The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Alastair V. Ferguson - One of the best experts on this subject based on the ideXlab platform.
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The transcriptome of the rat subfornical Organ is altered in response to early postnatal overnutrition.
IBRO Reports, 2018Co-Authors: Colleen S. Peterson, Shuo Huang, Alastair V. FergusonAbstract:Abstract Early postnatal overnutrition in humans is associated with long-term negative outcomes including obesity, increased risk of type-II diabetes, and cardiovascular disease. Hypothalamic neurons from rodents exposed to early postnatal overnutrition show altered expression of satiety signals and receptors, and exhibit altered responses to many satiety signals, suggesting a hypothalamic link between early overnutrition and development of these sequelae. Importantly, several hypothalamic nuclei receive information regarding circulating hormones (such as insulin, leptin and ghrelin) from the subfornical Organ (SFO), a forebrain sensory Circumventricular Organ which lacks a blood brain barrier. Previous transcriptomic studies indicate that challenges to energy balance and hydration status stimulate changes in gene expression within the SFO, including genes encoding ion channels and receptors. In order to determine if early postnatal overnutrition also causes changes in SFO gene expression which may be associated with homeostatic dysregulation, we performed whole transcriptome sequencing on SFO tissue from rats raised in small (4 pups), or control (large, 12 pups) litters. Illumina RNA sequencing was performed on SFO tissue from rats raised from small and large litters, and read sequences were aligned to the Rat Rnor_6.0 genome. Control data were further compared to previously published microarray data set for validation. We found statistically significant (p
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Behavioral/Systems/Cognitive Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin
2016Co-Authors: Alastair V. FergusonAbstract:Adiponectin is an adipocyte-derived peptide hormone involved in energy homeostasis and the pathogenesis of obesity, including hyper-tension. Area postrema (AP) lacks a blood–brain barrier and is a critical homeostatic integration center for humoral and neural signals. Here we investigate the role of AP in adiponectin signaling. We show that rat AP expresses AdipoR1 and AdipoR2 adiponectin receptor mRNA. We used current-clamp electrophysiology to investigate whether adiponectin influenced membrane properties of AP neurons and found that60 % of rat AP neurons tested were sensitive to adiponectin. Additional electrophysiology experiments coupled with single-cell reverse transcription-PCR indicated that all neurons that expressed both subtypes of receptor were sensitive to adiponectin, whereas neurons expressing only one subtype were predominantly insensitive. Last, microinjection of adiponectin into AP caused significant increases in arterial blood pressure, with no change in heart rate, suggesting that adiponectin acts at AP to provide a possible link between control of energy homeostasis and cardiovascular function. Key words: adiponectin; area postrema; Circumventricular Organ; patch clamp; microinjection; homeostasi
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Behavioral/Systems/Cognitive The Subfornical Organ: A Central Target for Circulating Feeding Signals
2016Co-Authors: Katherine J. Pulman, Mark W. Fry, Trevor G. Cottrell, Alastair V. FergusonAbstract:The mechanisms through which circulating ghrelin relays hunger signals to the CNS are not yet fully understood. In this study, we have examined the potential role of the subfornical Organ (SFO), a Circumventricular structure that lacks the normal blood–brain barrier, as a CNS site in which ghrelin acts to influence the hypothalamic centers controlling food intake.We report that ghrelin increased intracel-lular calcium concentrations in 28 % (12 of 43) of dissociated SFO neurons and that the SFO expresses mRNA for the growth hormone secretagogue receptor. Whole-cell patch recordings from SFO neurons demonstrated that in 29 % (9 of 31) of neurons tested ghrelin induced a mean depolarization of 7.4 0.69 mV, accompanied by an increase in action potential frequency. Voltage-clamp recordings revealed that ghrelin activates a putative nonselective cationic conductance. Previous reports that the satiety signal amylin exerts similar excitatory effects on SFO neurons led us to examine whether these two peptides influence different subpopulations of SFO neurons. Concentration-dependent depolarizing effects of amylin were observed in 59 % (28 of 47) of SFO neurons (mean depolarization, 8.32 0.60 mV). In contrast to ghrelin, voltage-clamp recordings suggest that amylin influences a voltage-dependent current activated at depolarized potentials.We tested single SFO neurons with both peptides and identified cells responsive only to ghrelin (n 9) and only to amylin (n 7) but no cells that responded to both peptides. These data support a role for the SFO as a center at which ghrelin and amylin may influence separate subpopulations of neurons to influence the hypothalamic regulation of feeding. Key words: ghrelin; amylin; subfornical Organ; Circumventricular Organ; electrophysiology; feedin
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Leptin influences the excitability of area postrema neurons
American journal of physiology. Regulatory integrative and comparative physiology, 2015Co-Authors: Pauline M. Smith, Paulina Brzezinska, Fabien Hubert, Andrea Mimee, Donald H. Maurice, Alastair V. FergusonAbstract:The area postrema (AP) is a Circumventricular Organ with important roles in central autonomic regulation. This medullary structure has been shown to express the leptin receptor and has been suggest...
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the transcriptome of the medullary area postrema the thirsty rat the hungry rat and the hypertensive rat
Experimental Physiology, 2011Co-Authors: Charles Hindmarch, Alastair V. Ferguson, Pauline M. Smith, Mark Fry, Song T Yao, Georgina G J Hazell, Stephen J Lolait, Julian F R Paton, David MurphyAbstract:The area postrema (AP) is a sensory Circumventricular Organ characterized by extensive fenestrated vasculature and neurons which are capable of detecting circulating signals of osmotic, cardiovascular, immune and metabolic status. The AP can communicate these messages via efferent projections to brainstem and hypothalamic structures that are able to orchestrate an appropriate response. We have used microarrays to profile the transcriptome of the AP in the Sprague–Dawley (SD) and Wistar–Kyoto rat and present here a comprehensive catalogue of gene expression, focusing specifically on the population of ion channels, receptors and G protein-coupled receptors expressed in this sensory tissue; of the G protein-coupled receptors expressed in the rat AP, we identified ∼36% that are orphans, having no established ligand. We have also looked at the ways in which the AP transcriptome responds to the physiological stressors of 72 h dehydration (DSD) and 48 h fasting (FSD) and have performed microarrays in these conditions. Comparison between the DSD and SD or between FSD and SD revealed only a modest number of AP genes that are regulated by these homeostatic challenges. The expression levels of a much larger number of genes are altered in the spontaneously hypertensive rat AP compared with the normotensive Wistar–Kyoto control rat, however. Finally, analysis of these ‘hypertension-related’ elements revealed genes that are involved in the regulation of both blood pressure and immune function and as such are excellent targets for further study.
Gabriel Viennet - One of the best experts on this subject based on the ideXlab platform.
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chordoid gliomas of the third ventricle share ttf 1 expression with Organum vasculosum of the lamina terminalis
The American Journal of Surgical Pathology, 2015Co-Authors: Franck Bielle, Chiara Villa, Marine Giry, A M Bergemerfouquet, Marc Polivka, Alexandre Vasiljevic, Mariehelene Aubriotlorton, Michele Bernier, Emmanuele Lechaptzalcman, Gabriel ViennetAbstract:Chordoid glioma of the third ventricle (CG3V) is a rare tumor developing in a stereotyped localization. It has been related to the Circumventricular Organ of the lamina terminalis, in the anterior part of the third ventricle, but its oncogenesis is poorly understood. TTF-1 transcription factor is in
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chordoid gliomas of the third ventricle share ttf 1 expression with Organum vasculosum of the lamina terminalis
The American Journal of Surgical Pathology, 2015Co-Authors: Franck Bielle, Chiara Villa, Marine Giry, A M Bergemerfouquet, Marc Polivka, Alexandre Vasiljevic, Mariehelene Aubriotlorton, Michele Bernier, Emmanuele Lechaptzalcman, Gabriel ViennetAbstract:Chordoid glioma of the third ventricle (CG3V) is a rare tumor developing in a stereotyped localization. It has been related to the Circumventricular Organ of the lamina terminalis, in the anterior part of the third ventricle, but its oncogenesis is poorly understood. TTF-1 transcription factor is involved in the development and adult physiology of the ventral forebrain. We studied the histopathologic and immunohistochemical features of a multicentric series of 17 cases of CG3V. We described additional histologic patterns (solid, fibrosing, and fusiform) to the typical chordoid pattern. TTF-1 was constantly expressed in CG3V, as in developing and adult lamina terminalis. The anti-TTF-1 SPT24 clone was more sensitive than the 8G7G3/1 clone. No mutation of IDH1 R132, IDH2 R172, or BRAF V600 codons was found. We showed TTF-1 as a useful marker for the diagnosis of CG3V and the understanding of its oncogenesis.
Song T Yao - One of the best experts on this subject based on the ideXlab platform.
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in renovascular hypertension tnf α type 1 receptors in the area postrema mediate increases in cardiac and renal sympathetic nerve activity and blood pressure
Cardiovascular Research, 2019Co-Authors: Song T Yao, Willian S Korim, Khalid Elsaafien, Jeremy R Basser, Anthony Setiadi, Clive N MayAbstract:AIMS Neuroinflammation is a common feature in renovascular, obesity-related, and angiotensin II mediated hypertension. There is evidence that increased release of the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α) contributes to the development of the hypertension, but the underlying neural mechanisms are unclear. Here, we investigated whether TNF-α stimulates neurons in the area postrema (AP), a Circumventricular Organ, to elicit sympathetic excitation, and increases in blood pressure (BP). METHODS AND RESULTS In rats with renovascular hypertension, AP neurons that expressed TNF-α type-1 receptor (TNFR1) remained constantly activated (expressed c-Fos) and injection of TNFR1 neutralizing antibody into the AP returned BP (systolic: ∼151 mmHg) to normotensive levels (systolic: ∼108 mmHg). Nanoinjection of TNF-α (100 pg/50 nL) into the AP of anaesthetized normotensive rats increased BP (∼16 mmHg) and sympathetic nerve activity, predominantly to the heart (∼53%), but also to the kidneys (∼35%). These responses were abolished by prior injection of a TNFR1 neutralizing antibody (1 ng/50 nL) within the same site. TNFR1 were expressed in the somata of neurons activated by TNF-α that were retrogradely labelled from the rostral ventrolateral medulla (RVLM). CONCLUSION These findings indicate that in renovascular hypertension, blocking TNFR1 receptors in the AP significantly reduces BP, while activation of TNFR1 expressing neurons in the AP by TNF-α increases BP in normotensive rats. This is mediated, in part, by projections to the RVLM and an increase in both cardiac and renal sympathetic nerve activity. These findings support the notion that proinflammatory cytokines and neuroinflammation are important pathological mechanisms in the development and maintenance of hypertension.
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the transcriptome of the medullary area postrema the thirsty rat the hungry rat and the hypertensive rat
Experimental Physiology, 2011Co-Authors: Charles Hindmarch, Alastair V. Ferguson, Pauline M. Smith, Mark Fry, Song T Yao, Georgina G J Hazell, Stephen J Lolait, Julian F R Paton, David MurphyAbstract:The area postrema (AP) is a sensory Circumventricular Organ characterized by extensive fenestrated vasculature and neurons which are capable of detecting circulating signals of osmotic, cardiovascular, immune and metabolic status. The AP can communicate these messages via efferent projections to brainstem and hypothalamic structures that are able to orchestrate an appropriate response. We have used microarrays to profile the transcriptome of the AP in the Sprague–Dawley (SD) and Wistar–Kyoto rat and present here a comprehensive catalogue of gene expression, focusing specifically on the population of ion channels, receptors and G protein-coupled receptors expressed in this sensory tissue; of the G protein-coupled receptors expressed in the rat AP, we identified ∼36% that are orphans, having no established ligand. We have also looked at the ways in which the AP transcriptome responds to the physiological stressors of 72 h dehydration (DSD) and 48 h fasting (FSD) and have performed microarrays in these conditions. Comparison between the DSD and SD or between FSD and SD revealed only a modest number of AP genes that are regulated by these homeostatic challenges. The expression levels of a much larger number of genes are altered in the spontaneously hypertensive rat AP compared with the normotensive Wistar–Kyoto control rat, however. Finally, analysis of these ‘hypertension-related’ elements revealed genes that are involved in the regulation of both blood pressure and immune function and as such are excellent targets for further study.
Andrew J. Lawrence - One of the best experts on this subject based on the ideXlab platform.
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The subfornical Organ in sodium appetite: Recent insights
Neuropharmacology, 2018Co-Authors: Andrew J. LawrenceAbstract:To maintain sodium homeostasis, animals will readily seek and ingest salt when salt-depleted, even at concentrations that they typically find aversive when sodium replete. This innate behaviour is known as sodium (or salt) appetite. Salt appetite is subserved by a conserved brain network that senses sodium need and promotes the ingestion of salty substances when sodium-deficient. The subfornical Organ (SFO) is a Circumventricular Organ that has diverse roles encompassing cardiovascular regulation, energy balance, immune responses, reproduction, and hydromineral balance. The SFO acts as a central sensor of sodium need and is essential for the generation of salt appetite. In this review, we discuss recent findings on the neurochemical and circuit-level Organisation of the SFO in the context of sodium appetite. This article is part of the Special Issue entitled 'Hypothalamic Control of Homeostasis'.
Rüdiger Gerstberger - One of the best experts on this subject based on the ideXlab platform.
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Astrocytes in sensory Circumventricular Organs of the rat brain express functional binding sites for endothelin
Neuroscience, 2000Co-Authors: E Gebke, Andreas Müller, Ulrich Pehl, Rüdiger GerstbergerAbstract:Abstract Sensory Circumventricular Organs bordering the anterior third cerebral ventricle, the subfornical Organ and the Organum vasculosum laminae terminalis, lack blood–brain barrier characteristics and are therefore accessible to circulating peptides like endothelins. Astrocytes of the rat subfornical Organ and Organum vasculosum laminae terminalis additionally showed immunocytochemical localization of endothelin-1/endothelin-3-like peptides, possibly acting as Circumventricular Organ-intrinsic modulators. Employing [ 125 I]endothelin-1 as radioligand, quantitative autoradiography demonstrated specific binding sites throughout the rat Organum vasculosum laminae terminalis and subfornical Organ, and competitive displacement studies revealed expression of both ET A and ET B receptor subtypes for either Circumventricular Organ. ET B receptor binding prevailed for the whole brain and ET A receptors could be labelled in the peripheral vascular system. To characterize endothelin-specific receptors in astrocytes of both Circumventricular Organs, alterations in the intracellular calcium concentration due to endothelin-1/endothelin-3 stimulation were studied in primary culture of subfornical Organ and Organum vasculosum laminae terminalis cells obtained from early postnatal rat pups. Endothelin-1 and endothelin-3 induced Ca 2+ transients in 9–13% of either subfornical Organ or Organum vasculosum laminae terminalis astrocytes, respectively, and some glial cells (subfornical Organ: 2%, Organum vasculosum laminae terminalis: 5%) responded to both endothelin analogues. The antagonistic action of BQ123 specific for ET A receptors (74% of all astrocytes tested), and the pronounced responsiveness to the ET B receptor agonist [4Ala]ET-1 (subfornical Organ: 27%, Organum vasculosum laminae terminalis: 35%) demonstrated glial expression of both endothelin receptor subtypes. Agonist-induced elevations in the intracellular calcium concentration proved to be independent of extracellular Ca 2+ . In summary, the results indicate that endothelin(s) interact(s) with Circumventricular Organ astrocytes. Competitive receptor binding techniques using brain tissue sections as well as a fura-2 loaded primary cell culture system of the subfornical Organ and Organum vasculosum laminae terminalis demonstrate glial expression of functional ET A and ET B receptors, with calcium as intracellular messenger emerging primarily from intracellular stores. Endothelin(s) of both circulating and Circumventricular Organ-intrinsic origin may afferently transfer information important for cardiovascular homeostasis to Circumventricular Organs serving as “windows to the brain”.
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Angiotensin II-induced calcium signalling in neurons and astrocytes of rat Circumventricular Organs
Neuroscience, 1998Co-Authors: E Gebke, Andreas Müller, Mirek Jurzak, Rüdiger GerstbergerAbstract:Abstract The subfornical Organ and Organum vasculosum laminae terminalis represent neuroglial Circumventricular Organ structures bordering the anterior third cerebral ventricle. Owing to the absence of the blood–brain barrier, the cellular elements of the subfornical Organ and the Organum vasculosum laminae terminalis can be reached by circulating messenger molecules transferring afferent information. As demonstrated for the control of extracellular fluid composition, the circulating hormone angiotensin II acts on these sensory Circumventricular Organs to induce drinking, elevated peripheral resistance and neurohypophyseal hormone release via interaction with membrane-spanning receptor proteins. To characterize the cell-specific distribution of angiotensin II receptors within the Circumventricular Organs, primary cell cultures derived from the subfornical Organ or Organum vasculosum laminae terminalis of five- to six-day-old rat pups were used to measure alterations in intracellular calcium at the single cell level. Neurons and astrocytes were identified by immunocytochemical staining for specific marker proteins. Bath application of angiotensin II (10 −10 –10 −6 M) dose-dependently induced calcium transients in neurons (19.6%) and astrocytes (15.7%), and angiotensin II threshold concentrations to elicit intracellular calcium signalling proved to be one order of magnitude higher in astrocytes as compared to neurons (10 −9 M). At angiotensin II concentrations higher than 10 −7 M, pronounced desensitization of the angiotensin II receptor occurred. Employing the angiotensin II receptor antagonists losartan (DUP-753; AT 1 -receptor) and PD-123319 (AT 2 -receptor), exclusive expression of the AT 1 receptor subtype coupled to intracellular calcium concentration signalling could be demonstrated for neurons and astrocytes. In all cells examined, the angiotensin II-evoked increase in intracellular calcium concentrations could be fully suppressed in the absence of extracellular calcium. Co-activation by angiotensin II and other agents (vasopressin, its fragment 8-arginine-vasopressin (4–9) , oxytocin, endothelin) was indicated for subfornical Organ neurons and Organum vasculosum laminae terminalis astrocytes.