颗粒的中枢干预机制.方法采用居住入侵和社会隔离的方法复制愤怒、郁怒情绪大鼠模型,用RT-PCR和Western Blot的方法检测GABARR2 mRNA和蛋白的表达差异.结果与正常对照组相比,愤怒、郁怒情绪模型大鼠下丘脑GABABR2 mRNA水平和蛋白水平均明显下降(P<0.01~0.05),而且愤怒模型组的降低程度明显大于郁怒模型组.与各模型组相比,各给药组GABABR2 mRNA水平和蛋白水平均有不同程度的升高.结论大鼠下丘脑GABABR2表达降低可能是影响大鼠愤怒和郁怒情绪的重要共性机制之一;中药经前平和经前舒颗粒对GABABR2表达异常变化具有调节作用.

  4. 电针对雌性去势大鼠行为学和下丘脑室旁核c-fos表达的影响%Effect of electroacupuncture on behavioral and the expression of proto-oncogene c-fos in the hypothalamic paraventricular nucleus in female ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    申国明; 许浩; 胡光明; 尹刚; 王海颖; 刘艳

    2011-01-01

    目的:观察电针对雌性切除卵巢(去势)大鼠行为学、血浆雌二醇(E)及下丘脑室旁核c-fos表达的影响,探讨电针的抗抑郁效应及其机制.方法:SPF级SD雌性成年大鼠40只,随机分为正常对照组、去势组、电针组及美雌醇组.除正常对照组外大鼠均行双侧卵巢切除术.2周后,给予双侧内关、三阴交穴位电针干预处理2周.强迫游泳实验(FST)观察行为学变化;免疫组化观察下丘脑室旁核c-fos表达;放射免疫方法检测m浆E、FSH及LH变化.结果:大鼠卵巢切除4周后,FST显示不动时间明显增加(P水平降低(P水平明显升高(P<0.01),FSH(P<0.05,P<0.01)和LH(P<0.01,P<0.05)水平明显降低,室旁核c-fos阳性表达明娃增强.结论:去卵巢后,可致大鼠行为学改变,表现为抑郁倾向;电针干预具有明显抗抑郁效应,调整下丘脑轴是其可能机制.%Objective: To observe the effects of electroacupuncture (EA) on depression-like behavior, estradiol (E2) and the expression of proto-oncogene c-fos in the hypothalamic paraventricular nucleus (PVN) in ovariectomized (OVX) female rats. Methods: SPF grade SD female rats were ovariectomized. After two weeks recovery, the rats in APU group were treated by EA in bilateral Neiguan and Sanyinjiao for two weeks and the rats in E group were treated by mestranol. Later let ail the rats in every group to undergo FST. To measure the sum of time about immobility, struggling and swimming in the second FST (within 5 minutes), the levels of Ej, FSH, LH in blood serum were measured by Radioimmunoassay (RIA) and the expressions of proto-oncogene c-fos in PVN were ovserved by immunohistochemistry. Results: The time of immobility increased significantly in OVX group after rats were ovariectomized for 4 weeks (P<0.01), the levels of E, in blood plasma decreased (P<0.05), and the levels of FSH (P<0.01) and LH (P<0.05) increased significantly. After treated by EA, the levels of Ej increased significantly

  5. Facilitated thyrotropin release after retrochiasmatic hypothalamic knife cuts.

    Science.gov (United States)

    Phelps, C P; Colombo, J A

    1981-03-01

    Diencephalic structures that influence plasma thyrotropin (TSH) in male rats under pentobarbital anesthesia (35 mg/kg, IP) were studied by combining medial preoptic area-suprachiasmatic nucleus (MPOA-Sch) bilateral electrical stimulation (monophasic pulses, 200 microA at 50 Hz, 30 min) with progressive midline lesions produced by a retractable Halász knife. Plasma TSH was measured by radioimmunoassay just before (0 time) and at 30, 60 and 90 min after the beginning of stimulation. Rats that had received only sham surgical procedures 90 days prior to stimulation were characterized by a more than 2-3 fold elevation in basal (0 time) plasma TSH levels when compared to those found in intact control rats and expected elevations in plasma TSH at 30 min after stimulation were eliminated. After a small frontal cut (1.3 FC), 0 time plasma TSH levels increased more tha 4-fold above those of controls in association with a facilitation of stimulated release of TSH. When the knife blade radius was 1.5 mm (1.5 FC) the facilitation of TSH release after stimulation occurred again; however, 0 time plasma TSH concentrations in 1.5 FC rats were not different from control levels. These effects of midline cortical, thalamic and hypothalamic damage on TSH release required the passage of more than 12 days after brain surgery. Collectively, these findings suggest potential neural elements that are inhibitory for 'basal' and 'phasic' TSH release which are in close proximity to a separate excitatory neural system and which can be activated by MPOA-Sch stimulation.

  6. Galanin: a hypothalamic-hypophysiotropic hormone modulating reproductive functions.

    Science.gov (United States)

    López, F J; Merchenthaler, I; Ching, M; Wisniewski, M G; Negro-Vilar, A

    1991-01-01

    Galanin (GAL) is widely distributed in the peripheral and the central nervous systems. In the brain, the highest GAL concentrations are observed within the hypothalamus and, particularly, in nerve terminals of the median eminence. This location, as well as GAL actions on prolactin, growth hormone, luteinizing hormone (LH), and LH-releasing hormone (LHRH) secretion, suggest the possibility that GAL may act as a putative hypothalamic-hypophysiotropic hormone. To establish this, GAL and LHRH levels were measured in hypophyseal portal plasma samples using specific radioimmunoassays. Rat galanin (rGAL) concentrations in portal blood were approximately 7-fold higher than those observed in peripheral plasma in male and female (estrus, diestrus) rats, indicating an active secretory process of rGAL into the portal vasculature. Frequent (10 min) sampling revealed that rGAL and LHRH were secreted into the portal circulation in a pulsatile manner with a pulse frequency of one pulse per hour. Interestingly, both hormone series depicted a high degree of coincident episodes. In fact, the probability of random coincidence, calculated by the algorithm HYPERGEO, was less than 0.01. Moreover, the retrograde tracer Fluoro-Gold, when given systemically, was taken up by GAL neurons in the hypothalamus, including a subset of neurons expressing rGAL and LHRH, strengthening the notion of the existence of a GAL neuronal system connected to the hypophyseal portal circulation. These observations reinforce the concept that GAL regulates pituitary hormone secretion. To analyze this in further detail, the effects of rGAL on LH secretion were evaluated under basal and stimulated conditions. rGAL induced a small but dose-dependent increase in LH secretion from cultured, dispersed pituitary cells. Interestingly, rGAL enhanced the ability of LHRH to stimulate LH release. The tight link between GAL and LHRH neuronal systems is strengthened by the observation that during the estrous cycle of the rat

  7. ghrelin对糖尿病大鼠下丘脑弓状核胃牵张敏感神经元放电活动的影响%EFFECTS OF ghrelin ON DISCHARGE ACTIVITY OF GASTRIC DISTENTION NEURONS IN HYPOTHALAMIC ARCUATUS NUCLEUS OF DIABETIC RATS

    Institute of Scientific and Technical Information of China (English)

    侯滕菲; 徐珞

    2012-01-01

    Objective To observe the changes of activity of gastric distention (GD) sensitive neurons of hypothalamic arcuate nucleus (Arc) in rat models with diabetes mellitus (DM) , and to study the effects of ghrelin on GD neurons in hypothalamic arcuatus nucleus in the rats. Methods A rat model of DM was created by intraperitoneal injection of streptozotocin (STZ). The effects of ghrelin and [D-Lys-3]-GHRP-6 on GD sensitive neurons of Arc in DM rats were observed by recording extracellular potentials of single neurons. Results In normal rats, 98 GD sensitivity neurons were recorded in Arc of normal rats, in which, 64. 3% were classified as GD-excitatory (GD-E) neurons, and 35. 7% were GD-inhibitory (GD-I) neurons. Microinjection of ghrelin could excite 73. 0% of GD-E neurons, and discharge frequency significantly increased (t = 2. 01 ,P0. 05) , but ghrelin made neuronal excitation ratio of GD-E obviously reduce (x2 = 3. 86,P0. 05). Conclusion The ghrelin of hippocampus Arc involves in regulation of spontaneous discharge activity of GD sensitive neurons in diabetic rats, which is likely to be realized through ghrelin receptor.%目的 观察链脲佐菌素(STZ)所致糖尿病大鼠下丘脑弓状核(Arc)胃牵张(GD)敏感神经元放电活动改变,探讨ghrelin对糖尿病大鼠下丘脑Arc GD敏感神经元放电活动的影响及机制.方法 采用STZ腹腔注射诱导糖尿病大鼠模型.通过细胞外记录神经元单位放电方法,观察ghrelin及其受体阻断剂[D-Lys-3]-GHRP-6对糖尿病大鼠下丘脑Arc GD敏感神经元自发放电活动的影响.结果 在正常大鼠,Arc记录到的98个GD敏感神经元中,64.3%为GD兴奋性(GD-E)神经元,35.7%为GD抑制性(GD-I)神经元.Arc注射ghrelin可兴奋73.0%的GD-E神经元,其放电频率显著增加(t=2.01,P<0.05);Arc注射ghrelin可抑制60.0%的GD-I神经元,其放电频率显著降低(t=4.49,P<0.01);ghrelin改变GD神经元放电效应可被[D-Lys-3]-GHRP-6阻断.

  8. Effects of Chinese herbal medicines for regulating liver qi on expression of 5-hydroxytryptamine 3B receptor in hypothalamic tissues of rats with anger emotion%调肝方药对愤怒和郁怒情绪模型大鼠下丘脑5-羟色胺3B受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    葛庆芳; 张惠云

    2011-01-01

    Objective: To explore the central mechanisms of anger emotion and the effects of Chinese herbal medicines for regulating liver qi on the anger emotion and the expression level of 5-hydroxytryptamine 3B receptor (5-HT3BR) in rat hypothalamus.Methods: Rat models of anger-in or anger-out emotions were prepared by the methods of resident intruder paradigm. There were five groups in this study: control, anger-in model, Jingqianshu Granule-treated anger-in, anger-out model and Jingqianping Granule-treated anger-out groups. The treatment groups were orally given Jingqianshu granules and Jingqianping granules respectively, and the model groups and the normal control group were given sterile water. Open-field test and sucrose preference test were used to evaluate behavioristics of the rats. Semi-quantitative reverse transcription-polymerase chain reaction and Western blot methods were used to detect the expression levels of 5-HT3BR mRNA and protein in the rat hypothalamus. Results; The expression of 5-HT3BR in hypothalamus of anger-in model rats increased obviously (P<0.01) and that of anger-out model rats decreased obviously (P<0.01) compared with the normal control group. Compared with the model group, the expressions of 5-HT3BR in the treatment groups were significantly improved (P<0.01) after treatment, and recovered to normal level.Conclusion: The anger-in stimulation obviously increases hypothalamic 5-HT3BR expression and the anger-out emotion can obviously reduce its expression. Chinese herbal medicines for regulating liver qi may treat anger emotion in rats by improving the hypothalamic 5-HT3BR protein and gene expression levels.%目的:观察大鼠下丘脑5-羟色胺3B受体(5-hydroxytryptamine 3B receptor,5-HT3BR)表达的变化,探讨大鼠下丘脑5-HT3BR在愤怒和郁怒反应情绪发生机制中的作用,研究中药复方经前平颗粒和经前舒颗粒改善愤怒和郁怒情绪的中枢作用靶点.方法:采用居住入侵结合社会隔离的方法

  9. Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome

    Science.gov (United States)

    Gillard, Laura; Billiauws, Lore; Stan-Iuga, Bogdan; Ribeiro-Parenti, Lara; Jarry, Anne-Charlotte; Cavin, Jean-Baptiste; Cluzeaud, Françoise; Mayeur, Camille; Thomas, Muriel; Freund, Jean-Noël; Lacorte, Jean-Marc; Le Gall, Maude; Bado, André; Joly, Francisca; Le Beyec, Johanne

    2016-01-01

    Short bowel syndrome (SBS) patients developing hyperphagia have a better outcome. Gastrointestinal endocrine adaptations help to improve intestinal functions and food behaviour. We investigated neuroendocrine adaptations in SBS patients and rat models with jejuno-ileal (IR-JI) or jejuno-colonic (IR-JC) anastomosis with and without parenteral nutrition. Circulating levels of ghrelin, PYY, GLP-1, and GLP-2 were determined in SBS rat models and patients. Levels of mRNA for proglucagon, PYY and for hypothalamic neuropeptides were quantified by qRT-PCR in SBS rat models. Histology and immunostaining for Ki67, GLP-1 and PYY were performed in SBS rats. IR-JC rats, but not IR-JI, exhibited significantly higher crypt depths and number of Ki67-positive cells than sham. Fasting and/or postprandial plasma ghrelin and PYY concentrations were higher, or tend to be higher, in IR-JC rats and SBS-JC patients than in controls. Proglucagon and Pyy mRNA levels were significantly enhanced in IR-JC rats. Levels of mRNA coding hypothalamic orexigenic NPY and AgRP peptides were significantly higher in IR-JC than in sham rats. We demonstrate an increase of plasma ghrelin concentrations, major changes in hypothalamic neuropeptides levels and greater induction of PYY in SBS-JC rats and patients suggesting that jejuno-colonic continuity creates a peculiar environment promoting further gut-brain adaptations. PMID:27323884

  10. Early hypothalamic FTO overexpression in response to maternal obesity--potential contribution to postweaning hyperphagia.

    Directory of Open Access Journals (Sweden)

    Vanni Caruso

    Full Text Available BACKGROUND: Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs of the fat mass and obesity associated (FTO gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO. METHODS: Female Sprague Dawley rats were exposed to chow or high fat diet (HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1, some litters were adjusted to 3 pups (vs. 12 control to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured. RESULTS: At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05; body weight approached significance (P = 0.07. Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding. SIGNIFICANCE: Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to HFD suggesting upregulation of FTO may contribute to subsequent hyperphagia, in line with some human

  11. Hypothalamic effects of neonatal diet: reversible and only partially leptin dependent.

    Science.gov (United States)

    Sominsky, Luba; Ziko, Ilvana; Nguyen, Thai-Xinh; Quach, Julie; Spencer, Sarah J

    2017-07-01

    Early life diet influences metabolic programming, increasing the risk for long-lasting metabolic ill health. Neonatally overfed rats have an early increase in leptin that is maintained long term and is associated with a corresponding elevation in body weight. However, the immediate and long-term effects of neonatal overfeeding on hypothalamic anorexigenic pro-opiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP)/neuropeptide Y (NPY) circuitry, and if these are directly mediated by leptin, have not yet been examined. Here, we examined the effects of neonatal overfeeding on leptin-mediated development of hypothalamic POMC and AgRP/NPY neurons and whether these effects can be normalised by neonatal leptin antagonism in male Wistar rats. Neonatal overfeeding led to an acute (neonatal) resistance of hypothalamic neurons to exogenous leptin, but this leptin resistance was resolved by adulthood. While there were no effects of neonatal overfeeding on POMC immunoreactivity in neonates or adults, the neonatal overfeeding-induced early increase in arcuate nucleus (ARC) AgRP/NPY fibres was reversed by adulthood so that neonatally overfed adults had reduced NPY immunoreactivity in the ARC compared with controls, with no further differences in AgRP immunoreactivity. Short-term neonatal leptin antagonism did not reverse the excess body weight or hyperleptinaemia in the neonatally overfed, suggesting factors other than leptin may also contribute to the phenotype. Our findings show that changes in the availability of leptin during early life period influence the development of hypothalamic connectivity short term, but this is partly resolved by adulthood indicating an adaptation to the metabolic mal-programming effects of neonatal overfeeding. © 2017 Society for Endocrinology.

  12. Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex

    DEFF Research Database (Denmark)

    Gjedde, Albert; Geday, Jacob

    2009-01-01

    We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin......-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact...... of emotive images rated by the patients off the DBS. We then searched for sites in the brain that had significant correlation of the changes of blood flow with the emotional impact rated by the patients. The results indicate a significant link between the emotional impact when patients are not stimulated...

  13. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

    Science.gov (United States)

    Oyola, Mario G; Handa, Robert J

    2017-08-31

    Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

  14. A neuropsychological test of belief and doubt: Damage to ventromedial prefrontal cortex increases credulity for misleading advertising

    Directory of Open Access Journals (Sweden)

    Erik eAsp

    2012-07-01

    Full Text Available We have proposed the False Tagging Theory as a neurobiological model of belief and doubt processes. The theory posits that the prefrontal cortex is critical for normative doubt toward properly comprehended ideas or cognitions. Such doubt is important for advantageous decisions, for example in the financial and consumer purchasing realms. Here, using a neuropsychological approach, we put the False Tagging Theory to an empirical test, hypothesizing that focal damage to the ventromedial prefrontal cortex would cause a doubt deficit that would result in higher credulity and purchase intention for consumer products featured in misleading advertisements. We presented 8 consumer ads to 18 patients with focal brain damage to the ventromedial prefrontal cortex, 21 patients with focal brain damage outside the prefrontal cortex, and 10 demographically similar healthy comparison participants. Patients with ventromedial prefrontal cortex damage were (1 more credulous to misleading ads; and (2 showed the highest intention to purchase the products in the misleading advertisements, relative to patients with brain damage outside the prefrontal cortex and healthy comparison participants. The pattern of findings was obtained even for ads in which the misleading bent was corrected by a disclaimer. The evidence is consistent with our proposal that damage to the ventromedial prefrontal cortex disrupts a false tagging mechanism which normally produces doubt and skepticism for cognitive representations. We suggest that the disruption increases credulity for misleading information, even when the misleading information is corrected for by a disclaimer. This mechanism could help explain poor financial decision-making when persons with ventromedial prefrontal dysfunction (e.g., caused by neurological injury or aging are exposed to persuasive information.

  15. 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'.

  16. Hypothalamic-endocrine aspects in Huntington's disease.

    Science.gov (United States)

    Petersén, Asa; Björkqvist, Maria

    2006-08-01

    Huntington's disease (HD) is a hereditary and fatal disorder caused by an expanded CAG triplet repeat in the HD gene, resulting in a mutant form of the protein huntingtin. Wild-type and mutant huntingtin are expressed in most tissues of the body but the normal function of huntingtin is not fully known. In HD, the neuropathology is characterized by intranuclear and cytoplasmic inclusions of huntingtin aggregates, and cell death primarily in striatum and cerebral cortex. However, hypothalamic atrophy occurs at early stages of HD with loss of orexin- and somatostatin-containing cell populations. Several symptoms of HD such as sleep disturbances, alterations in circadian rhythm, and weight loss may be due to hypothalamic dysfunction. Endocrine changes including increased cortisol levels, reduced testosterone levels and increased prevalence of diabetes are found in HD patients. In HD mice, alterations in the hypothalamic-pituitary-adrenal axis occurs as well as pancreatic beta-cell and adipocyte dysfunction. Increasing evidence points towards important pathology of the hypothalamus and the endocrine system in HD. As many neuroendocrine factors are secreted into the cerebrospinal fluid, blood and urine, it is possible that their levels may reflect the disease state in the central nervous system. Investigating neuroendocrine changes in HD opens up the possibility of finding biomarkers to evaluate future therapies for HD, as well as of identifying novel targets for therapeutic interventions.

  17. Effects of hypothalamic neurodegeneration on energy balance.

    Directory of Open Access Journals (Sweden)

    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.

  18. Leptin signalling pathways in hypothalamic neurons.

    Science.gov (United States)

    Kwon, Obin; Kim, Ki Woo; Kim, Min-Seon

    2016-04-01

    Leptin is the most critical hormone in the homeostatic regulation of energy balance among those so far discovered. Leptin primarily acts on the neurons of the mediobasal part of hypothalamus to regulate food intake, thermogenesis, and the blood glucose level. In the hypothalamic neurons, leptin binding to the long form leptin receptors on the plasma membrane initiates multiple signaling cascades. The signaling pathways known to mediate the actions of leptin include JAK-STAT signaling, PI3K-Akt-FoxO1 signaling, SHP2-ERK signaling, AMPK signaling, and mTOR-S6K signaling. Recent evidence suggests that leptin signaling in hypothalamic neurons is also linked to primary cilia function. On the other hand, signaling molecules/pathways mitigating leptin actions in hypothalamic neurons have been extensively investigated in an effort to treat leptin resistance observed in obesity. These include SOCS3, tyrosine phosphatase PTP1B, and inflammatory signaling pathways such as IKK-NFκB and JNK signaling, and ER stress-mitochondrial signaling. In this review, we discuss leptin signaling pathways in the hypothalamus, with a particular focus on the most recently discovered pathways.

  19. In vivo occupancy of female rat brain estrogen receptors by 17beta-estradiol and tamoxifen.

    Science.gov (United States)

    Pareto, D; Alvarado, M; Hanrahan, S M; Biegon, A

    2004-11-01

    Estrogens or antiestrogens are currently used by millions of women, but the interaction of these hormonal agents with brain estrogen receptors (ER) in vivo has not been characterized to date. Our goal was to assess, in vivo, the extent and regional distribution of brain ER occupancy in rats chronically exposed to 17beta-estradiol (E(2)) or tamoxifen (TAM). For that purpose, female ovariectomized Sprague-Dawley rats were implanted with subcutaneous pellets containing either placebo (OVX), E(2), or TAM for 3 weeks. ER occupancy in grossly dissected regions was quantified with 16alpha-[(18)F]fluoroestradiol ([(18)F]FES). Both E(2) and TAM produced significant decreases in radioligand uptake in the brain although the effect of E(2) was larger and more widespread than the effect of TAM. Detailed regional analysis of the interaction was then undertaken using a radioiodinated ligand, 11beta-methoxy-16alpha-[(125)I]iodo-estradiol ([(125)I]MIE(2)), and quantitative ex vivo autoradiography. E(2) treatment resulted in near-complete (86.6 +/- 17.5%) inhibition of radioligand accumulation throughout the brain, while ER occupancy in the TAM group showed a marked regional distribution such that percentage inhibition ranged from 40.5 +/- 15.6 in the ventrolateral part of the ventromedial hypothalamic nucleus to 84.6 +/- 4.5 in the cortical amygdala. These results show that exposure to pharmacologically relevant levels of TAM produces a variable, region-specific pattern of brain ER occupancy, which may be influenced by the regional proportion of ER receptor subtypes. These findings may partially explain the highly variable and region-specific effects observed in neurochemical, metabolic, and functional studies of the effects of TAM in the brain of experimental animals as well as human subjects.

  20. Binge Drinking Induces Whole-Body Insulin Resistance by Impairing Hypothalamic Insulin Action

    Science.gov (United States)

    Lindtner, Claudia; Scherer, Thomas; Zielinski, Elizabeth; Filatova, Nika; Fasshauer, Martin; Tonks, Nicholas K.; Puchowicz, Michelle; Buettner, Christoph

    2013-01-01

    Individuals with a history of binge drinking have an increased risk of developing the metabolic syndrome and type 2 diabetes. Whether binge drinking impairs glucose homeostasis and insulin action is unknown. To test this, we treated Sprague-Dawley rats daily with alcohol (3 g/kg) for three consecutive days to simulate human binge drinking and found that these rats developed and exhibited insulin resistance even after blood alcohol concentrations had become undetectable. The animals were resistant to insulin for up to 54 hours after the last dose of ethanol, chiefly a result of impaired hepatic and adipose tissue insulin action. Because insulin regulates hepatic glucose production and white adipose tissue lipolysis, in part through signaling in the central nervous system, we tested whether binge drinking impaired brain control of nutrient partitioning. Rats that had consumed alcohol exhibited impaired hypothalamic insulin action, defined as the ability of insulin infused into the mediobasal hypothalamus to suppress hepatic glucose production and white adipose tissue lipolysis. Insulin signaling in the hypothalamus, as assessed by insulin receptor and AKT phosphorylation, decreased after binge drinking. Quantitative polymerase chain reaction showed increased hypothalamic inflammation and expression of protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling. Intracerebroventricular infusion of CPT-157633, a small-molecule inhibitor of PTP1B, prevented binge drinking–induced glucose intolerance. These results show that, in rats, binge drinking induces systemic insulin resistance by impairing hypothalamic insulin action and that this effect can be prevented by inhibition of brain PTP1B. PMID:23363978

  1. 白芍提取物对嗅球损毁抑郁模型大鼠行为学及下丘脑-垂体-肾上腺轴的影响%Influences of Extract of Peony Radix Alba on Behavior and Hypothalamic-pituitary-adrenocortical Axis in Depressive Rats Model with Damaged Olfactory Bulb

    Institute of Scientific and Technical Information of China (English)

    王景霞; 张建军; 苗春平; 刘妍; 林清; 陈振振

    2011-01-01

    Objective: To investigate the influences of extract from Peony Radix Alba on the behavioral and hypothalamic-pituitary-adrenocortical (HPA) axis changes in rats with damaged olfactory bulb (DOB). Method: The tests of open-field and step-down passive avoidance were used to observe the behaviors of rats.Radioimmunoassay (RIA) was used to analyze the level of corticotropin releasing hormone (CRH) in hypothalamus, adrenocorticotropic hormone (ACTH) in pituitary gland and cortisol (CORT) in serum of rats with DOB. Result: The rats had a characteristic hyperactivity in the test of "open-field" and learning deficits in stepdown passive avoidance ( P < 0. 05 ), and their levels of CRH, ACTH and CORT increased significantly ( P < 0. 05). The extract of Peony Radix Alba at the dose of 70,35 mg·kg-1 corrected the behavioral changes (P < 0. 05 ) and decreased the levels of CRH, ACTH and CORT ( P < 0. 05). Conclusion: The extract of Peony Radix Alba can correct behavioral changes in rats with DOB, and its regulating effect on HPA axis is one of the mechanisms for treating depression.%目的:研究白芍提取物对嗅球损毁抑郁模型大鼠行为学及下丘脑一垂体.肾上腺(HPA)轴的影响.方法:将嗅球损毁大鼠随机分为对照组、模型组、阳性药氟西汀2.5 mg·kg-1组以及白芍提取物70,35,17.5 mg·kg-1组,采用敞箱法、跳台法观察嗅球损毁大鼠的行为变化,间时用放免法分析白芍提取物对嗅球损毁大鼠下丘脑促肾上腺皮质激素释放素(CRH)、垂体促肾上腺皮质激素(ACTH)和血清皮质酮(CORT)含量的影响.结果:大鼠嗅球损毁后敞箱行为出现明显变化,水平运动和垂直运动显著增加,白芍提取物中、高剂量组可显著降低大鼠水平运动和垂直运动的得分;跳台试验中,造模后大鼠训练期和测试期的错误次数显著增加,自芍提取物中、高剂量组能显著降低嗅球损毁大鼠训练期和测试期的触电次数;嗅球损毁大

  2. Insulin Detemir Causes Lesser Weight Gain in Comparison to Insulin Glargine: Role on Hypothalamic NPY and Galanin

    Directory of Open Access Journals (Sweden)

    Mohammad Ishraq Zafar

    2014-01-01

    Full Text Available Objective. Compared with other insulin analogues, insulin detemir induces less weight gain. This study investigated whether this effect was achieved by influencing the hypothalamic appetite regulators neuropeptide Y (NPY and galanin (GAL. Methods. Type  2 diabetic rat models were established with a high-fat diet and intraperitoneal injection of STZ. All rats were divided into NC, DM, DM+DE and DM+GLA groups. Glycemic levels of all study groups were checked at study onset and after 4 weeks of insulin treatment. Food intake and body weight were monitored during treatment. After 4 weeks, the hypothalamus of rats was examined for NPY and GAL mRNA and protein expression. Results. After 4 weeks of treatment, compared with the DM+GLA group, the DM+DE group exhibited less food intake (P<0.05 and less weight gain (P<0.05, but showed similar glycemic control. The expression of hypothalamic NPY and GAL at both mRNA and protein level were significantly lower (P<0.05 in the DM+DE group. Conclusion. Insulin detemir decreased food intake in type 2 diabetic rats, which led to reduced weight gain when compared to insulin glargine treatment. This effect is likely due to downregulation of hypothalamic NPY and GAL.

  3. Hypothalamic inflammation: a double-edged sword to nutritional diseases

    OpenAIRE

    Cai, Dongsheng; Liu, Tiewen

    2011-01-01

    The hypothalamus is one of the master regulators of various physiological processes, including energy balance and nutrient metabolism. These regulatory functions are mediated by discrete hypothalamic regions that integrate metabolic sensing with neuroendocrine and neural controls of systemic physiology. Neurons and non-neuronal cells in these hypothalamic regions act supportively to execute metabolic regulations. Under conditions of brain and hypothalamic inflammation, which may result from o...

  4. Increased hypothalamic serotonin turnover in inflammation-induced anorexia

    OpenAIRE

    Dwarkasing, J.T.; Witkamp, R F; Boekschoten, M.V.; Laak, ter, H.J.; Heins, M.S.; Norren, van, K.

    2016-01-01

    Background Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS....

  5. A subset of μ-opioid receptor-expressing cells in the rostral ventromedial medulla contribute to thermal hyperalgesia in experimental neuropathic pain.

    Science.gov (United States)

    Mase, Hiroshi; Sakai, Atsushi; Sakamoto, Atsuhiro; Suzuki, Hidenori

    2011-05-01

    The rostral ventromedial medulla (RVM) is a major region for the descending modulation of pain at the spinal cord level, and neurons in the RVM have been implicated in the inhibition and facilitation of spinal nociceptive transmission. Although recent studies have established that the RVM facilitation of nociceptive transmission in the spinal cord contributes to neuropathic pain, the underlying mechanisms remain largely unknown. In the present study, we investigated the effects of kainic acid (KA)-induced RVM damage on neuropathic pain behavior and the expression of molecules implicated in pain modulation. KA was injected into the RVM midline region after neuropathic pain was established by chronic constrictive injury of the left sciatic nerve. Thermal hyperalgesia, but not mechanical allodynia, was persistently suppressed in the ipsilateral paw by a single KA injection into the RVM for at least the next 7 days in a rat neuropathic pain model. KA injection alone did not affect the nocifensive responses to mechanical and thermal stimuli on the intact side. Immunohistochemical analysis revealed that KA injection into the RVM significantly reduced the number of immunoreactive neurons for μ-opioid receptors, but not tryptophan hydroxylase, in association with the analgesic effect. These results suggest that a subset of RVM neurons expressing μ-opioid receptors contribute to the maintenance of thermal hyperalgesia in neuropathic pain.

  6. 人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响%Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    刘丽琴; 罗艳; 张瑞睿; 郭建友

    2011-01-01

    Gingseng is commonly used in traditional Chinese medicine community for the treatment of depression-like dis, orders. Ginsenosides is considered to be the major active components of ginseng. Previous studies have demonstrated that ginsenosides produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether ginsenosides could affect the chronic unpredictable mild stress (CUMS)-induced depression in rats. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticesterone level, glucocorticoid receptor ( GR), mineralocorticoid receptor (MR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in rats exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated rats. Daily intragastric administration of ginsenosides (12. 5, 25, 50 mg · kg-1) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. However, there was no significant difference in MR mRNA level among groups. The results suggest that the antidepressant-like action of ginsenosides is likely mediated by modulating the function of hypothalamic- pituitary -adrenal axis and increasing the expression of BDNF in brain tissues.%目的:探讨人参皂苷对慢性应激所致大鼠抑郁模型的干预作用.方法:通过测定大鼠血清中皮质酮(COR)、糖皮质激素受体(GR)、盐皮质激素受体(MR)和脑组织中神经营养(BDNF)的mRNA表达水平,探讨人参皂苷的抗抑郁机制.结果:与正常组大鼠比较,经过慢性应激6周后大鼠糖水偏好显著下降,强迫游泳测试不动时间

  7. 芍药内酯苷对嗅球切除抑郁模型大鼠行为学以及下丘脑-垂体-肾上腺轴功能的影响%Effect of albiflorin on behavior and hypothalamic-pituitary-adrenocortical axis in olfactory bulbectomized rats

    Institute of Scientific and Technical Information of China (English)

    陈岚; 龚正华; 薛瑞; 张亭亭; 李云峰; 洪浩; 张有志

    2014-01-01

    目的:探讨芍药内酯苷(Alb)的抗抑郁作用及其对下丘脑-垂体-肾上腺轴(HPA)功能的影响。方法采用切除大鼠嗅球制备抑郁模型,恢复14 d后每天2次给予盐酸丙咪嗪(IMI)5.0 mg·kg -1,Alb 2.5,5.0和10.0 mg·kg -1,连续给药14 d。开场实验检测大鼠的酶联免疫法检测血清中皮质酮(CO RT)及促肾上腺皮质激素(ACTH)含量;Western蛋白质印迹法检测海马糖皮质激素受体(GR)表达水平。结果与假手术组相比,嗅球切除模型组大鼠运动距离、运动时间和运动速度均显著增加(P<0.01);给药7 d 后,Alb 10.0 mg·kg -1显著降低嗅球切除大鼠运动时间、速度和距离(P<0.05);给药14 d 后,Alb 5.0和10.0 mg·kg -1均可以显著降低嗅球切除大鼠运动时间、速度和距离(P<0.05)。嗅球切除模型组大鼠血清CORT和ACTH 水平显著升高(P<0.01),海马 GR 表达下降(P<0.01),给予 Alb 2.5,5.0和10.0 mg·kg -1可显著降低嗅球切除大鼠血清CORT和ACTH水平(P<0.05);Western蛋白质印迹法结果表明,Alb 5.0和10.0 mg·kg -1可增加海马GR的表达(P<0.05)。结论芍药内酯苷对嗅球切除模型大鼠具有明确的抗抑郁行为效应,其抗抑郁作用机制可能与抑制H PA功能亢进有关。%OBJECTIVE Toexploretheantidepressanteffectsofalbiflorinandtheinvolvementof hypothalamic-pituitary-adrenocortical (HPA) axis function in its antidepressant potency.METHODS Two weeks after the olfactory bulbectomized (OB)surgery,albiflorin (2.5 ,5.0 ,10.0 mg·kg -1 ,ig) and imipramine 5.0 mg·kg -1 (ig)were given to rats twice a day for 14 d.The open-field test was con-ducted to evaluate the move ment distance,move ment ti me and velocity of olfactory bulbecto mized rats and sham-operated rats.The serum levels of corticosterone(CORT)and adrenocorticotropic hormone (ACTH)in rats were measured by the

  8. Cocaine- and amphetamine-regulated transcript is present in hypothalamic neuroendocrine neurones and is released to the hypothalamic-pituitary portal circuit

    DEFF Research Database (Denmark)

    Larsen, P J; Seier, V; Fink-Jensen, A

    2003-01-01

    -opiomelanocortin in the ventrolateral part, but completely absent from neuroendocrine neurones of the dorsomedial part. To assess the possible role of CART as a hypothalamic-releasing factor, immunoreactive CART was measured in blood samples from the long portal vessels connecting the median eminence with the anterior pituitary gland....... Adult male rats were anaesthetized and the infundibular stalk exposed via a transpharyngeal approach. The long portal vessels were transected and blood collected in 30-min periods (one prestimulatory and three poststimulatory periods). Compared to systemic venous plasma samples, baseline concentrations...... of immunoreactive CART were elevated in portal plasma. Exposure to sodium nitroprusside hypotension triggered a two-fold elevation of portal CART42-89 immunoreactivity throughout the 90-min stimulation period. In contrast, the concentration of portal plasma CART immunoreactivity dropped in the vehicle infused rats...

  9. Brain Ciliary Neurotrophic Factor (CNTF and hypothalamic control of energy homeostasis

    Directory of Open Access Journals (Sweden)

    Vacher Claire-Marie

    2011-09-01

    Full Text Available Cytokines play an important role in energy-balance regulation. Notably leptin, an adipocyte-secreted cytokine, regulates the activity of hypothalamic neurons that are involved in the modulation of appetite. Leptin decreases appetite and stimulates weight loss in rodents. Unfortunately, numerous forms of obesity in humans seem to be resistant to leptin action. The ciliary neurotrophic factor (CNTF is a neurocytokine that belongs to the same family as leptin and that was originally characterized as a neurotrophic factor that promotes the survival of a broad spectrum of neuronal cell types and that enhances neurogenesis in adult rodents. It presents the advantage of stimulating weight loss in humans, despite the leptin resistance. Moreover, the weight loss persists several weeks after the cessation of treatment. Hence, CNTF has been considered as a promising therapeutic tool for the treatment of obesity and has prompted intense research aimed at identifying the cellular and molecular mechanisms underlying its potent anorexigenic properties. It has been found that CNTF shares signaling pathways with leptin and is expressed in the arcuate nucleus (ARC, a key hypothalamic region controlling food intake. Endogenous CNTF may also participate in the control of energy balance. Indeed, its expression in the ARC is inversely correlated to body weight in rats fed a high-sucrose diet. Thus hypothalamic CNTF may act, in some individuals, as a protective factor against weight gain during hypercaloric diet and could account for individual differences in the susceptibility to obesity.

  10. Hypothalamic S1P/S1PR1 axis controls energy homeostasis in Middle-Aged Rodents: the reversal effects of physical exercise

    Science.gov (United States)

    Silva, Vagner Ramon Rodrigues; Katashima, Carlos Kiyoshi; Bueno Silva, Carla G.; Lenhare, Luciene; Micheletti, Thayana Oliveira; Camargo, Rafael Ludemann; Ghezzi, Ana Carolina; Camargo, Juliana Alves; Assis, Alexandre Moura; Tobar, Natalia; Morari, Joseane; Razolli, Daniela S.; Moura, Leandro Pereira; Pauli, José Rodrigo; Cintra, Dennys Esper; Velloso, Lício Augusto; Saad, Mario J.A; Ropelle, Eduardo Rochete

    2017-01-01

    Recently, we demonstrated that the hypothalamic S1PR1/STAT3 axis plays a critical role in the control of food consumption and energy expenditure in rodents. Here, we found that reduction of hypothalamic S1PR1 expression occurs in an age-dependent manner, and was associated with defective thermogenic signaling and weight gain. To address the physiological relevance of these findings, we investigated the effects of chronic and acute exercise on the hypothalamic S1PR1/STAT3 axis. Chronic exercise increased S1PR1 expression and STAT3 phosphorylation in the hypothalamus, restoring the anorexigenic and thermogenic signals in middle-aged mice. Acutely, exercise increased sphingosine-1-phosphate (S1P) levels in the cerebrospinal fluid (CSF) of young rats, whereas the administration of CSF from exercised young rats into the hypothalamus of middle-aged rats at rest was sufficient to reduce the food intake. Finally, the intracerebroventricular (ICV) administration of S1PR1 activators, including the bioactive lipid molecule S1P, and pharmacological S1PR1 activator, SEW2871, induced a potent STAT3 phosphorylation and anorexigenic response in middle-aged rats. Overall, these results suggest that hypothalamic S1PR1 is important for the maintenance of energy balance and provide new insights into the mechanism by which exercise controls the anorexigenic and thermogenic signals in the central nervous system during the aging process. PMID:28039439

  11. Involvement of hypothalamic AMP-activated protein kinase in leptin-induced sympathetic nerve activation.

    Directory of Open Access Journals (Sweden)

    Mamoru Tanida

    Full Text Available In mammals, leptin released from the white adipose tissue acts on the central nervous system to control feeding behavior, cardiovascular function, and energy metabolism. Central leptin activates sympathetic nerves that innervate the kidney, adipose tissue, and some abdominal organs in rats. AMP-activated protein kinase (AMPK is essential in the intracellular signaling pathway involving the activation of leptin receptors (ObRb. We investigated the potential of AMPKα2 in the sympathetic effects of leptin using in vivo siRNA injection to knockdown AMPKα2 in rats, to produce reduced hypothalamic AMPKα2 expression. Leptin effects on body weight, food intake, and blood FFA levels were eliminated in AMPKα2 siRNA-treated rats. Leptin-evoked enhancements of the sympathetic nerve outflows to the kidney, brown and white adipose tissues were attenuated in AMPKα2 siRNA-treated rats. To check whether AMPKα2 was specific to sympathetic changes induced by leptin, we examined the effects of injecting MT-II, a melanocortin-3 and -4 receptor agonist, on the sympathetic nerve outflows to the kidney and adipose tissue. MT-II-induced sympatho-excitation in the kidney was unchanged in AMPKα2 siRNA-treated rats. However, responses of neural activities involving adipose tissue to MT-II were attenuated in AMPKα2 siRNA-treated rats. These results suggest that hypothalamic AMPKα2 is involved not only in appetite and body weight regulation but also in the regulation of sympathetic nerve discharges to the kidney and adipose tissue. Thus, AMPK might function not only as an energy sensor, but as a key molecule in the cardiovascular, thermogenic, and lipolytic effects of leptin through the sympathetic nervous system.

  12. Involvement of hypothalamic AMP-activated protein kinase in leptin-induced sympathetic nerve activation.

    Science.gov (United States)

    Tanida, Mamoru; Yamamoto, Naoki; Shibamoto, Toshishige; Rahmouni, Kamal

    2013-01-01

    In mammals, leptin released from the white adipose tissue acts on the central nervous system to control feeding behavior, cardiovascular function, and energy metabolism. Central leptin activates sympathetic nerves that innervate the kidney, adipose tissue, and some abdominal organs in rats. AMP-activated protein kinase (AMPK) is essential in the intracellular signaling pathway involving the activation of leptin receptors (ObRb). We investigated the potential of AMPKα2 in the sympathetic effects of leptin using in vivo siRNA injection to knockdown AMPKα2 in rats, to produce reduced hypothalamic AMPKα2 expression. Leptin effects on body weight, food intake, and blood FFA levels were eliminated in AMPKα2 siRNA-treated rats. Leptin-evoked enhancements of the sympathetic nerve outflows to the kidney, brown and white adipose tissues were attenuated in AMPKα2 siRNA-treated rats. To check whether AMPKα2 was specific to sympathetic changes induced by leptin, we examined the effects of injecting MT-II, a melanocortin-3 and -4 receptor agonist, on the sympathetic nerve outflows to the kidney and adipose tissue. MT-II-induced sympatho-excitation in the kidney was unchanged in AMPKα2 siRNA-treated rats. However, responses of neural activities involving adipose tissue to MT-II were attenuated in AMPKα2 siRNA-treated rats. These results suggest that hypothalamic AMPKα2 is involved not only in appetite and body weight regulation but also in the regulation of sympathetic nerve discharges to the kidney and adipose tissue. Thus, AMPK might function not only as an energy sensor, but as a key molecule in the cardiovascular, thermogenic, and lipolytic effects of leptin through the sympathetic nervous system.

  13. Forebrain patterns of c-Fos and FosB induction during cancer-associated anorexia-cachexia in rat.

    Science.gov (United States)

    Konsman, Jan Pieter; Blomqvist, Anders

    2005-05-01

    Forebrain structures are necessary for the initiation of food intake and its coupling to energy expenditure. The cancer-related anorexia-cachexia syndrome is typified by a prolonged increase in metabolic rate resulting in body weight loss which, paradoxically, is accompanied by reduced food intake. The aim of the present work was to study the forebrain expression of Fos proteins as activation markers and thus to identify potential neurobiological mechanisms favouring catabolic processes or modulating food intake in rats suffering from cancer-related anorexia-cachexia. Neurons in forebrain structures showing most pronounced induction of Fos proteins were further identified neurochemically. To provoke anorexia-cachexia, cultured Morris hepatoma 7777 cells were injected subcutaneously in Buffalo rats. This resulted in a slowly growing tumour inducing approximately 7% body weight loss and a 20% reduction in food intake when the tumour represented 1-2% of body mass. Anorexia-cachexia in these animals was found to be accompanied by Fos induction in several hypothalamic nuclei including the paraventricular and ventromedial hypothalamus, in the parastrial nucleus, the amygdala, the bed nucleus of the stria terminalis, ventral striatal structures and the piriform and somatosensory cortices. Neurochemical identification revealed that the vast majority of FosB-positive neurons in the nucleus accumbens, ventral caudate-putamen and other ventral striatal structures contained prodynorphin or proenkephalin mRNA. These findings indicate that forebrain structures that are part of neuronal networks modulating catabolic pathways and food ingestion are activated during tumour-associated anorexia-cachexia and may contribute to the lack of compensatory eating in response to weight loss characterizing this syndrome.

  14. Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression.

    Science.gov (United States)

    Joshi, R N; Safadi, F F; Barbe, M F; Del Carpio-Cano, Fe; Popoff, S N; Yingling, V R

    2011-10-01

    Hypothalamic amenorrhea and energy restriction during puberty affect peak bone mass accrual. One hypothesis suggests energy restriction alters hypothalamic function resulting in suppressed estradiol levels leading to bone loss. However, both positive and negative results have been reported regarding energy restriction and bone strength. Therefore, the purpose of this study was to investigate energy restriction and hypothalamic suppression during pubertal onset on bone mechanical strength and the osteogenic capacity of bone marrow-derived cells in two models: female rats treated with gonadotropin releasing hormone antagonists (GnRH-a) or 30% energy restriction. At 23 days of age, female Sprague Dawley rats were assigned to three groups: control group (C, n=10), GnRH-a group (n=10), and Energy Restriction (ER, n=12) group. GnRH-a animals received daily injections for 27 days. The animals in the ER group received 70% of the control animals' intake. After sacrifice (50 days of age), body weight, uterine and muscle weights were measured. Bone marrow-derived stromal cells were cultured and assayed for proliferation and differentiation into osteoblasts. Outcome measures included bone strength, bone histomorphometry and architecture, serum IGF-1 and osteocalcin. GnRH-a suppressed uterine weight, decreased osteoblast proliferation, bone strength, trabecular bone volume and architecture compared to control. Elevated serum IGF-1 and osteocalcin levels and body weight were found. The ER model had an increase in osteoblast proliferation compared to the GnRH-a group, similar bone strength relative to body weight and increased trabecular bone volume in the lumbar spine compared to control. The ER animals were smaller but had developed bone strength sufficient for their size. In contrast, suppressed estradiol via hypothalamic suppression resulted in bone strength deficits and trabecular bone volume loss. In summary, our results support the hypothesis that during periods of

  15. Effects of Electro-acupuncture on Insulin Resistance and Hypothalamic Agouti Gene-related Protein and Neuropeptide Y in Obesity Rats%电针对单纯性肥胖大鼠胰岛素抵抗及下丘脑刺鼠基因相关蛋白、神经肽Y的影响

    Institute of Scientific and Technical Information of China (English)

    刘霞; 何军锋; 屈娅婷; 刘志君; 蒲庆阳; 郭胜童; 杜佳; 蒋鹏飞

    2016-01-01

    目的:观察电针对饮食诱导的单纯性肥胖大鼠体质量、胰岛素抵抗及下丘脑刺鼠基因相关蛋白(AGRP)、神经肽Y(NPY)基因表达的影响,探讨电针治疗肥胖症的相关机制。方法50只SD雄性大鼠随机分为低脂组10只和高脂组40只,高脂组大鼠造模成功后,随机分为模型组、电针组、西药组,每组10只。电针组电针“后三里”和“曲池”,每日1次,每次20 min,连续28 d;西药组予奥利司他灌胃,低脂组和模型组不做治疗。每日记录大鼠体质量,检测空腹血糖和胰岛素,RT-qPCR检测下丘脑AGRP和NPY基因表达水平,HE染色观察脂肪组织和肝脏形态。结果治疗后电针组和西药组体质量、胰岛素抵抗指数、AGRP、NPY、脂肪细胞直径均低于模型组(P<0.05),2组比较差异无统计学意义。电针组和西药组肝脏脂变情况均得到改善。结论电针通过改善胰岛素抵抗,抑制NPY和AGRP神经元的表达,达到控制体质量增长的目的。%Objective To observe the effects of electro-acupuncture (EA) on body weight, insulin resistance, hypothalamic agouti gene-related protein (AGRP) and neuropeptide Y (NPY) in diet induced obesity (DIO) rats; To discuss its mechanism for DIO.Methods Fifty SD male rats were randomly divided into low fat diet groups (LFD) and high fat diet group. After the DIO models were established, the successful model rats were randomly divided into model group, EA group and Orlistat (OLST) group. EA was applied to “Zusanli” (ST36) and “Quchi” (LI11) for 20 minutes. The treatment was done once a day for 28 days. OLST was treated with orlistat by gavage. LFD and model did not receive treatment. Body weight was recorded every day. FPG and FINS were detected. The expressions of AGRP and NPY were detected by RT-QPCR. Morphological changes of adipocyte and liver were examined by HE staining.Results The body weight, HOMA-IR, AGRP, NPY and

  16. SPINAL CORD MECHANISMS MEDIATING BEHAVIORAL HYPERALGESIA INDUCED BY NEUROKININ-1 TACHYKININ RECEPTOR ACTIVATION IN THE ROSTRAL VENTROMEDIAL MEDULLA

    OpenAIRE

    Lagraize, S. C.; Guo, W; Yang, K.; Wei, F.; Ren, K; Dubner, R.

    2010-01-01

    Hyperalgesia in animal injury models is linked to activation of descending raphespinal modulatory circuits originating in the rostral ventromedial medulla (RVM). A neurokinin-1 (NK-1) receptor antagonist microinjected into the RVM before or after inflammation produced by complete Freund’s adjuvant (CFA) resulted in an attenuation of thermal hyperalgesia. A transient (acute) or a continuous infusion of Substance P (SP) microinjected into the RVM of non-inflamed animals led to similar pain hype...

  17. Giant solid-cystic hypothalamic hamartoma. Case report.

    Science.gov (United States)

    Dorfer, Christian; Kasprian, Gregor; Mühlebner, Angelika; Czech, Thomas

    2011-02-01

    Hypothalamic hamartomas are rare lesions for which different classification schemes have been proposed. The authors report on an exceptionally large solid-cystic hamartoma that led to hydrocephalus, precocious puberty, and intractable gelastic seizures. They discuss potential mechanisms of the development of hypothalamic hamartomas.

  18. Direct Cellular Peptidomics of Hypothalamic Neurons

    Science.gov (United States)

    Mitchell, Jennifer W.; Atkins, Norman; Sweedler, Jonathan V.; Gillette, Martha U.

    2011-01-01

    The chemical complexity of cell-to-cell communication has emerged as a fundamental challenge to understanding brain systems. This is certainly true for the hypothalamus, where neuropeptide signals are heterogeneous, localized and dynamic. Thus far, most hypothalamic peptidomic studies have centered on the entire structure; however, recent advances in collection strategies and analytical technologies have enabled direct, high-resolution peptidomic profiles focused on two regions of interest, the suprachiasmatic and supraoptic nuclei, including their subregions and individual cells. Suites of peptides now can be identified and probed for function. High spatial and analytical sensitivities reveal that discrete hypothalamic nuclei have distinct peptidomic signatures. Peptidomic discovery not only reveals unanticipated complexity, but also peptides previously unknown that act as key circuit components. Analysis of tissue releasates identifies peptides secreted into the extracellular environment and available for transmitting intercellular signals. Direct sampling techniques define peptide-releasate profiles in spatial, temporal and event-dependent patterns. These approaches are providing remarkable new insights into the complexity of neuropeptidergic cell-to-cell signaling central to neuroendocrine physiology. PMID:21334363

  19. 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.

  20. Differential activation of the ventromedial prefrontal cortex between male and female givers of social reputation.

    Science.gov (United States)

    Kawasaki, Iori; Ito, Ayahito; Fujii, Toshikatsu; Ueno, Aya; Yoshida, Kazuki; Sakai, Shinya; Mugikura, Shunji; Takahashi, Shoki; Mori, Etsuro

    2016-02-01

    Accumulating evidence has shown the profound influence of social reputation on human behavior and has implicated the ventromedial prefrontal cortex (vmPFC) in representing subjective values induced by social interaction. However, little is known regarding how the vmPFC encodes subjective pleasantness induced by social reputation received from others. We used functional magnetic resonance imaging (fMRI) to investigate how the vmPFC in males and females encodes the subjective pleasantness of social reputation received from the same gender and from the opposite gender. Behavioral data showed that positive reputation was perceived to be more pleasant than negative reputation. Intriguingly, both male and female subjects showed greater differences in the pleasantness scores between the positive reputation condition and the negative reputation condition from females than between positive and negative reputations from males. Imaging data revealed that the left vmPFC specifically contributed to the processing of positive reputation. The activity patterns of the vmPFC corresponded to the gender differences in behavior during the processing of social reputation. These results indicate that the vmPFC plays a role in representing the subjective value of positive social reputation and that this region might be a final computational site in a stream of value-based decision-making processes.

  1. Structural Variation within the Amygdala and Ventromedial Prefrontal Cortex Predict Memory for Impressions in Older Adults

    Directory of Open Access Journals (Sweden)

    Brittany Shane Cassidy

    2012-08-01

    Full Text Available Research has shown that lesions to regions involved in social and emotional cognition disrupt socioemotional processing and memory. We investigated how structural variation of regions involved in socioemotional memory (ventromedial prefrontal cortex [vmPFC], amygdala, as opposed to a region implicated in explicit memory (hippocampus, affected memory for impressions in young and older adults. Anatomical MRI scans for fifteen young and fifteen older adults were obtained and reconstructed to gather information about cortical thickness and subcortical volume. Young adults had greater amygdala and hippocampus volumes than old, and thicker left vmPFC than old, although right vmPFC thickness did not differ across the age groups. Participants formed behavior-based impressions and responded to interpersonally meaningful, social but interpersonally irrelevant, or non-social prompts, and completed a memory test. Results showed that greater left amygdala volume predicted enhanced overall memory for impressions in older but not younger adults. Increased right vmPFC thickness in older, but not younger, adults correlated with enhanced memory for impressions formed in the interpersonally meaningful context. Hippocampal volume was not predictive of social memory in young or older adults. These findings demonstrate the importance of structural variation in regions linked to socioemotional processing in the retention of impressions with age, and suggest that the amygdala and vmPFC play an integral role when encoding and retrieving social information.

  2. α/β-Hydrolase Domain 6 in the Ventromedial Hypothalamus Controls Energy Metabolism Flexibility

    Directory of Open Access Journals (Sweden)

    Alexandre Fisette

    2016-10-01

    Full Text Available α/β-Hydrolase domain 6 (ABHD6 is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG. Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMHKO have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges. VMHKO mice exhibited blunted fasting-induced feeding and reduced food intake, energy expenditure, and adaptive thermogenesis in response to cold exposure, high-fat feeding, and dieting (transition to a low-fat diet. Our findings identify ABHD6 as a regulator of the counter-regulatory responses to major metabolic shifts, including fasting, nutrient excess, cold, and dieting, thereby highlighting the importance of ABHD6 in the VMH in mediating energy metabolism flexibility.

  3. Economic decision-making in psychopathy: a comparison with ventromedial prefrontal lesion patients.

    Science.gov (United States)

    Koenigs, Michael; Kruepke, Michael; Newman, Joseph P

    2010-06-01

    Psychopathy, which is characterized by a constellation of antisocial behavioral traits, may be subdivided on the basis of etiology: "primary" (low-anxious) psychopathy is viewed as a direct consequence of some core intrinsic deficit, whereas "secondary" (high-anxious) psychopathy is viewed as an indirect consequence of environmental factors or other psychopathology. Theories on the neurobiology of psychopathy have targeted dysfunction within ventromedial prefrontal cortex (vmPFC) as a putative mechanism, yet the relationship between vmPFC function and psychopathy subtype has not been fully explored. In this study, we administered two laboratory decision-making tasks (the Ultimatum Game and the Dictator Game) to a group of prisoners (n=47) to determine whether the different subtypes of psychopathy (primary vs. secondary) are associated with characteristic patterns of economic decision-making, and furthermore, whether either subtype exhibits similar performance to patients with vmPFC lesions. Comparing primary psychopaths (n=6) to secondary psychopaths (n=6) and non-psychopaths (n=22), we found that primary psychopathy was associated with significantly lower acceptance rates of unfair Ultimatum offers and lower offer amounts in the Dictator Game. Moreover, primary psychopaths were quantitatively similar to vmPFC lesion patients in their response patterns. These results support the purported connection between psychopathy and vmPFC dysfunction, bolster the distinction between primary and secondary psychopathy, and demonstrate the utility of laboratory economic decision-making tests in differentiating clinical subgroups.

  4. The Role of the Ventromedial Prefrontal Cortex in Purchase Intent Among Older Adults

    Science.gov (United States)

    Koestner, Bryan P.; Hedgcock, William; Halfmann, Kameko; Denburg, Natalie L.

    2016-01-01

    Older adults are frequently the targets of scams and deception, with millions of individuals being affected each year in the United States alone. Previous research has shown that the ventromedial prefrontal cortex (vmPFC) may play a role in vulnerability to fraud. The current study examined brain activation patterns in relation to susceptibility to scams and fraud using functional magnetic resonance imaging (fMRI). Twenty-eight healthy, community-dwelling older adults were subdivided into groups of impaired and unimpaired decision makers as determined by their performance on the Iowa Gambling Task (IGT). While in the scanner, the participants viewed advertisements that were created directly from cases deemed deceptive by the Federal Trade Commission (FTC). We then obtained behavioral measures involving comprehension of claims and purchase intention of the product in each advertisement. Contrasts show brain activity in the vmPFC was less correlated with purchase intention in impaired vs. unimpaired older adult decision makers. Our results have important implications for both future research and recognizing the possible causes of fraud susceptibility among older adults. PMID:27536238

  5. Nutrition labels influence value computation of food products in the ventromedial prefrontal cortex.

    Science.gov (United States)

    Enax, Laura; Hu, Yang; Trautner, Peter; Weber, Bernd

    2015-04-01

    Prevalence of obesity is high in most industrialized nations, and therefore, it is crucial to understand contextual factors underlying food choice. Nutrition labels are public policy interventions designed to adequately inform consumers about nutritional value and overall healthiness of food products. The present study examines how different nutrition labels, namely a purely information-based label (guideline daily amount, GDA) and a more explicit traffic light (TL) label, influence product valuation and choice in a functional MRI setting. Thirty-five healthy participants across different BMIs were instructed to valuate healthy and unhealthy food products in combination with one of the two labels and to state their willingness to pay (WTP) for the product. The labeling methods significantly influenced participants' WTP. Red TL signaling activated parts of the left inferior frontal gyrus/dorsolateral prefrontal cortex, a region implicated in self-control in food choice. This region, in the case of red signaling, and the posterior cingulate cortex, in the case of green signaling, showed increased coupling to the valuation system in the ventromedial prefrontal cortex. Our results suggest that explicitly directing attention toward nutritional values using salient nutrition labels triggers neurobiological processes that resemble those utilized by successful dieters choosing healthier products. © 2015 The Obesity Society.

  6. Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity

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    Kinyua, Ann W.; Yang, Dong Joo; Chang, Inik; Kim, Ki Woo

    2016-01-01

    The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet. PMID:27598259

  7. Ventromedial prefrontal damage reduces mind-wandering and biases its temporal focus.

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    Bertossi, Elena; Ciaramelli, Elisa

    2016-11-01

    Mind-wandering, an ubiquitous expression of humans' mental life, reflects a drift of attention away from the current task towards self-generated thoughts, and has been associated with activity in the brain default network. To date, however, little is understood about the contribution of individual nodes of this network to mind-wandering. Here, we investigated whether the ventromedial prefrontal cortex (vmPFC) is critically involved in mind-wandering, by studying the propensity to mind-wander in patients with lesion to the vmPFC (vmPFC patients), control patients with lesions not involving the vmPFC, and healthy individuals. Participants performed three tasks varying in cognitive demands while their thoughts were periodically sampled, and a self-report scale of daydreaming in daily life. vmPFC patients exhibited reduced mind-wandering rates across tasks, and claimed less frequent daydreaming, than both healthy and brain-damaged controls. vmPFC damage reduced off-task thoughts related to the future, while it promoted those about the present. These results indicate that vmPFC critically supports mind-wandering, possibly by helping to construct future-related scenarios and thoughts that have the potential to draw attention inward, away from the ongoing tasks.

  8. Coordinated activation of premotor and ventromedial prefrontal cortices during vicarious reward.

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    Shimada, Sotaro; Matsumoto, Madoka; Takahashi, Hidefumi; Yomogida, Yukihito; Matsumoto, Kenji

    2016-03-01

    The vicarious reward we receive from watching likable others obtaining a positive outcome is a pervasive phenomenon, yet its neural correlates are poorly understood. Here, we conducted a series of functional magnetic resonance imaging experiments to test the hypothesis that the brain areas responsible for action observation and reward processing work in a coordinated fashion during vicarious reward. In the first experiment (manipulation phase), the participant was instructed to cheer for a particular player in a two-player competitive game (Rock-Paper-Scissors). This manipulation made participants feel more unity with that player and resulted in unity-related activation in the premotor area during action observation. In the following main experiment, the participant witnessed the previously cheered-for or non-cheered-for player succeed in a new solitary game (a stopwatch game). The ventromedial prefrontal cortex (vmPFC) was activated when the cheered-for player succeeded in the game but not when the other player did. Interestingly, this vmPFC activation was functionally connected with premotor activation only during the cheered-for player's success. These results suggest that vicarious reward is processed in the vmPFC-premotor network, which is activated specifically by the success of the other person with whom the individual feels unity and closeness.

  9. Investigating the role of the ventromedial prefrontal cortex (vmPFC in the assessment of brands

    Directory of Open Access Journals (Sweden)

    Jose Paulo eSantos

    2011-06-01

    Full Text Available The ventromedial prefrontal cortex (vmPFC is believed to be important in everyday preference judgments, processing emotions during decision-making. However, there is still controversy in the literature regarding the participation of the vmPFC. To further elucidate the contribution of the vmPFC in brand preference, we designed a functional magnetic resonance imaging (fMRI study where 18 subjects assessed positive, indifferent and fictitious brands. Also, both the period during and after the decision process were analyzed, hoping to unravel temporally the role of the vmPFC, using modeled and model-free fMRI analysis. Considering together the period before and after decision-making, there was activation of the vmPFC when comparing positive with indifferent or fictitious brands. However, when the decision-making period was separated from the moment after the response, and especially for positive brands, the vmPFC was more active after the choice than during the decision process itself, challenging some of the existing literature. The results of the present study support the notion that the vmPFC may be unimportant in the decision stage of brand preference, questioning theories that postulate that the vmPFC is in the origin of such a choice. Further studies are needed to investigate in detail why the vmPFC seems to be involved in brand preference only after the decision process.

  10. Investigating the role of the ventromedial prefrontal cortex in the assessment of brands.

    Science.gov (United States)

    Santos, José Paulo; Seixas, Daniela; Brandão, Sofia; Moutinho, Luiz

    2011-01-01

    The ventromedial prefrontal cortex (vmPFC) is believed to be important in everyday preference judgments, processing emotions during decision-making. However, there is still controversy in the literature regarding the participation of the vmPFC. To further elucidate the contribution of the vmPFC in brand preference, we designed a functional magnetic resonance imaging (fMRI) study where 18 subjects assessed positive, indifferent, and fictitious brands. Also, both the period during and after the decision process were analyzed, hoping to unravel temporally the role of the vmPFC, using modeled and model-free fMRI analysis. Considering together the period before and after decision-making, there was activation of the vmPFC when comparing positive with indifferent or fictitious brands. However, when the decision-making period was separated from the moment after the response, and especially for positive brands, the vmPFC was more active after the choice than during the decision process itself, challenging some of the existing literature. The results of the present study support the notion that the vmPFC may be unimportant in the decision stage of brand preference, questioning theories that postulate that the vmPFC is in the origin of such a choice. Further studies are needed to investigate in detail why the vmPFC seems to be involved in brand preference only after the decision process.

  11. The Role of the Ventromedial Prefrontal Cortex in Purchase Intent Among Older Adults.

    Science.gov (United States)

    Koestner, Bryan P; Hedgcock, William; Halfmann, Kameko; Denburg, Natalie L

    2016-01-01

    Older adults are frequently the targets of scams and deception, with millions of individuals being affected each year in the United States alone. Previous research has shown that the ventromedial prefrontal cortex (vmPFC) may play a role in vulnerability to fraud. The current study examined brain activation patterns in relation to susceptibility to scams and fraud using functional magnetic resonance imaging (fMRI). Twenty-eight healthy, community-dwelling older adults were subdivided into groups of impaired and unimpaired decision makers as determined by their performance on the Iowa Gambling Task (IGT). While in the scanner, the participants viewed advertisements that were created directly from cases deemed deceptive by the Federal Trade Commission (FTC). We then obtained behavioral measures involving comprehension of claims and purchase intention of the product in each advertisement. Contrasts show brain activity in the vmPFC was less correlated with purchase intention in impaired vs. unimpaired older adult decision makers. Our results have important implications for both future research and recognizing the possible causes of fraud susceptibility among older adults.

  12. The blockage of ventromedial hypothalamus CRF type 2 receptors impairs escape responses in the elevated T-maze.

    Science.gov (United States)

    Silva, Mariana S C F; Souza, Thaissa M O; Pereira, Bruno A; Ribeiro, Daniel A; Céspedes, Isabel C; Bittencourt, Jackson C; Viana, Milena B

    2017-06-30

    In a previous study, the administration of corticotrophin-releasing factor (CRF) into the dorsomedial hypothalamus (DMH), a region that modulates defensive reactions, was shown to facilitate elevated T-maze (ETM) avoidance responses, an anxiogenic-like effect. Intra-DMH administration of the CRF type 1 receptor (CRFR1) antagonist antalarmin induced anxiolytic-like effects and counteracted the anxiogenic effects of CRF. The present study further investigates the role played by CRF receptors of the medial hypothalamus in anxiety. For that, male wistar rats were treated with CRFR1 and CRFR2-modulating drugs in the DMH or VMH, another hypothalamic nucleus implicated with defensive and emotional behavior, and tested in the ETM for inhibitory avoidance and escape measurements. In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. The results showed that intra-VMH CRF or antalarmin did not alter ETM avoidance or escape performance. Intra-VMH injection of the CRFR2 preferential antagonist antisauvagine-30 or of the selective CRFR2 antagonist astressin 2-B inhibited escape performance, a panicolytic-like effect, without altering avoidance reactions. The CRFR2 agonist urocortin-2 intra-VMH was by itself without effect but blocked the effects of astressin 2-B. None of the drugs administered into the DMH altered ETM measurements. Additionally, none of the compounds altered locomotor activity measurements. These results suggest that VMH CRFR2 modulate a defensive response associated with panic disorder and are of relevance to the better understanding of the neural mechanisms underlying this pathological condition. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Alterations in hypothalamic gene expression following Roux-en-Y gastric bypass

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    Barkholt, Pernille; Pedersen, Philip J.; Hay-Schmidt, Anders; Jelsing, Jacob; Hansen, Henrik H.; Vrang, Niels

    2016-01-01

    Objective The role of the central nervous system in mediating metabolic effects of Roux-en-Y gastric bypass (RYGB) surgery is poorly understood. Using a rat model of RYGB, we aimed to identify changes in gene expression of key hypothalamic neuropeptides known to be involved in the regulation of energy balance. Methods Lean male Sprague-Dawley rats underwent either RYGB or sham surgery. Body weight and food intake were monitored bi-weekly for 60 days post-surgery. In situ hybridization mRNA analysis of hypothalamic AgRP, NPY, CART, POMC and MCH was applied to RYGB and sham animals and compared with ad libitum fed and food-restricted rats. Furthermore, in situ hybridization mRNA analysis of dopaminergic transmission markers (TH and DAT) was applied in the midbrain. Results RYGB surgery significantly reduced body weight and intake of a highly palatable diet but increased chow consumption compared with sham operated controls. In the arcuate nucleus, RYGB surgery increased mRNA levels of orexigenic AgRP and NPY, whereas no change was observed in anorexigenic CART and POMC mRNA levels. A similar pattern was seen in food-restricted versus ad libitum fed rats. In contrast to a significant increase of orexigenic MCH mRNA levels in food-restricted animals, RYGB did not change MCH expression in the lateral hypothalamus. In the VTA, RYGB surgery induced a reduction in mRNA levels of TH and DAT, whereas no changes were observed in the substantia nigra relative to sham surgery. Conclusion RYGB surgery increases the mRNA levels of hunger-associated signaling markers in the rat arcuate nucleus without concomitantly increasing downstream MCH expression in the lateral hypothalamus, suggesting that RYGB surgery puts a brake on orexigenic hypothalamic output signals. In addition, down-regulation of midbrain TH and DAT expression suggests that altered dopaminergic activity also contributes to the reduced intake of palatable food in RYGB rats. PMID:27069869

  14. Obesity-inducing hypothalamic knife cuts: effects on lipolysis and blood insulin levels.

    Science.gov (United States)

    Bray, G A; Sclafani, A; Novin, D

    1982-09-01

    The effect of two experimental manipulations designed to mobilize lipids from adipose tissue have been investigated in rats with parasagittal knife cuts in the ventromedial hypothalamus (VMH). Those animals which displayed hyperphagia during the initial 5 days VMH knife cuts were then restricted in food intake to reduce body weights to levels comparable to that of the sham-operated controls. Two weeks following the knife-cut lesions, or sham operations, animals in the first experiment were exposed to the cold for 60 min, and those in the second experiment were injected with 2-deoxy-D-glucose (2-DG). The injections of 2-DG increased the level of glycerol in the control animals but not in the animals with VMH knife cuts. Both groups showed a rise in glucose. Plasma insulin and triglycerides were the same in both groups. Exposure to the cold increased the level of glycerol in both groups. The insulin levels were lower in the corresponding groups with knife cuts. These studies show that VMH knife cuts do not produce hyperinsulinemia in pair-gained rats.

  15. Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss.

    Science.gov (United States)

    Turner, Russell T; Dube, Michael; Branscum, Adam J; Wong, Carmen P; Olson, Dawn A; Zhong, Xiaoying; Kweh, Mercedes F; Larkin, Iske V; Wronski, Thomas J; Rosen, Clifford J; Kalra, Satya P; Iwaniec, Urszula T

    2015-12-01

    Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (-4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (-80%), serum leptin (-77%), and serum IGF1 (-34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (PLeptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

  16. Translational relevance of rodent models of hypothalamic-pituitary-adrenal function and stressors in adolescence

    Directory of Open Access Journals (Sweden)

    Cheryl M. McCormick

    2017-02-01

    Full Text Available Elevations in glucocorticoids that result from environmental stressors can have programming effects on brain structure and function when the exposure occurs during sensitive periods that involve heightened neural development. In recent years, adolescence has gained increasing attention as another sensitive period of development, a period in which pubertal transitions may increase the vulnerability to stressors. There are similarities in physical and behavioural development between humans and rats, and rats have been used effectively as an animal model of adolescence and the unique plasticity of this period of ontogeny. This review focuses on benefits and challenges of rats as a model for translational research on hypothalamic-pituitary-adrenal (HPA function and stressors in adolescence, highlighting important parallels and contrasts between adolescent rats and humans, and we review the main stress procedures that are used in investigating HPA stress responses and their consequences in adolescence in rats. We conclude that a greater focus on timing of puberty as a factor in research in adolescent rats may increase the translational relevance of the findings.

  17. Hypothalamic inflammation: a double-edged sword to nutritional diseases

    Science.gov (United States)

    Cai, Dongsheng; Liu, Tiewen

    2015-01-01

    The hypothalamus is one of the master regulators of various physiological processes, including energy balance and nutrient metabolism. These regulatory functions are mediated by discrete hypothalamic regions that integrate metabolic sensing with neuroendocrine and neural controls of systemic physiology. Neurons and non-neuronal cells in these hypothalamic regions act supportively to execute metabolic regulations. Under conditions of brain and hypothalamic inflammation, which may result from overnutrition-induced intracellular stresses or disease-associated systemic inflammatory factors, extracellular and intracellular environments of hypothalamic cells are disrupted, leading to central metabolic dysregulations and various diseases. Recent research has begun to elucidate the effects of hypothalamic inflammation in causing diverse components of metabolic syndrome leading to diabetes and cardiovascular disease. These new understandings have provocatively expanded previous knowledge on the cachectic roles of brain inflammatory response in diseases, such as infections and cancers. This review describes the molecular and cellular characteristics of hypothalamic inflammation in metabolic syndrome and related diseases as opposed to cachectic diseases, and also discusses concepts and potential applications of inhibiting central/hypothalamic inflammation to treat nutritional diseases. PMID:22417140

  18. Risk factors for mortality caused by hypothalamic obesity in children with hypothalamic tumours.

    Science.gov (United States)

    Haliloglu, B; Atay, Z; Guran, T; Abalı, S; Bas, S; Turan, S; Bereket, A

    2016-10-01

    Hypothalamic obesity (HyOb) is a common complication of childhood hypothalamic tumours. Patients with HyOb probably have a higher mortality rate than those with other types of obesity due in many cases to obstructive sleep apnoea/hypoventilation. To identify predictive factors for mortality caused by HyOb in children. Twenty children with HyOb secondary to hypothalamic tumours that were followed-up for ≥3 years and aged 6 years at diagnosis (3.71 ± 1.96 vs. 0.83 ± 0.73, P  1 SDS after 6 months of therapy (RR: 8.4, P obesity-related mortality rates were higher in the patients aged  0.05). The mortality rate was also 3.7-fold higher in the patients with a maximum BMI SDS ≥ 3 at any time during the first 3 years after therapy(P > 0.05). An increase in BMI SDS after 6 months of therapy was observed to be a risk factor for mortality caused by HyOb. In addition, age obesity is required. © 2015 World Obesity.

  19. Lateral hypothalamic circuits for feeding and reward.

    Science.gov (United States)

    Stuber, Garret D; Wise, Roy A

    2016-02-01

    In experiments conducted over 60 years ago, the lateral hypothalamic area (LHA) was identified as a critical neuroanatomical substrate for motivated behavior. Electrical stimulation of the LHA induces voracious feeding even in well-fed animals. In the absence of food, animals will work tirelessly, often lever-pressing thousands of times per hour, for electrical stimulation at the same site that provokes feeding, drinking and other species-typical motivated behaviors. Here we review the classic findings from electrical stimulation studies and integrate them with more recent work that has used contemporary circuit-based approaches to study the LHA. We identify specific anatomically and molecularly defined LHA elements that integrate diverse information arising from cortical, extended amygdala and basal forebrain networks to ultimately generate a highly specified and invigorated behavioral state conveyed via LHA projections to downstream reward and feeding-specific circuits.

  20. Management of optic chiasmatic/hypothalamic astrocytomas in children

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    Steinbok, P.; Hentschel, S.; Almqvist, P.; Cochrane, D.D. [Univ. of British Columbia, British Columbia' s Children' s Hospital, Div. of Pediatric Neurosurgery, Dept. of Surgery, Vancouver, British Columbia (Canada); Poskitt, K. [Univ. of British Columbia, British Columbia' s Children' s Hospital, Dept. of Radiology, Vancouver, British Columbia (Canada)

    2002-05-01

    The management of optic chiasmatic gliomas is controversial, partly related to failure to separate out those tumors involving the optic chiasm only (chiasmatic tumors) from those also involving the hypothalamus (chiasmatic/hypothalamic tumors). The purpose of this study was: (i) to analyze the outcomes of chiasmatic and chiasmatic/hypothalamic tumors separately; and (ii) to determine the appropriateness of recommending radical surgical resection for the chiasmatic/hypothalamic tumors. A retrospective chart review of all newly diagnosed tumors involving the optic chiasm from 1982-1996 at British Columbia's Children's Hospital was performed. There were 32 patients less than 16 years of age, 14 with chiasmatic and 18 with chiasmatic/hypothalamic astrocytomas, with an average duration of follow-up of 5.8 years and 6.3 years, respectively. Ten of the patients with chiasmatic tumors and none with chiasmatic/hypothalamic tumors had neurofibromatosis I. Thirteen of the 14 chiasmatic tumors were managed with observation only, and none had progression requiring active intervention. For the chiasmatic/hypothalamic tumors. eight patients had subtotal resections (>95% resection), six had partial resections (50-95%), three had limited resections (<50%), and one had no surgery. There were fewer complications associated with the limited resections, especially with respect to hypothalamic dysfunction. There was no correlation between the extent of resection (subtotal, partial, or limited) and the time to tumor progression (average 18 months). In conclusion, chiasmatic and chiasmatic/hypothalamic tumors are different entities, which should be separated out for the Purposes of any study. For the chiasmatic/hypothalamic tumors, there was more morbidity and no prolongation of time to progression when radical resections were compared to more limited resections. Therefore, if surgery is performed, it may be appropriate to do a surgical procedure that strives only to provide a

  1. Dynamic localization of glucokinase and its regulatory protein in hypothalamic tanycytes.

    Directory of Open Access Journals (Sweden)

    Magdiel Salgado

    Full Text Available Glucokinase (GK, the hexokinase involved in glucose sensing in pancreatic β cells, is also expressed in hypothalamic tanycytes, which cover the ventricular walls of the basal hypothalamus and are implicated in an indirect control of neuronal activity by glucose. Previously, we demonstrated that GK was preferentially localized in tanycyte nuclei in euglycemic rats, which has been reported in hepatocytes and is suggestive of the presence of the GK regulatory protein, GKRP. In the present study, GK intracellular localization in hypothalamic and hepatic tissues of the same rats under several glycemic conditions was compared using confocal microscopy and Western blot analysis. In the hypothalamus, increased GK nuclear localization was observed in hyperglycemic conditions; however, it was primarily localized in the cytoplasm in hepatic tissue under the same conditions. Both GK and GKRP were next cloned from primary cultures of tanycytes. Expression of GK by Escherichia coli revealed a functional cooperative protein with a S0.5 of 10 mM. GKRP, expressed in Saccharomyces cerevisiae, inhibited GK activity in vitro with a Ki 0.2 µM. We also demonstrated increased nuclear reactivity of both GK and GKRP in response to high glucose concentrations in tanycyte cultures. These data were confirmed using Western blot analysis of nuclear extracts. Results indicate that GK undergoes short-term regulation by nuclear compartmentalization. Thus, in tanycytes, GK can act as a molecular switch to arrest cellular responses to increased glucose.

  2. 新生期使用不同剂量双酚A对雄性大鼠下丘脑-垂体-睾丸轴的影响%Effect of exposure to different doses of Bisphenol A during neonate on hypothalamic -pituitary -testis axis in male rats

    Institute of Scientific and Technical Information of China (English)

    周文文; 孙辉; 陈临琪; 金美芳; 杨帆; 吴海瑛; 谢蓉蓉; 王凤云; 陈秀丽; 陈婷

    2016-01-01

    Objective To explore the effect of neonatal exposure to different doses of Bisphenol A (BPA)on the hypothalamic -pituitary -testis axis in toddler and adolescent male rats.Methods Neonatal male Sprague -Daw-ley rats were randomly divided into 5 groups through random digital table method:control group,vehicle group,low -dose BPA [25 μg/(kg · d)]group,medium -dose BPA [50 μg/(kg · d)]group and high -dose BPA [250μg/(kg·d)]group.The rats were subcutaneously injected with respective agents on postnatal days 1 -7 (PND 1 -7).Pups were sacrificed on PND 22 and PND 50.The hypothalamus and testis were taken and weighed.The hypotha-lamic Kiss -1 mRNA and the testis androgen receptor (AR)mRNA were tested by using real -time fluorescence quan-titative and the levels of serum luteinizing hormone (LH),follicle stimulating hormone (FSH),testosterone (T)were tested by using radio immunity method,and inhibin B was measured by using enzyme linked immunosorbent assay. Results Compared with the controls,the level of serum FSH [(1 .610 0 ±0.693 2)IU /L,(1 .574 3 ±0.675 0)IU /L vs (2.362 9 ±0.580 3)IU /L](F =3.314,P =0.026),LH [(3.876 3 ±0.908 0)IU /L,(3.603 8 ±1 .350 2)IU /L vs (5.302 5 ±0.768 4)IU /L](F =3.1 39,P =0.027)and T [(0.383 8 ±0.1 77 8)μg/L,(0.442 5 ±0.21 4 1 )μg/L vs (0.782 5 ±0.282 1 )μg/L](F =5.1 06,P <0.01 )of medium and high -dose BPA groups,were decreased in PND 22,and the organ coefficient of testis [(0.952 90 ±0.049 1 5)%,(0.969 20 ±0.045 82)% vs (1 .022 80 ± 0.01 1 08)%](F =1 0.326,P <0.01 )and serum T [(1 .758 6 ±0.369 6)μg/L,(1 .71 8 8 ±0.395 7)μg/L vs (3.357 5 ±0.749 8)μg/L](F =1 3.799,P =0.01 2)were significantly decreased in PND 50.In high -dose BPA group of PND 22,the expression of hypothalamic Kiss -1 mRNA (0.068 80 ±0.01 1 79)was increased compared with the other groups (F =272.1 25,P <0.01 ),while in PND 50,compared with control group,the Kiss -1 mRNA (0.002 00 ±0.000 25,0.001 90 ±0.000 48 vs 0.001 40 ±0.000 1 7)of medium -and

  3. Amygdala perfusion is predicted by its functional connectivity with the ventromedial prefrontal cortex and negative affect.

    Directory of Open Access Journals (Sweden)

    Garth Coombs

    Full Text Available BACKGROUND: Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect. It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1 amygdala over-activity and 2 reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states. METHODS: Here we used resting-state arterial spin labeling (ASL and blood oxygenation level dependent (BOLD functional magnetic resonance imaging (fMRI in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF and functional connectivity (correlated fluctuations in the BOLD signal of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA, and subsyndromal anxiety levels in 38 healthy subjects. RESULTS: BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety. CONCLUSIONS: These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.

  4. Activity in ventromedial prefrontal cortex during self-related processing: positive subjective value or personal significance?

    Science.gov (United States)

    Kim, Kyungmi; Johnson, Marcia K

    2015-04-01

    Well-being and subjective experience of a coherent world depend on our sense of 'self' and relations between the self and the environment (e.g. people, objects and ideas). The ventromedial prefrontal cortex (vMPFC) is involved in self-related processing, and disrupted vMPFC activity is associated with disruptions of emotional/social functioning (e.g. depression and autism). Clarifying precise function(s) of vMPFC in self-related processing is an area of active investigation. In this study, we sought to more specifically characterize the function of vMPFC in self-related processing, focusing on two alternative accounts: (i) assignment of positive subjective value to self-related information and (ii) assignment of personal significance to self-related information. During functional magnetic resonance imaging (fMRI), participants imagined owning objects associated with either their perceived ingroup or outgroup. We found that for ingroup-associated objects, vMPFC showed greater activity for objects with increased than decreased post-ownership preference. In contrast, for outgroup-associated objects, vMPFC showed greater activity for objects with decreased than increased post-ownership preference. Our findings support the idea that the function of vMPFC in self-related processing may not be to represent/evaluate the 'positivity' or absolute preference of self-related information but to assign personal significance to it based on its meaning/function for the self. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  5. Mindfulness training modulates value signals in ventromedial prefrontal cortex through input from insular cortex.

    Science.gov (United States)

    Kirk, Ulrich; Gu, Xiaosi; Harvey, Ann H; Fonagy, Peter; Montague, P Read

    2014-10-15

    Neuroimaging research has demonstrated that ventromedial prefrontal cortex (vmPFC) encodes value signals that can be modulated by top-down cognitive input such as semantic knowledge, price incentives, and monetary favors suggesting that such biases may have an identified biological basis. It has been hypothesized that mindfulness training (MT) provides one path for gaining control over such top-down influences; yet, there have been no direct tests of this hypothesis. Here, we probe the behavioral and neural effects of MT on value signals in vmPFC in a randomized longitudinal design of 8 weeks of MT on an initially naïve subject cohort. The impact of this within-subject training was assessed using two paradigms: one that employed primary rewards (fruit juice) in a simple conditioning task and another that used a well-validated art-viewing paradigm to test bias of monetary favors on preference. We show that MT behaviorally censors the top-down bias of monetary favors through a measurable influence on value signals in vmPFC. MT also modulates value signals in vmPFC to primary reward delivery. Using a separate cohort of subjects we show that 8 weeks of active control training (ACT) generates the same behavioral impact also through an effect on signals in the vmPFC. Importantly, functional connectivity analyses show that value signals in vmPFC are coupled with bilateral posterior insula in the MT groups in both paradigms, but not in the ACT groups. These results suggest that MT integrates interoceptive input from insular cortex in the context of value computations of both primary and secondary rewards.

  6. Investment and repayment in a trust game after ventromedial prefrontal damage.

    Science.gov (United States)

    Moretto, Giovanna; Sellitto, Manuela; di Pellegrino, Giuseppe

    2013-01-01

    Although trust and reciprocity are ubiquitous in social exchange, their neurobiological substrate remains largely unknown. Here, we investigated the effect of damage to the ventromedial prefrontal cortex (vmPFC)-a brain region critical for valuing social information-on individuals' decisions in a trust game and in a risk game. In the trust game, one player, the investor, is endowed with a sum of money, which she can keep or invest. The amount she decides to invest is tripled and sent to the other player, the trustee, who then decides what fraction to return to the investor. In separate runs, ten patients with focal bilateral damage to the vmPFC and control participants made decision while playing in the role of either investor or trustee with different anonymous counterparts in each run. A risk game was also included in which the investor faced exactly the same decisions as in the trust game, but a random device (i.e., a computer), not another player, determined the final payoffs. Results showed that vmPFC patients' investments were not modulated by the type of opponent player (e.g., human vs. computer) present in the environment. Thus, vmPFC patients showed comparable risk-taking preferences both in social (trust game) and nonsocial (risk game) contexts. In stark contrast, control participants were less willing to take risk and invest when they believed that they were interacting with people than a computer. Furthermore, when acted as trustee, vmPFC patients made lower back transfers toward investors, thereby showing less reciprocity behavior. Taken together, these results indicate that social valuation and emotion subserved by vmPFC have a critical role in trusting and reciprocity decisions. The present findings support the hypothesis that vmPFC damage may impair affective systems specifically designed for mediating social transaction with other individuals.

  7. Functional compensation in the ventromedial prefrontal cortex improves memory-dependent decisions in older adults.

    Science.gov (United States)

    Lighthall, Nichole R; Huettel, Scott A; Cabeza, Roberto

    2014-11-19

    Everyday consumer choices frequently involve memory, as when we retrieve information about consumer products when making purchasing decisions. In this context, poor memory may affect decision quality, particularly in individuals with memory decline, such as older adults. However, age differences in choice behavior may be reduced if older adults can recruit additional neural resources that support task performance. Although such functional compensation is well documented in other cognitive domains, it is presently unclear whether it can support memory-guided decision making and, if so, which brain regions play a role in compensation. The current study engaged younger and older humans in a memory-dependent choice task in which pairs of consumer products from a popular online-shopping site were evaluated with different delays between the first and second product. Using functional imaging (fMRI), we found that the ventromedial prefrontal cortex (vmPFC) supports compensation as defined by three a priori criteria: (1) increased vmPFC activation was observed in older versus younger adults; (2) age-related increases in vmPFC activity were associated with increased retrieval demands; and (3) increased vmPFC activity was positively associated with performance in older adults-evidence of successful compensation. Extending these results, we observed evidence for compensation in connectivity between vmPFC and the dorsolateral PFC during memory-dependent choice. In contrast, we found no evidence for age differences in value-related processing or age-related compensation for choices without delayed retrieval. Together, these results converge on the conclusion that age-related decline in memory-dependent choice performance can be minimized via functional compensation in vmPFC.

  8. Anhedonia and general distress show dissociable ventromedial prefrontal cortex connectivity in major depressive disorder.

    Science.gov (United States)

    Young, C B; Chen, T; Nusslock, R; Keller, J; Schatzberg, A F; Menon, V

    2016-05-17

    Anhedonia, the reduced ability to experience pleasure in response to otherwise rewarding stimuli, is a core symptom of major depressive disorder (MDD). Although the posterior ventromedial prefrontal cortex (pVMPFC) and its functional connections have been consistently implicated in MDD, their roles in anhedonia remain poorly understood. Furthermore, it is unknown whether anhedonia is primarily associated with intrinsic 'resting-state' pVMPFC functional connectivity or an inability to modulate connectivity in a context-specific manner. To address these gaps, a pVMPFC region of interest was first identified using activation likelihood estimation meta-analysis. pVMPFC connectivity was then examined in relation to anhedonia and general distress symptoms of depression, using both resting-state and task-based functional magnetic resonance imaging involving pleasant music, in current MDD and healthy control groups. In MDD, pVMPFC connectivity was negatively correlated with anhedonia but not general distress during music listening in key reward- and emotion-processing regions, including nucleus accumbens, ventral tegmental area/substantia nigra, orbitofrontal cortex and insula, as well as fronto-temporal regions involved in tracking complex sound sequences, including middle temporal gyrus and inferior frontal gyrus. No such dissociations were observed in the healthy controls, and resting-state pVMPFC connectivity did not dissociate anhedonia from general distress in either group. Our findings demonstrate that anhedonia in MDD is associated with context-specific deficits in pVMPFC connectivity with the mesolimbic reward system when encountering pleasurable stimuli, rather than a static deficit in intrinsic resting-state connectivity. Critically, identification of functional circuits associated with anhedonia better characterizes MDD heterogeneity and may help track of one of its core symptoms.

  9. Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?

    Science.gov (United States)

    Tranel, Daniel; Damasio, Hanna; Denburg, Natalie L; Bechara, Antoine

    2005-12-01

    We found previously in a lesion study that the right-sided sector of the ventromedial prefrontal cortices (VMPCs) was critical for social/emotional functioning and decision-making, whereas the left side appeared to be less important. It so happened that all but one of the subjects in that study were men, and the one woman did not fit the pattern very well. This prompted a follow-up investigation, in which we explored the following question: Does gender play a role in the development of defects in social conduct, emotional functioning and decision-making, following unilateral VMPC damage? We culled from our Patient Registry same-sex pairs of men or women patients who had comparable unilateral VMPC damage in either the left or right hemisphere. Two male pairs and one female pair were formed, and we included two additional women with unilateral right VMPC damage (8 patients in all). The domains of measurement covered social conduct, emotional processing and personality, and decision-making. We found a systematic effect of gender on the pattern of left-right asymmetry in VMPC. In men, there were severe defects following unilateral right VMPC damage, but not following left-sided damage. In women, there were defects following unilateral left VMPC damage; following right-sided damage, however, defects were mild or absent. The findings suggest that men and women may use different strategies to solve similar problems--e.g. men may use a more holistic, gestalt-type strategy, and women may use a more analytic, verbally-mediated strategy. Such differences could reflect asymmetric, gender-related differences in the neurobiology of left and right VMPC sectors.

  10. Integrative moral judgment: dissociating the roles of the amygdala and ventromedial prefrontal cortex.

    Science.gov (United States)

    Shenhav, Amitai; Greene, Joshua D

    2014-03-26

    A decade's research highlights a critical dissociation between automatic and controlled influences on moral judgment, which is subserved by distinct neural structures. Specifically, negative automatic emotional responses to prototypically harmful actions (e.g., pushing someone off of a footbridge) compete with controlled responses favoring the best consequences (e.g., saving five lives instead of one). It is unknown how such competitions are resolved to yield "all things considered" judgments. Here, we examine such integrative moral judgments. Drawing on insights from research on self-interested, value-based decision-making in humans and animals, we test a theory concerning the respective contributions of the amygdala and ventromedial prefrontal cortex (vmPFC) to moral judgment. Participants undergoing fMRI responded to moral dilemmas, separately evaluating options for their utility (Which does the most good?), emotional aversiveness (Which feels worse?), and overall moral acceptability. Behavioral data indicate that emotional aversiveness and utility jointly predict "all things considered" integrative judgments. Amygdala response tracks the emotional aversiveness of harmful utilitarian actions and overall disapproval of such actions. During such integrative moral judgments, the vmPFC is preferentially engaged relative to utilitarian and emotional assessments. Amygdala-vmPFC connectivity varies with the role played by emotional input in the task, being the lowest for pure utilitarian assessments and the highest for pure emotional assessments. These findings, which parallel those of research on self-interested economic decision-making, support the hypothesis that the amygdala provides an affective assessment of the action in question, whereas the vmPFC integrates that signal with a utilitarian assessment of expected outcomes to yield "all things considered" moral judgments.

  11. Functional Compensation in the Ventromedial Prefrontal Cortex Improves Memory-Dependent Decisions in Older Adults

    Science.gov (United States)

    Huettel, Scott A.; Cabeza, Roberto

    2014-01-01

    Everyday consumer choices frequently involve memory, as when we retrieve information about consumer products when making purchasing decisions. In this context, poor memory may affect decision quality, particularly in individuals with memory decline, such as older adults. However, age differences in choice behavior may be reduced if older adults can recruit additional neural resources that support task performance. Although such functional compensation is well documented in other cognitive domains, it is presently unclear whether it can support memory-guided decision making and, if so, which brain regions play a role in compensation. The current study engaged younger and older humans in a memory-dependent choice task in which pairs of consumer products from a popular online-shopping site were evaluated with different delays between the first and second product. Using functional imaging (fMRI), we found that the ventromedial prefrontal cortex (vmPFC) supports compensation as defined by three a priori criteria: (1) increased vmPFC activation was observed in older versus younger adults; (2) age-related increases in vmPFC activity were associated with increased retrieval demands; and (3) increased vmPFC activity was positively associated with performance in older adults—evidence of successful compensation. Extending these results, we observed evidence for compensation in connectivity between vmPFC and the dorsolateral PFC during memory-dependent choice. In contrast, we found no evidence for age differences in value-related processing or age-related compensation for choices without delayed retrieval. Together, these results converge on the conclusion that age-related decline in memory-dependent choice performance can be minimized via functional compensation in vmPFC. PMID:25411493

  12. Harming kin to save strangers: further evidence for abnormally utilitarian moral judgments after ventromedial prefrontal damage.

    Science.gov (United States)

    Thomas, Bradley C; Croft, Katie E; Tranel, Daniel

    2011-09-01

    The ventromedial PFC (vmPFC) has been implicated as a critical neural substrate mediating the influence of emotion on moral reasoning. It has been shown that the vmPFC is especially important for making moral judgments about "high-conflict" moral dilemmas involving direct personal actions, that is, scenarios that pit compelling utilitarian considerations of aggregate welfare against the highly emotionally aversive act of directly causing harm to others [Koenigs, M., Young, L., Adolphs, R., Tranel, D., Cushman, F., Hauser, M., et al. Damage to the prefrontal cortex increases utilitarian moral judgments. Nature, 446, 908-911, 2007]. The current study was designed to elucidate further the role of the vmPFC in high-conflict moral judgments, including those that involve indirect personal actions, such as indirectly causing harm to one's kin to save a group of strangers. We found that patients with vmPFC lesions were more likely than brain-damaged and healthy comparison participants to endorse utilitarian outcomes on high-conflict dilemmas regardless of whether the dilemmas (1) entailed direct versus indirect personal harms and (2) were presented from the Self versus Other perspective. In addition, all groups were more likely to endorse utilitarian outcomes in the Other perspective as compared with the Self perspective. These results provide important extensions of previous work, and the findings align with the proposal that the vmPFC is critical for reasoning about moral dilemmas in which anticipating the social-emotional consequences of an action (e.g., guilt or remorse) is crucial for normal moral judgments [Greene, J. D. Why are VMPFC patients more utilitarian?: A dual-process theory of moral judgment explains. Trends in Cognitive Sciences, 11, 322-323, 2007; Koenigs, M., Young, L., Adolphs, R., Tranel, D., Cushman, F., Hauser, M., et al. Damage to the prefrontal cortex increases utilitarian moral judgments. Nature, 446, 908-911, 2007].

  13. Inhibition of histamine release by local and intracerebroventricular infusion of galanin in hypothalamus, hippocampus and prefrontal cortex of awake rat: A microdialysis study.

    Science.gov (United States)

    Yoshitake, Shimako; Ijiri, Soichiro; Kehr, Jan; Yoshitake, Takashi

    2013-02-08

    The neuropeptide galanin is co-localized with histamine in subpopulations of neurons in the tuberomammillary nucleus suggesting its involvement in modulating histaminergic neurotransmission. The purpose of the present study was to investigate, by use of microdialysis, the effects of local intraparenchymal (combined infusion and microdialysis probe), and intracerebroventricular (i.c.v.) infusions of galanin on extracellular levels of histamine in its major projecting areas, ventromedial hypothalamic nucleus ventrolateral part (VMHVL), CA3 area of ventral hippocampus (vHipp) and medial prefrontal cortex (mPFC) in separate groups (n=5 rats/each) of freely moving rats. Galanin (0.5nmol and 1.5nmol) dose-dependently decreased the basal histamine levels in the VMHVL to 77.1% (i.c.v.) at 40min and to 82.1% (intra-VMHVL infusion) already at 20min, of the control group (32.6±3.5fmol/10μl), whereas only 1.5nmol i.c.v. galanin and not the local infusions deceased the histamine levels in the vHipp (8.4±0.6fmol/10μl) to 82.8% and in mPFC (9.8±0.9fmol/10μl) to 87.5%. It is concluded that central administration of galanin decreased the basal extracellular histamine levels in major histamine projecting areas, however, these effects were less prominent than those observed for 5-HT (Kehr et al., 2002 [12]) and ACh (Yoshitake et al., 2011 [38]) in the ventral hippocampus following i.c.v. and/or local galanin infusions.

  14. Effects of spaceflight on hypothalamic peptide systems controlling pituitary growth hormone dynamics

    Science.gov (United States)

    Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.

    1992-01-01

    Possible effects of reduced gravity on central hypophysiotropic systems controlling growth hormone (GH) secretion were investigated in rats flown on Cosmos 1887 and 2044 biosatellites. Immunohistochemical (IHC)staining for the growth hormone-releasing factor (GRF), somatostatin (SS), and other hypothalamic hormones was performed on hypothalami obtained from rats. IHC analysis was complemented by quantitative in situ assessments of mRNAs encoding the precursors for these hormones. Data obtained suggest that exposure to microgravity causes a preferential reduction in GRF peptide and mRNA levels in hypophysiotropic neurons, which may contribute to impared GH secretion in animals subjected to spaceflight. Effects of weightlessness are not mimicked by hindlimb suspension in this system.

  15. Lateral Hypothalamic Stimulation Reduces Hyperalgesia Through Spinally Descending Orexin-A Neurons in Neuropathic Pain.

    Science.gov (United States)

    Wardach, Jacob; Wagner, Monica; Jeong, Younhee; Holden, Janean E

    2016-03-01

    No evidence to date shows that lateral hypothalamic (LH) stimulation produces orexin-A-mediated antinociception in the spinal cord dorsal horn (SCDH) in a model of neuropathic pain. We conducted experiments to examine the effect of orexin-A-mediated LH stimulation in female rats with chronic constriction injury (CCI) on thermal hyperalgesia. Rats receiving carbachol into the LH demonstrated antinociception on both the left CCI and right nonligated paws (p orexin-1 (OX1) receptor antagonist SB-334867, which blocked LH-induced antinociception compared with control groups (p orexin-A connection between the LH and the SCDH. Identification of this pathway may lead to studies using orexins to manage clinical pain.

  16. Effects of coal-burning type of fluorosis on hypothalamic-pituitary-ovary axis function in female rats%燃煤污染型氟中毒对雌鼠下丘脑-垂体-卵巢轴系统内分泌的影响

    Institute of Scientific and Technical Information of China (English)

    陈秀慧; 夏曙华; 余司文; 徐静峰; 喻茂娟; 王诚

    2015-01-01

    均无病理改变.光镜下,对照组雌鼠卵巢组织结构形态正常,均可见多个黄体及不同发育阶段的卵泡,颗粒细胞呈单层或多层整齐排列;染氟组雌鼠卵巢间质细胞、颗粒细胞呈高度水肿,卵泡退化增多,成熟卵泡偶见,细胞结构和细胞轮廓变得模糊不清.电镜下,对照组卵巢颗粒细胞超微结构正常,细胞核呈圆形,核内染色质均匀分布,胞质内含有丰富的线粒体及内质网,且形态正常;染氟组卵巢颗粒细胞及间质细胞出现凋亡特征,如核仁消失、线粒体肿胀、染色质在核膜聚集.结论 氟可促使卵巢组织凋亡,破坏微环境,致使卵巢分泌的P、INH减少,下丘脑GnRH和垂体FSH、LH增高,使性腺轴系统分泌异常;氟影响雌鼠性腺轴的部位可能不是下丘脑、垂体,而是卵巢.%Objective To observe the influence of coal-burning type of fluorosis on hypothalamic-pituitaryovary axis function and to explore possible mechanism in female rats.Methods Sixty SD rats were divided into two groups according to body weight with the method of random number table:control group and fluorosis group,30 rats in each group.Fluorosis group was feed with corn powder baked by high fluorine coal from Zhijin area.Changes of female rats' teeth during fluorine exposure were observed.After feeding for 180 days,24 h urine was collected in estrus and fluorine level was tested using fluoride ion-selective electrode; rats were executed and bone fluorine level was tested with high-temperature ashing-fluorine ion-selective electrode.Femoral artery blood was collected and serum was separated to test the contents of follicle stimulating hormone (FSH),luteinizing hormone (LH),testosterone (T),estradiol (E2) and progesterone (P) with electrochemiluminescence radioimmunoassay and gonadotropin-releasing hormone (GnRH),inhibin (INH) with enzyme-linked immunosorbent assay (ELISA),respectively.Organs,including hypothalamus,pituitary gland and ovary were

  17. [The function of the oxytocin-synthesizing system of the hypothalamus in rats with diabetes mellitus undergoing hypoxic training].

    Science.gov (United States)

    Kolesnyk, Iu M; Abramov, A V; Trzhetsyns'kyĭ, S D; Hancheva, O V

    1999-01-01

    The state of hypothalamic oxytocin-synthesizing system in Wistar rats were investigating. The morphometric measurements and immunocytochemical detection of oxytocin-containing cells was used for determining of the functional state of supraoptic nucleus, anterior and posterior-medialis magnocellular subdivisions of paraventricular nucleus. It was established intermittent hypoxic training exert positive influence on rats with experimental diabetes mellitus. This effects depending on increasing synthesis and secretion of hypothalamic oxytocin. Intermittent hypoxic training elevate conte