scholarly journals TRAPing Ghrelin-Activated Circuits: A Novel Tool to Identify, Target and Control Hormone-Responsive Populations in TRAP2 Mice

2022 ◽  
Vol 23 (1) ◽  
pp. 559
Author(s):  
Iris Stoltenborg ◽  
Fiona Peris-Sampedro ◽  
Erik Schéle ◽  
Marie V. Le May ◽  
Roger A. H. Adan ◽  
...  

The availability of Cre-based mouse lines for visualizing and targeting populations of hormone-sensitive cells has helped identify the neural circuitry driving hormone effects. However, these mice have limitations and may not even be available. For instance, the development of the first ghrelin receptor (Ghsr)-IRES-Cre model paved the way for using the Cre-lox system to identify and selectively manipulate ghrelin-responsive populations. The insertion of the IRES-Cre cassette, however, interfered with Ghsr expression, resulting in defective GHSR signaling and a pronounced phenotype in the homozygotes. As an alternative strategy to target ghrelin-responsive cells, we hereby utilize TRAP2 (targeted recombination in active populations) mice in which it is possible to gain genetic access to ghrelin-activated populations. In TRAP2 mice crossed with a reporter strain, we visualized ghrelin-activated cells and found, as expected, much activation in the arcuate nucleus (Arc). We then stimulated this population using a chemogenetic approach and found that this was sufficient to induce an orexigenic response of similar magnitude to that induced by peripheral ghrelin injection. The stimulation of this population also impacted food choice. Thus, the TRAPing of hormone-activated neurons (here exemplified by ghrelin-activated pathways) provides a complimentary/alternative technique to visualize, access and control discrete pathways, linking hormone action to circuit function.

1960 ◽  
Vol XXXIII (II) ◽  
pp. 230-250 ◽  
Author(s):  
Eileen E. Hill

ABSTRACT A method for the fractionation of the urinary 17-ketogenic steroids with no oxygen grouping at C11 and those oxygenated at C11, is applied to the clinical problems of congenital adrenal hyperplasia. In normal children the mean ratio of the non-oxygenated to oxygenated steroids is 0.24. In childrern with congenital adrenal hyperplasia the ratio is 2.3. The reason for this difference in ratio is discussed. The changes in ratio found under stimulation of the adrenal gland with exogenous or endogenous corticotrophin and the suppression with cortisone therapy are studied. This test can be applied to isolated samples of urine, a major advantage in paediatric practice, and can be carried out in routine laboratories. It is found to be reliable in the diagnosis and sensitive in the control of congenital adrenal hyperplasia.


2004 ◽  
Vol 287 (2) ◽  
pp. G425-G435 ◽  
Author(s):  
Harjot Sidhu ◽  
Mark Kern ◽  
Reza Shaker

Cerebral cortical activity associated with perceived visceral sensation represents registration of afferent transduction and cognitive processes related to perception. Abnormalities of gut sensory function can involve either or both of these processes. Cortical registration of subliminal viscerosensory signals represents cerebral cortical activity induced by stimulation of intestinal sensory neurocircuitry without the influence of perception-related cortical activity, whereas those associated with perception represent both neural circuitry and cognitive processes. Our aims were to determine and compare quantitatively cerebral cortical functional magnetic resonance imaging (fMRI) activity in response to subliminal, liminal, and nonpainful supraliminal rectal distension between a group of irritable bowel syndrome (IBS) patients and age/gender-matched controls. Eight female IBS patients and eight age-matched healthy female control subjects were studied using brain fMRI techniques. Three barostat-controlled distension levels were tested: 1) 10 mmHg below perception (subliminal), 2) at perception (liminal), and 3) 10 mmHg above perception (supraliminal). In control subjects, there was a direct relationship between stimulus intensity and cortical activity volumes, ie., the volume of fMRI cortical activity in response to subliminal (3,226 ± 335 μl), liminal (5,751 ± 396 μl), and supraliminal nonpainful stimulation (8,246 ± 624 μl) were significantly different ( P < 0.05). In contrast, in IBS patients this relationship was absent and fMRI activity volumes for subliminal (2,985 ± 332 μl), liminal (2,457 ± 342 μl), and supraliminal nonpainful stimulation (2,493 ± 351 μl) were similar. Additional recruitment of cortical fMRI activity volume in response to increasing stimulation from subliminal to liminal and supraliminal domains is absent in IBS patients, suggesting a difference in the processing of perceived stimulation compared with controls.


1990 ◽  
Vol 157 (6) ◽  
pp. 881-887 ◽  
Author(s):  
Paul Furlong ◽  
Paul Barczak ◽  
Gwilym Hayes ◽  
Graham Harding

The SSEPs obtained from 19 schizophrenics defined by RDC, DSM–III and PSE criteria Were compared with those from a control group of healthy volunteers. Previous findings of an abnormal lack of lateralising response in schizophrenic patients were not replicated. No significant difference in either amplitude or morphology between the traces obtained from the two groups were recorded. Ipsilateral and contralateral latencies for stimulation of the left and right index finger showed no significant difference in peak latency for any component between patient and control group. When mean peak-to-peak amplitudes were plotted the contralateral component was always greater in amplitude than the ipsilateral one. An objective measure of the degree of lateralisation, the percentage lateralisation quotient, showed no lateralisation differences between the patient and control groups. A case of myogenic contamination of ipsilateral components was observed calling into doubt findings where no temporal region monitoring has been performed.


Author(s):  
Thomas Guiho ◽  
Christine Azevedo Coste ◽  
Claire Delleci ◽  
Jean-Patrick Chenu ◽  
Jean-Rodolphe Vignes ◽  
...  

Spinal cord injuries (SCI) result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self-) catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session.


1991 ◽  
Vol 71 (1) ◽  
pp. 23-29 ◽  
Author(s):  
T. Izawa ◽  
T. Komabayashi ◽  
T. Mochizuki ◽  
K. Suda ◽  
M. Tsuboi

Digitonin-permeabilized adipocytes were used to study the coupling of adenylate cyclase (AC) to lipolysis in exercise-trained rats. Isoproterenol-(IPR) stimulated lipolysis in permeabilized cells was significantly greater in trained than in control rats. Under essentially identical conditions, the dose-response curve for IPR stimulation of AC activity in the absence of 3-isobutyl-1-methylxanthine was similar in trained and control rats. However, the potency of stimulation by IPR as a percentage of the basal level was greater in trained rats. AC activity and lipolysis in the presence of 3-isobutyl-1-methylxanthine were also significantly greater in trained than in control rats. Least-squares analysis by plotting the log AC vs. lipolysis values showed that the regression coefficient was about three-fold greater in trained than in control rats. The concentration of endogenous adenosine 3′,5′-cyclic monophosphate (cAMP) needed to produce a half-maximal lipolytic response was 18.58 and 10.81 pmol.min-1.10(6) cells-1 in control and trained rats, respectively. Thus a positive relationship existed between lipolysis and AC activity, with a tighter coupling in trained rats. Lipolysis in response to exogenous cAMP tended to be greater in trained than in control rats, and the difference was statistically significant for 50 microM and 10 mM cAMP. Our finding support the concept that the major mechanism of enhanced lipolysis in trained rats was an increase in the activity of enzymatic step(s) distal to cAMP.


1991 ◽  
Vol 155 (1) ◽  
pp. 455-467
Author(s):  
R. BRENT THOMSON ◽  
N. AUDSLEY ◽  
JOHN E. PHILLIPS

The commonly used method of passing short-circuit current (Isc) across insect epithelia through Ag-AgCl electrodes, without the use of salt bridges, leads to significant OH− production at the cathode (lumen side) when high currents are applied. The alkalization of the lumen previously reported when cyclic AMP was added to short-circuited locust hindgut is a result of this phenomenon rather than cyclic-AMP-mediated stimulation of acid-base transport in the hindgut. When salt bridges are used to pass short-circuit current across locust hindgut, acid secretion (JH) into the lumen equals alkaline movement (JOH) to the haemocoel side, and JH is similar under both open- and short-circuit conditions. JH is similar (1.5 μequiv cm−2 h−1) in recta and ilea. Addition of cyclic AMP inhibits JH across the rectum by 42–66%, but has no effect on the ileum when salt bridges are used. Electrical parameters (Isc, Vt, Rt) reflecting hindgut Cl− transport (JCL) before and after stimulation with cyclic AMP are the same whether or not salt bridges are used. We found no evidence of any coupling between JCl and JH/JOH.


2000 ◽  
Vol 6 (1) ◽  
pp. 55-64
Author(s):  
Hari Suprapto

The extra cellular product (ECP) was rapidly induced leucocyte number compared to Edwardseilla tarda NUF251 in eel blood. The reason could be live cells need time to multiplied in eel body whereas the ECP composed of high protein therefore induce the leucocyte production in short time. The number of leucocyte in eel blood were not different between inactivated ECP and control eels. Although the leucocyte number increased gradually in live cells injected eel but have not correlation to increasing phagocytosis index (PI) in vivo phagocytosis. The PI and phagocytic rate (PR) of in vivo phagocytosis relatively constant from 24-96 h post injection.


Author(s):  
Г.А. Дроздова ◽  
О.И. Линецкая ◽  
Е.А. Нургалеева ◽  
Э.И. Эткина ◽  
Э.Ф. Аглетдинов

Цель работы - изучить возможности патогенетической коррекции синбиотиком метаболических нарушений, вызванных чрезмерным потреблением жиров и оценить уровень лептина, грелина и их рецепторов. Методика. В работе использовалось второе поколение лабораторных крыс линии Вистар препубертатного возраста, находившихся на диете с избыточным содержанием жиров (51% от общего рациона). В возрасте 5 нед. в рацион экспериментальной подгруппы включали синбиотик, по достижению 7-недельного возраста животных выводили из эксперимента декапитацией с последующим забором материала для бактериологических, биохимических и иммуноферментных исследований. Результаты. Показано, что избыточное потребление жиров способствует росту условно-патогенной микробиоты, снижению содержания лакто- и бифидобактерий в толстом кишечнике и развитию дислипидемии. Наблюдается статистически значимое повышение уровня лептина в сыворотке крови на 49,9 %. В жировой ткани отмечено увеличение количества рецепторов к лептину ( в два раза) и грелину (на 28,2%). После коррекции синбиотиком положительная динамика отмечалась со стороны микробиоты, липидного профиля, снижался уровень лептина в сыворотке крови и рецепторов к грелину в жировой ткани. Заключение: синбиотик способствует нормализации микробиоты желудочно-кишечного тракта, липидного профиля и уровня пептидных гормонов, ответственных за чувство голода и насыщения. The aim of the study was to evaluate a possibility of using synbiotics for pathogenetic correction of metabolic disorders induced by excessive consumption of fat and to measure levels of leptin, ghrelin, and their receptors. Methods. Experiments were conducted on the second generation of prepubertal Wistar rats consuming a diet with excessive fat (51% of diet). A synbiotic was included into the diet of a rat group aged 5 weeks. At age of 7 weeks, animals of the experimental and control groups were decapitated and samples were taken for bacteriological, biochemical, and enzyme immunoassay studies. Results. Excessive fat consumption resulted in growth of conditionally pathogenic microbiota, decreased levels of lacto- and bifidobacteria in the large intestine and feces, and development of dyslipidemia. Also, serum level of leptin was increased by 49.9%, ghrelin receptor density in adipose tissue was increased by 28.2%, and leptin receptors density in adipose tissue was increased twofold. The synbiotic treatment resulted in beneficial changes of the microbiota and lipid profile; serum level of leptin and ghrelin receptors density in adipose tissue decreased. Conclusion: The synbiotic drug normalized the gastrointestinal microbiota, lipid profile, and peptide hormones responsible for feelings of hunger and satiety.


2016 ◽  
Vol 115 (2) ◽  
pp. 1043-1062 ◽  
Author(s):  
Arani Roy ◽  
Jason J. Osik ◽  
Neil J. Ritter ◽  
Shen Wang ◽  
James T. Shaw ◽  
...  

Many circuits in the mammalian brain are organized in a topographic or columnar manner. These circuits could be activated—in ways that reveal circuit function or restore function after disease—by an artificial stimulation system that is capable of independently driving local groups of neurons. Here we present a simple custom microscope called ProjectorScope 1 that incorporates off-the-shelf parts and a liquid crystal display (LCD) projector to stimulate surface brain regions that express channelrhodopsin-2 (ChR2). In principle, local optogenetic stimulation of the brain surface with optical projection systems might not produce local activation of a highly interconnected network like the cortex, because of potential stimulation of axons of passage or extended dendritic trees. However, here we demonstrate that the combination of virally mediated ChR2 expression levels and the light intensity of ProjectorScope 1 is capable of producing local spatial activation with a resolution of ∼200–300 μm. We use the system to examine the role of cortical activity in the experience-dependent emergence of motion selectivity in immature ferret visual cortex. We find that optogenetic cortical activation alone—without visual stimulation—is sufficient to produce increases in motion selectivity, suggesting the presence of a sharpening mechanism that does not require precise spatiotemporal activation of the visual system. These results demonstrate that optogenetic stimulation can sculpt the developing brain.


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