scholarly journals Orexin A suppresses in vivo GH secretion

2004 ◽  
pp. 731-736 ◽  
Author(s):  
LM Seoane ◽  
SA Tovar ◽  
D Perez ◽  
F Mallo ◽  
M Lopez ◽  
...  
Keyword(s):  
Nutritional Status ◽  
Area Under The Curve ◽  
Sleep Regulation ◽  
Gh Secretion ◽  
Neuroendocrine Function ◽  
Freely Moving Rats ◽  
Freely Moving ◽  
The Brain

BACKGROUND/AIMS: Orexins (OXs) are a newly described family of hypothalamic neuropeptides. Based on the distribution of OX neurons and their receptors in the brain, it has been postulated that they could play a role in the regulation of neuroendocrine function. GH secretion is markedly influenced by nutritional status and body weight. To investigate the role OX-A plays in the neuroregulation of GH secretion we have studied its effect on spontaneous GH secretion as well as GH responses to GHRH and ghrelin in freely moving rats. Finally, we also assessed the effect of OX-A on in vitro GH secretion. METHODS: We administered OX-A (10 microg, i.c.v.) or vehicle (10 microl, i.c.v.) to freely moving rats. Spontaneous GH secretion was assessed over 6 h with blood samples taken every 15 min. RESULTS: Administration of OX-A led to a decrease in spontaneous GH secretion in comparison with vehicle-treated rats, as assessed by mean GH levels (means+/-s.e.m. 4.2+/-1.7 ng/ml vs 9.4+/-2.2 ng/ml; P<0.05), mean GH amplitude (3.6+/-0.5 ng/ml vs 20.8+/-5.6 ng/ml; P<0.01) and area under the curve (848+/-379 ng/ml per 4 h vs 1957+/-458 ng/ml per 4 h; P<0.05). In contrast, OX-A failed to modify in vivo GH responses to GHRH (10 microg/kg, i.v.) although it markedly blunted GH responses to ghrelin (40 microg/kg, i.v.) (mean peak GH levels: 331+/-71 ng/ml, vehicle, vs 43+/-11 ng/ml in OX-A-treated rats; P<0.01). Finally, OX-A infusion (10(-7), 10(-8) or 10(-9) M) failed to modify in vitro basal GH secretion or GH responses to GHRH, ghrelin and KCl. CONCLUSIONS: These data indicate that OX-A plays an inhibitory role in GH secretion and may act as a bridge among the regulatory signals that are involved in the control of growth, nutritional status and sleep regulation.

scholarly journals Ghrelin elicits a marked stimulatory effect on GH secretion in freely-moving rats

2000 ◽  
pp. R7-R9 ◽  
Author(s):  
LM Seoane ◽  
S Tovar ◽  
R Baldelli ◽  
E Arvat ◽  
E Ghigo ◽  
...  
Keyword(s):  
Physiological Control ◽  
Gh Secretion ◽  
Freely Moving Rats ◽  
Anaesthetized Rats ◽  
Freely Moving ◽  
The One ◽  
Plasma Gh ◽  
Different Doses

Ghrelin is a growth hormone-releasing acylated peptide from stomach. The purified peptide consist of 28 amino acids in which the serine 3 residue is n-octanoylated. Ghrelin has been reported to increase in vitro GH secretion as well as in vivo plasma GH levels in pentobarbital anaesthetized rats. The aim of this work was to characterize the stimulatory effect of Ghrelin on in vivo GH secretion in freely-moving rats. Furthermore, we compare the effect of Ghrelin with GHRH. In addition to vehicle, we administered different doses of Ghrelin (3 nmol/Kg, 12 nmol/Kg and 60 nmol/Kg); GHRH (3 nmol/Kg and 12 nmol/kg). Plasma GH levels were measured in blood samples taken at 5, 10, 15, 20, 30 and 45 min after their administration as an i.v. bolus at 0 min. Administration of Ghrelin led to an increase in plasma GH levels at all time-points tested (5, 10, 15, 20 and 30 min, P<0.01; and 45 min, P<0.05) in comparison to control untreated rats. A maximal stimulatory effect on plasma GH was observed following administration of 12 nmol/Kg of Ghrelin, the effect being similar to the one obtained with 60 nmol/Kg in terms of both AUC and mean peak GH levels. At the dose of 3 nmol/Kg GHRH and Ghrelin exhibited a similar stimulatory effect in term of both, AUC and mean peak GH levels. However following administration of a dose of 12 nmol/Kg, the effect of Ghrelin was much greater than the same dose of GHRH in terms of both AUC and mean peak GH levels. In summary, this study provides the first evidences that Ghrelin exert a marked stimulatory effect in plasma GH levels in freely-moving rats and provides further evidences that Ghrelin may play an important role in the physiological control of GH secretion.

scholarly journals Obestatin Partially Affects Ghrelin Stimulation of Food Intake and Growth Hormone Secretion in Rodents

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1648-1653 ◽  
Author(s):  
Philippe Zizzari ◽  
Romaine Longchamps ◽  
Jacques Epelbaum ◽  
Marie Thérèse Bluet-Pajot
Keyword(s):  
Food Intake ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Male Rats ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Freely Moving ◽  
Stimulation Of

Administration of ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHSR 1a), induces potent stimulating effects on GH secretion and food intake. However, more than 7 yr after its discovery, the role of endogenous ghrelin remains elusive. Recently, a second peptide, obestatin, also generated from proteolytic cleavage of preproghrelin has been identified. This peptide inhibits food intake and gastrointestinal motility but does not modify in vitro GH release from pituitary cells. In this study, we have reinvestigated obestatin functions by measuring plasma ghrelin and obestatin levels in a period of spontaneous feeding in ad libitum-fed and 24-h fasted mice. Whereas fasting resulted in elevated ghrelin levels, obestatin levels were significantly reduced. Exogenous obestatin per se did not modify food intake in fasted and fed mice. However, it inhibited ghrelin orexigenic effect that were evident in fed mice only. The effects of obestatin on GH secretion were monitored in superfused pituitary explants and in freely moving rats. Obestatin was only effective in vivo to inhibit ghrelin stimulation of GH levels. Finally, the relationship between octanoylated ghrelin, obestatin, and GH secretions was evaluated by iterative blood sampling every 20 min during 6 h in freely moving adult male rats. The half-life of exogenous obestatin (10 μg iv) in plasma was about 22 min. Plasma obestatin levels exhibited an ultradian pulsatility with a frequency slightly lower than octanoylated ghrelin and GH. Ghrelin and obestatin levels were not strictly correlated. In conclusion, these results show that obestatin, like ghrelin, is secreted in a pulsatile manner and that in some conditions; obestatin can modulate exogenous ghrelin action. It remains to be determined whether obestatin modulates endogenous ghrelin actions.

scholarly journals Injectable Nanoelectrodes Enable Wireless Deep Brain Stimulation of Native Tissue in Freely Moving Mice

2020 ◽  
Author(s):  
Kristen L. Kozielski ◽  
Ali Jahanshahi ◽  
Hunter B. Gilbert ◽  
Yan Yu ◽  
Önder Erin ◽  
...  
Keyword(s):  
Behavioral Changes ◽  
Less Invasive ◽  
Magnetoelectric Materials ◽  
The Central Nervous System ◽  
Freely Moving ◽  
The Brain ◽  
Deep Brain ◽  
Stimulation Of

AbstractDevices that electrically modulate the central nervous system have enabled important breakthroughs in the management of neurological and psychiatric disorders. Such devices typically have centimeter-scale dimensions, requiring surgical implantation and wired-in powering. Using smaller, remotely powered materials could lead to less invasive neuromodulation. Herein, we present injectable magnetoelectric nanoelectrodes that wirelessly transmit electrical signals to the brain in response to an external magnetic field. Importantly, this mechanism of modulation requires no genetic modification of the brain, and allows animals to freely move during stimulation. Using these nanoelectrodes, we demonstrate neuronal modulation in vitro and in deep brain targets in vivo. We also show that local thalamic modulation promotes modulation in other regions connected via basal ganglia circuitry, leading to behavioral changes in mice. Magnetoelectric materials present a versatile platform technology for less invasive, deep brain neuromodulation.

Flexible intravenous microdialysis probe for blood sampling in freely moving rats

1993 ◽  
Vol 74 (1) ◽  
pp. 466-469 ◽  
Author(s):  
P. Rada ◽  
M. Parada ◽  
L. Hernandez
Keyword(s):  
Blood Sampling ◽  
In Vitro Tests ◽  
Microdialysis Probe ◽  
Freely Moving Rats ◽  
Intravenous Microdialysis ◽  
Silastic Tubing ◽  
Freely Moving ◽  
Circulating Levels

A flexible intravenous microdialysis probe was constructed from Silastic tubing (0.5 mm ID and 1.0 mm OD), with a cellulose hollow fiber tip 0.2 mm in diameter and 25 mm long with a 6,000 mol wt cut off. In vitro tests showed relative recovery rates of 39.1 +/- 1.9% for epinephrine. In vivo tests in freely moving rats, 36 h and 7 days after surgery, showed stable amounts of epinephrine and glucose. After intraperitoneal injections of 2-deoxy-D-glucose, circulating levels of epinephrine and glucose increased significantly. Similar results were obtained several days after implantation of the probe. We conclude that in situations where prolonged blood sampling is necessary, the flexible microdialysis probe provides a reliable means of accessing circulating levels of neuroactive compounds, nutrients, metabolites, and drugs.

scholarly journals AANAT1 functions in astrocytes to regulate sleep homeostasis

2019 ◽  
Author(s):  
Sejal Davla ◽  
Gregory Artiushin ◽  
Daryan Chitsaz ◽  
Sally Li ◽  
Amita Sehgal ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Critical Role ◽  
Cholinergic Neurons ◽  
Adult Brain ◽  
List Type ◽  
Sleep Regulation ◽  
Control Functions ◽  
The Brain

SummaryCharacteristic features of sleep are conserved among species [1], and from humans to insects sleep is influenced by neural circuits involving monoamines such as serotonin and dopamine [2]. Glial cells have been increasingly implicated in mechanisms of baseline and homeostatic sleep regulation in mammals and flies [3–11], but it remains unknown whether and how glia might influence monoaminergic control of sleep. Sleep is regulated by circadian rhythms and a homeostatic drive to compensate for prolonged wakefulness, and growing evidence suggests that neural mechanisms controlling homeostatic sleep can be discriminated from those controlling baseline sleep [12–15]. In Drosophila, mutants of arylalkylamine N-acetyltransferase 1 (AANAT1lo) have normal baseline amounts of sleep and motor activity, but increased rebound sleep following deprivation [16]. AANAT1 can acetylate and inactivate monoamines in vitro [17], but the role of AANAT1 in vivo remains poorly understood. We find AANAT1 to be expressed in astrocytes and subsets of neurons in the adult Drosophila brain, with levels in astrocytes declining markedly overnight. In sleep-deprived AANAT1 mutant flies, heightened rebound sleep is accompanied by increased serotonin and dopamine levels in the brain. In neurons, AANAT1 functions to limit the quantity and consolidation of nighttime sleep, but in astrocytes AANAT1 constrains the amount of rebound sleep that flies take in response to sleep deprivation. These findings distinguish sleep-control functions of AANAT1 in neurons and astrocytes, and identify a critical role for astrocytes in the regulation of monoamine bioavailability and calibration of the response to sleep need.HighlightsThe monoamine catabolic enzyme arylalkylamine N-acetyltransferase 1 (AANAT1) is expressed by astrocytes and subsets of serotonergic, glutamatergic, GABAergic and cholinergic neurons in the adult brain of Drosophila.AANAT1 limits accumulation of serotonin and dopamine in the brain upon sleep deprivation.Loss of AANAT1 from astrocytes, but not from neurons, causes flies to increase their daytime rebound sleep in response to overnight sleep deprivation.

scholarly journals Leptin increases in vivo GH responses to GHRH and GH-releasing peptide-6 in food-deprived rats

2000 ◽  
pp. 66-70 ◽  
Author(s):  
E Carro ◽  
LM Seoane ◽  
R Senaris ◽  
FF Casanueva ◽  
C Dieguez
Keyword(s):  
Marked Decrease ◽  
Area Under The Curve ◽  
Test Results ◽  
Maximal Dose ◽  
Primary Defect ◽  
Gh Secretion ◽  
Freely Moving ◽  
Ad Libitum ◽  
Fasted Rats

BACKGROUND: Leptin has recently been shown to have a stimulatory effect on basal GH secretion. However, the mechanisms by which leptin exert this effect are not yet clear. GHRH and GH-releasing peptide (GHRP)-6 are the two most potent GH secretagogues described to date. OBJECTIVE: To determine if leptin could also enhance in vivo GH responses to a maximal dose of GHRH. DESIGN: Leptin (10microg i.c.v.) or vehicle was administered at random before GHRH (10microg/kg i,v.) or GHRP-6 (50microg/kg i.v.), to freely-moving rats with food available ad libitum and to (48h) food-deprived rats. METHODS: Leptin and GH concentrations were measured by radioimmunoassay. Comparison between the different groups was assessed by the Mann-Whitney test. RESULTS: In comparison with fed rats, food-deprived rats showed a marked decrease in GH responses to GHRH as assessed by the area under the curve (5492+/-190ng/ml in fed rats and 1940+/-128ng/ml in fasted rats; P<0.05) and GHRP-6 (3695+/-450 in fed rats and 1432+/-229 in fasted rats; P<0.05). In comparison with its effects in vehicle-treated rats, leptin administered to food-deprived rats markedly increased GH responses to both GHRH (6625+/-613ng/ml; P<0.05) and GHRP-6 (5862+/-441ng/ml; P<0.05). CONCLUSIONS: These data suggest that the blunted GH response to GHRH and GHRP-6 in food-deprived rats is a functional and reversible state, and that the decreased leptin concentrations could be the primary defect responsible for the altered GH secretion in food-deprived rats.

scholarly journals Nonresonant powering of injectable nanoelectrodes enables wireless deep brain stimulation in freely moving mice

2021 ◽  
Vol 7 (3) ◽  
pp. eabc4189
Author(s):  
K. L. Kozielski ◽  
A. Jahanshahi ◽  
H. B. Gilbert ◽  
Y. Yu ◽  
Ö. Erin ◽  
...  
Keyword(s):  
Neural Tissue ◽  
Behavioral Changes ◽  
Less Invasive ◽  
Magnetoelectric Materials ◽  
Freely Moving ◽  
Risk Of Hemorrhage ◽  
The Brain ◽  
Deep Brain

Devices that electrically modulate the deep brain have enabled important breakthroughs in the management of neurological and psychiatric disorders. Such devices are typically centimeter-scale, requiring surgical implantation and wired-in powering, which increases the risk of hemorrhage, infection, and damage during daily activity. Using smaller, remotely powered materials could lead to less invasive neuromodulation. Here, we present injectable, magnetoelectric nanoelectrodes that wirelessly transmit electrical signals to the brain in response to an external magnetic field. This mechanism of modulation requires no genetic modification of neural tissue, allows animals to freely move during stimulation, and uses nonresonant carrier frequencies. Using these nanoelectrodes, we demonstrate neuronal modulation in vitro and in deep brain targets in vivo. We also show that local subthalamic modulation promotes modulation in other regions connected via basal ganglia circuitry, leading to behavioral changes in mice. Magnetoelectric materials present a versatile platform technology for less invasive, deep brain neuromodulation.

Honokiol and Magnolol Increased Hippocampal Acetylcholine Release in Freely-Moving Rats

2000 ◽  
Vol 28 (03n04) ◽  
pp. 379-384 ◽  
Author(s):  
Yu-Chi Hou ◽  
Pei-Dawn Lee Chao ◽  
Shiouh-Yi Chen
Keyword(s):  
Acetylcholine Release ◽  
Stem Bark ◽  
High Dose ◽  
M 10 ◽  
Freely Moving Rats ◽  
Freely Moving ◽  
Magnolia Officinalis ◽  
Choline Acetyltransferase Activity

Honokiol and magnolol, phenolic compounds isolated from the stem bark of Magnolia officinalis, have been demonstrated to increase choline acetyltransferase activity, inhibit acetylcholinesterase, promote potassium-induced acetylcholine release and exhibit neurotrophic function in in vitro studies. The objective of the present study was to determine the effect of these compounds on hippocampal acetylcholine release in conscious, freely-moving rats. 10-4 M–10-6 M of honokiol or magnolol was perfused into rat hippocampus via a dialysis probe. The results showed that at 10-4 M concentration, honokiol and magnolol markedly increased extracellular acetylcholine release to 165.5 ± 5.78% and 237.83 ± 9.47% of the basal level, respectively. However, lower concentrations of either compounds failed to elicit significant acetylcholine release. This result suggests that a high dose of honokiol or magnolol may enhance in vivo hippocampal acetylcholine release.

Model-projected mechanistic bases for sex differences in growth hormone regulation in humans

2007 ◽  
Vol 292 (4) ◽  
pp. R1577-R1593 ◽  
Author(s):  
Leon S. Farhy ◽  
Cyril Y. Bowers ◽  
Johannes D. Veldhuis
Keyword(s):  
Growth Hormone ◽  
Model Structure ◽  
Hormone Regulation ◽  
Gh Secretion ◽  
Proposed Model ◽  
Physiol Regul Integr Comp ◽  
Model Platform ◽  
The Brain

Models of physiological systems facilitate rational experimental design, inference, and prediction. A recent construct of regulated growth hormone (GH) secretion interlinks the actions of GH-releasing hormone (GHRH), somatostatin (SRIF), and GH secretagogues (GHS) with GH feedback in the rat (Farhy LS, Veldhuis JD. Am J Physiol Regul Integr Comp Physiol 288: R1649–R1663, 2005). In contrast, no comparable formalism exists to explicate GH dynamics in any other species. The present analyses explore whether a unifying model structure can represent species- and sex-defined distinctions in the human and rodent. The consensus principle that GHRH and GHS synergize in vivo but not in vitro was explicable by assuming that GHS 1) evokes GHRH release from the brain, 2) opposes inhibition by SRIF both in the hypothalamus and on the pituitary gland, and 3) stimulates pituitary GH release directly and additively with GHRH. The gender-selective principle that GH pulses are larger and more irregular in women than men was conferrable by way of 4) higher GHRH potency and 5) greater GHS efficacy. The overall construct predicts GHRH/GHS synergy in the human only in the presence of SRIF when the brain-pituitary nexus is intact, larger and more irregular GH pulses in women, and observed gender differences in feedback by GH and the single and paired actions of GHRH, GHS, and SRIF. The proposed model platform should enhance the framing and interpretation of novel clinical hypotheses and create a basis for interspecies generalization of GH-axis regulation.

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