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Mariko Sugiyama - One of the best experts on this subject based on the ideXlab platform.
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Tanycyte like cells derived from mouse embryonic stem culture show hypothalamic neural stem progenitor cell functions
Endocrinology, 2019Co-Authors: Mayuko Kano, Hidetaka Suga, Takeshi Ishihara, Mayu Sakakibara, Mika Soen, Tomiko Yamada, Hajime Ozaki, Kazuki Mitsumoto, Takatoshi Kasai, Mariko SugiyamaAbstract:Tanycytes have recently been accepted as neural stem/progenitor cells in the postnatal hypothalamus. Persistent retina and anterior neural fold homeobox (Rax) expression is characteristic of Tanycytes in contrast to its transient expression of whole hypothalamic precursors. In this study, we found that Rax+ residual cells in the maturation phase of hypothalamic differentiation in mouse embryonic stem cell (mESC) cultures had similar characteristics to ventral Tanycytes. They expressed typical neural stem/progenitor cell markers, including Sox2, vimentin, and nestin, and differentiated into mature neurons and glial cells. Quantitative RT-PCR analysis showed that Rax+ residual cells expressed Fgf-10, Fgf-18, and Lhx2, which are expressed by ventral Tanycytes. They highly expressed Tanycyte-specific genes Dio2 and Gpr50 compared with Rax+ early hypothalamic progenitor cells. Therefore, Rax+ residual cells in the maturation phase of hypothalamic differentiation were considered to be more differentiated and similar to late progenitor cells and Tanycytes. They self-renewed and formed neurospheres when cultured with exogenous FGF-2. Additionally, these Rax+ neurospheres differentiated into three neuronal lineages (neurons, astrocytes, and oligodendrocytes), including neuropeptide Y+ neuron, that are reported to be differentiated from ventral Tanycytes toward the arcuate nuclei. Thus, Rax+ residual cells were multipotent neural stem/progenitor cells. Rax+ neurospheres were stably passaged and retained high Sox2 expression even after multiple passages. These results suggest the successful induction of Rax+ Tanycyte-like cells from mESCs [induced Tanycyte-like (iTan) cells]. These hypothalamic neural stem/progenitor cells may have potential in regenerative medicine and as a research tool.
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Tanycyte-Like Cells Derived From Mouse Embryonic Stem Culture Show Hypothalamic Neural Stem/Progenitor Cell Functions.
Endocrinology, 2019Co-Authors: Mayuko Kano, Hidetaka Suga, Takeshi Ishihara, Mayu Sakakibara, Mika Soen, Tomiko Yamada, Hajime Ozaki, Kazuki Mitsumoto, Takatoshi Kasai, Mariko SugiyamaAbstract:Tanycytes have recently been accepted as neural stem/progenitor cells in the postnatal hypothalamus. Persistent retina and anterior neural fold homeobox (Rax) expression is characteristic of Tanycytes in contrast to its transient expression of whole hypothalamic precursors. In this study, we found that Rax+ residual cells in the maturation phase of hypothalamic differentiation in mouse embryonic stem cell (mESC) cultures had similar characteristics to ventral Tanycytes. They expressed typical neural stem/progenitor cell markers, including Sox2, vimentin, and nestin, and differentiated into mature neurons and glial cells. Quantitative RT-PCR analysis showed that Rax+ residual cells expressed Fgf-10, Fgf-18, and Lhx2, which are expressed by ventral Tanycytes. They highly expressed Tanycyte-specific genes Dio2 and Gpr50 compared with Rax+ early hypothalamic progenitor cells. Therefore, Rax+ residual cells in the maturation phase of hypothalamic differentiation were considered to be more differentiated and similar to late progenitor cells and Tanycytes. They self-renewed and formed neurospheres when cultured with exogenous FGF-2. Additionally, these Rax+ neurospheres differentiated into three neuronal lineages (neurons, astrocytes, and oligodendrocytes), including neuropeptide Y+ neuron, that are reported to be differentiated from ventral Tanycytes toward the arcuate nuclei. Thus, Rax+ residual cells were multipotent neural stem/progenitor cells. Rax+ neurospheres were stably passaged and retained high Sox2 expression even after multiple passages. These results suggest the successful induction of Rax+ Tanycyte-like cells from mESCs [induced Tanycyte-like (iTan) cells]. These hypothalamic neural stem/progenitor cells may have potential in regenerative medicine and as a research tool.
Francis J P Ebling - One of the best experts on this subject based on the ideXlab platform.
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Tanycytes: Gateway to the hungry brain: An Editorial for "The FGF2-induced Tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway" on https://doi.org/10.1111/jnc.15188.
Journal of neurochemistry, 2020Co-Authors: Francis J P EblingAbstract:Tanycytes are glial cells in the hypothalamus that are functionally part of the blood-brain barrier. They can sense nutrients and metabolites in the circulation such as glucose, then signal to neuronal systems to influence ingestive behaviour and energy storage, and ultimately affect body weight. The complex structure of Tanycytes underpins this function, and communication is dependent upon connexin-43 gap junctions between Tanycytes. This Editorial highlights studies by Recabal and coworkers (Recabal et al., 2020) in the current issue that shed some light on how this happens, and on how FGF2 might induce plasticity in hypothalamic structure through changes in Tanycyte function that are dependent on connexin-43 hemichannels.
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Tanycytes and hypothalamic control of energy metabolism.
Glia, 2018Co-Authors: Francis J P Ebling, Jo E. LewisAbstract:Studies from a number of areas of neuroendocrinology indicate that hypothalamic Tanycytes play a key role in control of energy metabolism. First, profound annual changes in gene expression have been identified in these unusual glial cells in seasonal mammals, for example in genes relating to the transport and metabolism of thyroid hormone into the hypothalamus. The consequent changes in local thyroid hormone availability in the hypothalamus have been shown experimentally to regulate annual cycles in energy intake, storage and expenditure in seasonal species. This is reflected in overt seasonal changes in appetite, body fat composition and torpor. Second, studies in laboratory rodents demonstrate that hypothalamic Tanycytes possess transport mechanisms and receptors that indicate they have a cellular function as nutrient sensors. Ex vivo studies with organotypic Tanycyte cultures confirm that acute changes in nutrient availability alter calcium and purinergic signalling within and between Tanycytes. Finally, Tanycytes are components of a stem cell niche in the hypothalamus whose activity can be regulated by the nutritional environment. Experimental depletion of cell division in the hypothalamus alters the homeostatic response to nutrient excess in mice raised in high fat diets. These convergent lines of evidence suggest that Tanycytes are nutrient and metabolite sensors that impact upon plasticity and neuronal function in the surrounding hypothalamus, and consequently have an important role in energy intake and expenditure.
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Tanycytes As Regulators of Seasonal Cycles in Neuroendocrine Function.
Frontiers in neurology, 2017Co-Authors: Jo E. Lewis, Francis J P EblingAbstract:Annual cycles of physiology and behaviour are highly prevalent in organisms inhabiting temperate and polar regions. Examples in mammals include changes in appetite and body fat composition, hibernation and torpor, growth of antlers, pelage and horns, and seasonal reproduction. The timing of these seasonal cycles reflects an interaction of changing environmental signals, such as daylength, and intrinsic rhythmic processes: circannual clocks. As neuroendocrine signals underlie these rhythmic processes, the focus of most mechanistic studies has been on neuronal systems in the hypothalamus. Recent studies also implicate the pituitary stalk (pars tuberalis) and hypothalamic Tanycytes as key pathways in seasonal timing. The pars tuberalis expresses a high density of melatonin receptors, so is highly responsive to changes in the nocturnal secretion of melatonin from the pineal gland as photoperiod changes across the year. The pars tuberalis in turn regulates Tanycyte function in the adjacent hypothalamus via paracrine signals. Tanycytes are radial glial cells that persist into adulthood and function as a stem cell niche. Their cell soma are embedded in the ependymal lining of the third ventricle, but they also send elaborate projections through the arcuate nucleus, many of which terminate on capillaries in the median eminence. This anatomy underlies their function as sensors of nutrients in the circulation, and as regulators of transport of hormones and metabolites into the hypothalamus. In situ hybridization studies reveal robust seasonal changes in gene expression Tanycytes, for example those controlling transport and metabolism of thyroid hormone and retinoic acid. These hormonal signals play a key role in the initial development of the brain, and experimental manipulation of thyroid hormone availability in the adult hypothalamus can accelerate or block seasonal cyclicity in sheep and Siberian hamsters. We hypothesize that seasonal rhythms depends upon re-use of developmental mechanisms in the adult hypothalamus, and that Tanycytes are key orchestrators of these processes.
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Dual signal transduction pathways activated by TSH receptors in rat primary Tanycyte cultures
Journal of molecular endocrinology, 2015Co-Authors: Matei Bolborea, Francis J P Ebling, Gisela Helfer, Perry BarrettAbstract:Tanycytes play multiple roles in hypothalamic functions, including sensing peripheral nutrients and metabolic hormones, regulating neurosecretion and mediating seasonal cycles of reproduction and metabolic physiology. This last function reflects the expression of TSH receptors in Tanycytes, which detect photoperiod-regulated changes in TSH secretion from the neighbouring pars tuberalis. The present overall aim was to determine the signal transduction pathway by which TSH signals in Tanycytes. Expression of the TSH receptor in Tanycytes of 10-day-old Sprague Dawley rats was observed by in situ hybridisation. Primary ependymal cell cultures prepared from 10-day-old rats were found by immunohistochemistry to express vimentin but not GFAP and by PCR to express mRNA for Dio2, Gpr50, Darpp-32 and Tsh receptors that are characteristic of Tanycytes. Treatment of primary Tanycyte/ependymal cultures with TSH (100 IU/l) increased cAMP as assessed by ELISA and induced a cAMP-independent increase in the phosphorylation of ERK1/2 as assessed by western blot analysis. Furthermore, TSH (100 IU/l) stimulated a 2.17-fold increase in Dio2 mRNA expression. We conclude that TSH signal transduction in cultured Tanycytes signals via Gαs to increase cAMP and via an alternative G protein to increase phosphorylation of ERK1/2.
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photoperiodic regulation of glycogen metabolism glycolysis and glutamine synthesis in Tanycytes of the siberian hamster suggests novel roles of Tanycytes in hypothalamic function
Glia, 2011Co-Authors: Annika Herwig, Matei Bolborea, Gill Campbell, Claus Mayer, Kanishka N Nilaweera, Francis J P Ebling, Peter J. Morgan, Perry BarrettAbstract:The objective of this study is to investigate the impact of photoperiod on the temporal and spatial expression of genes involved in glucose metabolism in the brain of the seasonal mammal Phodopus sungorus (Siberian hamster). In situ hybridization was performed on brain sections obtained from male hamsters held in long photoperiod (high body weight and developed testes) or short photoperiod (reduced body weight with testicular regression). This analysis revealed upregulation in expression of genes involved in glycogen and glucose metabolism in short photoperiod and localized to the Tanycyte layer of the third ventricle. On the basis of these data and a previously identified photoperiod-dependent increase in activity of neighboring hypothalamic neurons, we hypothesized that the observed expression changes may reflect alteration in either metabolic fuel or precursor neurotransmitter supply to surrounding neurons. Gene expression analysis was performed for genes involved in lactate and glutamate transport. This analysis showed that the gene for the lactate transporter MCT2 and glutamate transporter GLAST was decreased in the Tanycyte layer in short photoperiod. Expression of mRNA for glutamine synthetase, the final enzyme in the synthesis of the neuronal neurotransmitter precursor, glutamine, was also decreased in short photoperiod. These data suggest a role for Tanycytes in modulating glutamate concentrations and neurotransmitter supply in the hypothalamic environment.
Antonia Recabal - One of the best experts on this subject based on the ideXlab platform.
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The FGF2-induced Tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway.
Journal of neurochemistry, 2020Co-Authors: Antonia Recabal, Paola Fernández, Sergio López, María José Barahona, Patricio Ordenes, Palma Alejandra, Roberto Elizondo-vega, Carlos Farkas, Amparo Uribe, Teresa CaprileAbstract:In the adult hypothalamus, the neuronal precursor role is attributed to the radial-glia-like cells that line the third-ventricle (3V) wall called Tanycytes. Under nutritional cues, including hypercaloric diets, Tanycytes proliferate and differentiate into mature neurons that moderate body-weight, suggesting that hypothalamic neurogenesis is an adaptive mechanism in response to metabolic changes. Previous studies have shown that the Tanycyte glucose-sensing mechanism depends on connexin-43 hemichannels (Cx43 HCs), purine release, and increased intracellular free calcium ion concentration [(Ca2+ )i ] mediated by purinergic P2Y receptors. Since, Fibroblast Growth Factor 2 (FGF2) causes similar purinergic events in other cell types, we hypothesize that this pathway can be also activated by FGF2 in Tanycytes to promote their proliferation. Here, we used bromodeoxyuridine (BrdU) incorporation to evaluate if FGF2-induced Tanycyte cell division is sensitive to Cx43 HC inhibition in vitro and in vivo. Immunocytochemical analyses showed that cultured Tanycytes maintain the expression of in situ markers. After FGF2 exposure, tanycytic Cx43 HCs opened, enabling release of ATP to the extracellular milieu. Moreover, application of external ATP was enough to induce their cell division, which could be suppressed by Cx43 HC or P2Y1-receptor inhibitors. Similarly, in vivo experiments performed on rats by continuous infusion of FGF2 and a Cx43 HC inhibitor into the 3V, demonstrated that FGF2-induced β-Tanycyte proliferation is sensitive to Cx43 HC blockade. Thus, FGF2 induced Cx43 HC opening, triggered purinergic signaling, and increased β-Tanycytes proliferation, highlighting some of the molecular mechanisms involved in the cell division response of Tanycyte.
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the fgf2 induced Tanycyte proliferation involves a connexin 43 hemichannel purinergic dependent pathway
Journal of Neurochemistry, 2020Co-Authors: Antonia Recabal, Paola Fernández, Sergio López, María José Barahona, Patricio Ordenes, Palma Alejandra, Carlos Farkas, Roberto Elizondovega, Amparo UribeAbstract:In the adult hypothalamus, the neuronal precursor role is attributed to the radial-glia-like cells that line the third-ventricle (3V) wall called Tanycytes. Under nutritional cues, including hypercaloric diets, Tanycytes proliferate and differentiate into mature neurons that moderate body-weight, suggesting that hypothalamic neurogenesis is an adaptive mechanism in response to metabolic changes. Previous studies have shown that the Tanycyte glucose-sensing mechanism depends on connexin-43 hemichannels (Cx43 HCs), purine release, and increased intracellular free calcium ion concentration [(Ca2+ )i ] mediated by purinergic P2Y receptors. Since, Fibroblast Growth Factor 2 (FGF2) causes similar purinergic events in other cell types, we hypothesize that this pathway can be also activated by FGF2 in Tanycytes to promote their proliferation. Here, we used bromodeoxyuridine (BrdU) incorporation to evaluate if FGF2-induced Tanycyte cell division is sensitive to Cx43 HC inhibition in vitro and in vivo. Immunocytochemical analyses showed that cultured Tanycytes maintain the expression of in situ markers. After FGF2 exposure, tanycytic Cx43 HCs opened, enabling release of ATP to the extracellular milieu. Moreover, application of external ATP was enough to induce their cell division, which could be suppressed by Cx43 HC or P2Y1-receptor inhibitors. Similarly, in vivo experiments performed on rats by continuous infusion of FGF2 and a Cx43 HC inhibitor into the 3V, demonstrated that FGF2-induced β-Tanycyte proliferation is sensitive to Cx43 HC blockade. Thus, FGF2 induced Cx43 HC opening, triggered purinergic signaling, and increased β-Tanycytes proliferation, highlighting some of the molecular mechanisms involved in the cell division response of Tanycyte.
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Nutrient Sensing by Hypothalamic Tanycytes.
Frontiers in endocrinology, 2019Co-Authors: Roberto Elizondo-vega, Antonia Recabal, Karina OyarceAbstract:Nutritional signals have long been implicated in the control of cellular processes that take place in the hypothalamus. This includes food intake regulation and energy balance, inflammation, and most recently, neurogenesis. One of the main glial cells residing in the hypothalamus are Tanycytes, radial glial-like cells, whose bodies are located in the lining of the third ventricle, with processes extending to the parenchyma and reaching neuronal nuclei. Their unique anatomical location makes them directly exposed to nutrients in the cerebrospinal fluid. Several research groups have shown that Tanycytes can respond to nutritional signals by different mechanisms, such as calcium signaling, metabolic shift, and changes in proliferation/differentiation potential. Despite cumulative evidence showing Tanycytes have the molecular components to participate in nutrient detection and response, there are no enough functional studies connecting Tanycyte nutrient sensing with hypothalamic functions, nor that highlight the relevance of this process in physiological and pathological context. This review will summarize recent evidence that supports a nutrient sensor role for Tanycytes in the hypothalamus, highlighting the need for more detailed analysis on the actual implications of Tanycyte-nutrient sensing and how this process can be modulated, which might allow the discovery of new metabolic and signaling pathways as therapeutic targets, for the treatment of hypothalamic related diseases.
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Connexin-43 Gap Junctions Are Responsible for the Hypothalamic Tanycyte-Coupled Network.
Frontiers in cellular neuroscience, 2018Co-Authors: Antonia Recabal, Sergio López, Roberto Elizondo-vega, Magdiel Salgado, Estefanía Tarifeño-saldivia, Camille Philippot, Alejandra Palma, Aline Timmermann, Gerald Seifert, Teresa CaprileAbstract:Tanycytes are hypothalamic radial glia-like cells that form the basal wall of the third ventricle (3V) where they sense glucose and modulate neighboring neuronal activity to control feeding behavior. This role requires the coupling of hypothalamic cells since transient decreased hypothalamic Cx43 expression inhibits the increase of brain glucose-induced insulin secretion. Tanycytes have been postulated as possible hypothalamic neuronal precursors due to their privileged position in the hypothalamus that allows them to detect mitogenic signals and because they share the markers and characteristics of neuronal precursors located in other neurogenic niches, including the formation of coupled networks through connexins. Using wild-type (WT), Cx30-/- and Cx30-/-, Cx43fl/fl:glial fibrillary acidic protein (GFAP)-Cre (double knockout, dKO) mouse lines, we demonstrated that Tanycytes are highly coupled to each other and also give rise to a panglial network specifically through Cx43. Using the human GFAP (hGFAP)-enhanced green fluorescent protein (EGFP) transgenic mouse line, we provided evidence that the main parenchymal-coupled cells were astrocytes. In addition, electrophysiological parameters, such as membrane resistance, were altered when Cx43 was genetically absent or pharmacologically inhibited. Finally, in the dKO mouse line, we detected a significant decrease in the number of hypothalamic proliferative parenchymal cells. Our results demonstrate the importance of Cx43 in Tanycyte homotypic and panglial coupling and show that Cx43 function influences the proliferative potential of hypothalamic cells.
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Image_1_Connexin-43 Gap Junctions Are Responsible for the Hypothalamic Tanycyte-Coupled Network.TIF
2018Co-Authors: Antonia Recabal, Sergio López, Roberto Elizondo-vega, Magdiel Salgado, Estefanía Tarifeño-saldivia, Camille Philippot, Alejandra Palma, Aline Timmermann, Gerald Seifert, Teresa CaprileAbstract:Tanycytes are hypothalamic radial glia-like cells that form the basal wall of the third ventricle (3V) where they sense glucose and modulate neighboring neuronal activity to control feeding behavior. This role requires the coupling of hypothalamic cells since transient decreased hypothalamic Cx43 expression inhibits the increase of brain glucose-induced insulin secretion. Tanycytes have been postulated as possible hypothalamic neuronal precursors due to their privileged position in the hypothalamus that allows them to detect mitogenic signals and because they share the markers and characteristics of neuronal precursors located in other neurogenic niches, including the formation of coupled networks through connexins. Using wild-type (WT), Cx30−/– and Cx30−/–, Cx43fl/fl:glial fibrillary acidic protein (GFAP)-Cre (double knockout, dKO) mouse lines, we demonstrated that Tanycytes are highly coupled to each other and also give rise to a panglial network specifically through Cx43. Using the human GFAP (hGFAP)-enhanced green fluorescent protein (EGFP) transgenic mouse line, we provided evidence that the main parenchymal-coupled cells were astrocytes. In addition, electrophysiological parameters, such as membrane resistance, were altered when Cx43 was genetically absent or pharmacologically inhibited. Finally, in the dKO mouse line, we detected a significant decrease in the number of hypothalamic proliferative parenchymal cells. Our results demonstrate the importance of Cx43 in Tanycyte homotypic and panglial coupling and show that Cx43 function influences the proliferative potential of hypothalamic cells.
Vincent Prevot - One of the best experts on this subject based on the ideXlab platform.
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Tanycyte like cells form a blood cerebrospinal fluid barrier in the circumventricular organs of the mouse brain
The Journal of Comparative Neurology, 2013Co-Authors: Fanny Langlet, Vincent Prevot, Amandine Mullier, Sebastien G. Bouret, Bénédicte DehouckAbstract:Tanycytes are highly specialized ependymal cells that form a blood–cerebrospinal fluid (CSF) barrier at the level of the median eminence (ME), a circumventricular organ (CVO) located in the tuberal region of the hypothalamus. This ependymal layer harbors well-organized tight junctions, a hallmark of central nervous system barriers that is lacking in the fenestrated portal vessels of the ME. The displacement of barrier properties from the vascular to the ventricular side allows the diffusion of blood-borne molecules into the parenchyma of the ME while Tanycyte tight junctions control their diffusion into the CSF, thus maintaining brain homeostasis. In the present work, we combined immunohistochemical and permeability studies to investigate the presence of Tanycyte barriers along the ventricular walls of other brain CVOs. Our data indicate that, unlike cuboidal ependymal cells, ependymal cells bordering the CVOs possess long processes that project into the parenchyma of the CVOs to reach the fenestrated capillary network. Remarkably, these Tanycyte-like cells display well-organized tight junctions around their cell bodies. Consistent with these observations, permeability studies show that this ependymal layer acts as a diffusion barrier. Together, our results suggest that Tanycytes are a characteristic feature of all CVOs and yield potential new insights into their involvement in regulating the exchange between the blood, the brain, and the CSF within these “brain windows.”
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Tanycyte-Like Cells Form a Blood–Cerebrospinal Fluid Barrier in the Circumventricular Organs of the Mouse Brain
The Journal of comparative neurology, 2013Co-Authors: Fanny Langlet, Vincent Prevot, Amandine Mullier, Sebastien G. Bouret, Bénédicte DehouckAbstract:Tanycytes are highly specialized ependymal cells that form a blood–cerebrospinal fluid (CSF) barrier at the level of the median eminence (ME), a circumventricular organ (CVO) located in the tuberal region of the hypothalamus. This ependymal layer harbors well-organized tight junctions, a hallmark of central nervous system barriers that is lacking in the fenestrated portal vessels of the ME. The displacement of barrier properties from the vascular to the ventricular side allows the diffusion of blood-borne molecules into the parenchyma of the ME while Tanycyte tight junctions control their diffusion into the CSF, thus maintaining brain homeostasis. In the present work, we combined immunohistochemical and permeability studies to investigate the presence of Tanycyte barriers along the ventricular walls of other brain CVOs. Our data indicate that, unlike cuboidal ependymal cells, ependymal cells bordering the CVOs possess long processes that project into the parenchyma of the CVOs to reach the fenestrated capillary network. Remarkably, these Tanycyte-like cells display well-organized tight junctions around their cell bodies. Consistent with these observations, permeability studies show that this ependymal layer acts as a diffusion barrier. Together, our results suggest that Tanycytes are a characteristic feature of all CVOs and yield potential new insights into their involvement in regulating the exchange between the blood, the brain, and the CSF within these “brain windows.”
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Activation of erbB-1 Signaling in Tanycytes of the Median Eminence Stimulates Transforming Growth Factor � 1 Release via Prostaglandin E 2 Production and Induces Cell Plasticity
2013Co-Authors: Vincent Prevot, Anda Cornea, Alison E Mungenast, Gregory Smiley, Sergio R. OjedaAbstract:The activation of transforming growth factor � (TGF�) – erbB-1 and neuregulin – erbB-4 signaling pathways in hypothalamic astrocytes has been shown to play a key role in the process by which the neuroendocrine brain controls luteinizing hormone-releasing hormone (LHRH) secretion. Earlier studies suggested that Tanycytes, an ependymoglial cell type of the median eminence, regulate LHRH release during the estrous cycle by undergoing plastic changes that alternatively allow or prevent direct access of the LHRH nerve terminals to the portal vasculature. Neither the molecules responsible for these plastic changes nor the underlying controlling mechanisms have been identified. Here we show that cultured Tanycytes express erbB-1 and erbB-2, two of the four members of the erbB receptor family, and respond to TGF � with receptor phosphorylation, release of prostaglandin E2 (PGE2), and a PGE2-dependent increase in the release of TGF�1, a growth factor previously implicated in the glial control of LHRH secretion. Blockade of either erbB-1 receptor signal transduction or prostaglandin synthesis prevented the stimulatory effect of TGF � on both PGE2 and TGF�1 release. Time-lapse studies revealed that TGF � and TGF�1 have dramatically opposite effects on Tanycyte plasticity. Whereas TGF � promotes tanycytic outgrowth, TGF�1 elicits retraction of tanycytic processes. Blockade of metalloproteinase activity abolished the effect of TGF�1, suggesting that TGF�1 induces tanycytic retraction by facilitating dissolution of the extracellular matrix. Prolonged (�12 hr) exposure of Tanycytes to TGF� resulted in focal tanycytic retraction, an effect that was abolished by immunoneutralization of TGF�1 action, indicating that the retraction was attributable to TGF�-induced TGF�1 formation. These in vitro results identify Tanycytes as targets of TGF � action and demonstrat
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Gliotransmission byprostaglandin E2: a prerequisite for GnRH neurona lfunction?
Frontiers in Endocrinology, 2011Co-Authors: Jerome Clasadonte, Ariane Sharif, Marc Baroncini, Vincent PrevotAbstract:Over the past four decades it has become clear that prostaglandin E2 (PGE2), a phospholipid-derived signaling molecule, plays a fundamental role in modulating the gonadotropin-releasing hormone (GnRH) neuroendocrine system and in shaping the hypothalamus. In this review, after a brief historical overview, we highlight studies revealing that PGE2 released by glial cells such as astrocytes and Tanycytes is intimately involved in the active control of GnRH neuronal activity and neurosecretion. Recent evidence suggests that hypothalamic astrocytes surrounding GnRH neuronal cell bodies may respond to neuronal activity with an activation of the erbB receptor tyrosine kinase signaling, triggering the release of PGE2 as a chemical transmitter from the glia themselves, and, in turn, leading to the feedback regulation of GnRH neuronal activity. At the GnRH neurohemal junction, in the median eminence of the hypothalamus, PGE2 is released by Tanycytes in response to cell-cell signaling initiated by glial cells and vascular endothelial cells. Upon its release, PGE2 causes the retraction of the Tanycyte end-feet enwrapping the GnRH nerve terminals, enabling them to approach the adjacent pericapillary space and thus likely facilitating neurohormone diffusion from these nerve terminals into the pituitary portal blood. In view of these new insights, we suggest that synaptically associated astrocytes and perijunctional Tanycytes are integral modulatory elements of GnRH neuronal function at the cell soma/dendrite and nerve terminal levels, respectively.
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Role of estradiol in the dynamic control of Tanycyte plasticity mediated by vascular endothelial cells in the median eminence.
Endocrinology, 2010Co-Authors: Sandrine De Seranno, Xavier D'anglemont De Tassigny, Cecilia Estrella, Anne Loyens, Sergey Kasparov, Danièle Leroy, Sergio R. Ojeda, J.c. Beauvillain, Vincent PrevotAbstract:In the ever-changing physiological context of the neuroendocrine brain, the mechanisms by which cellular events involving neurons, astroglia, and vascular cells are coordinated to bring forth the appropriate neuronal signaling is not yet known but is amenable to examination. In the median eminence of the hypothalamus, endothelial cells are key players in the plasticity of Tanycytes (specialized astroglia) and neuroendocrine synapse efficacy. Here we report that estradiol acts on both purified endothelial cells and isolated Tanycytes to trigger endothelial-to-glial communication that leads to a sudden and massive retraction of Tanycyte processes. The blockade of endothelial nitric oxide synthase by in vitro adenoviral-mediated gene transfer of a dominant-negative form of endothelial nitric oxide synthase abrogates the estradiol-induced Tanycyte plasticity mediated by endothelial cells. In parallel, increases in prostaglandin-E(2) (PGE(2)) due to changes in cyclooxygenase (COX)-1 and COX-2 expression induced by the exposure of Tanycytes to estradiol promote acute Tanycyte plasticity. We also demonstrate by electron microscopy that the administration of PGE(2) to median eminence explants induces rapid neuroglial plasticity at the neurovascular junction of neurons that release GnRH (the neuropeptide controlling reproduction). Conversely, preventing local PGE(2) synthesis in the median eminence of adult female rats with the COX inhibitor indomethacin impairs the ovarian cycle, a process that requires a pulsatile, coordinated delivery of GnRH into the hypothalamo-hypophyseal portal system. Taken together, our findings show that estradiol controls the dialog between endothelial cells and astroglia to regulate neuroglial plasticity in the neuroendocrine brain.
Perry Barrett - One of the best experts on this subject based on the ideXlab platform.
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Dual signal transduction pathways activated by TSH receptors in rat primary Tanycyte cultures
Journal of molecular endocrinology, 2015Co-Authors: Matei Bolborea, Francis J P Ebling, Gisela Helfer, Perry BarrettAbstract:Tanycytes play multiple roles in hypothalamic functions, including sensing peripheral nutrients and metabolic hormones, regulating neurosecretion and mediating seasonal cycles of reproduction and metabolic physiology. This last function reflects the expression of TSH receptors in Tanycytes, which detect photoperiod-regulated changes in TSH secretion from the neighbouring pars tuberalis. The present overall aim was to determine the signal transduction pathway by which TSH signals in Tanycytes. Expression of the TSH receptor in Tanycytes of 10-day-old Sprague Dawley rats was observed by in situ hybridisation. Primary ependymal cell cultures prepared from 10-day-old rats were found by immunohistochemistry to express vimentin but not GFAP and by PCR to express mRNA for Dio2, Gpr50, Darpp-32 and Tsh receptors that are characteristic of Tanycytes. Treatment of primary Tanycyte/ependymal cultures with TSH (100 IU/l) increased cAMP as assessed by ELISA and induced a cAMP-independent increase in the phosphorylation of ERK1/2 as assessed by western blot analysis. Furthermore, TSH (100 IU/l) stimulated a 2.17-fold increase in Dio2 mRNA expression. We conclude that TSH signal transduction in cultured Tanycytes signals via Gαs to increase cAMP and via an alternative G protein to increase phosphorylation of ERK1/2.
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NFκB signaling is essential for the lipopolysaccharide-induced increase of type 2 deiodinase in Tanycytes.
Endocrinology, 2014Co-Authors: E M De Vries, Perry Barrett, Joan Kwakkel, Leslie Eggels, Andries Kalsbeek, Ellen A. Fliers, Anita BoelenAbstract:The enzyme type 2 deiodinase (D2) is a major determinant of T₃ production in the central nervous system. It is highly expressed in Tanycytes, a specialized cell type lining the wall of the third ventricle. During acute inflammation, the expression of D2 in Tanycytes is up-regulated by a mechanism that is poorly understood at present, but we hypothesized that cJun N-terminal kinase 1 (JNK1) and v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) (the 65 kD subunit of NFκB) inflammatory signal transduction pathways are involved. In a mouse model for acute inflammation, we studied the effects of lipopolysaccharide (LPS) on mRNA expression of D2, JNK1, and RelA in the periventricular area (PE) and the arcuate nucleus-median eminence of the hypothalamus. We next investigated LPS-induced D2 expression in primary Tanycyte cell cultures. In the PE, the expression of D2 was increased by LPS. In the arcuate nucleus, but not in the PE, we found increased RelA mRNA expression. Likewise, LPS increased D2 and RelA mRNA expression in primary Tanycyte cell cultures, whereas JNK1 mRNA expression did not change. Phosphorylation of RelA and JNK1 was increased in Tanycyte cell cultures 15-60 minutes after LPS stimulation, confirming activation of these pathways. Finally, inhibition of RelA with the chemical inhibitors sulfasalazine and 4-Methyl-N¹-(3-phenylpropyl)benzene-1,2-diamine (JSH-23) in Tanycyte cell cultures prevented the LPS-induced D2 increase. We conclude that NFκB signaling is essential for the up-regulation of D2 in Tanycytes during inflammation.
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photoperiodic regulation of glycogen metabolism glycolysis and glutamine synthesis in Tanycytes of the siberian hamster suggests novel roles of Tanycytes in hypothalamic function
Glia, 2011Co-Authors: Annika Herwig, Matei Bolborea, Gill Campbell, Claus Mayer, Kanishka N Nilaweera, Francis J P Ebling, Peter J. Morgan, Perry BarrettAbstract:The objective of this study is to investigate the impact of photoperiod on the temporal and spatial expression of genes involved in glucose metabolism in the brain of the seasonal mammal Phodopus sungorus (Siberian hamster). In situ hybridization was performed on brain sections obtained from male hamsters held in long photoperiod (high body weight and developed testes) or short photoperiod (reduced body weight with testicular regression). This analysis revealed upregulation in expression of genes involved in glycogen and glucose metabolism in short photoperiod and localized to the Tanycyte layer of the third ventricle. On the basis of these data and a previously identified photoperiod-dependent increase in activity of neighboring hypothalamic neurons, we hypothesized that the observed expression changes may reflect alteration in either metabolic fuel or precursor neurotransmitter supply to surrounding neurons. Gene expression analysis was performed for genes involved in lactate and glutamate transport. This analysis showed that the gene for the lactate transporter MCT2 and glutamate transporter GLAST was decreased in the Tanycyte layer in short photoperiod. Expression of mRNA for glutamine synthetase, the final enzyme in the synthesis of the neuronal neurotransmitter precursor, glutamine, was also decreased in short photoperiod. These data suggest a role for Tanycytes in modulating glutamate concentrations and neurotransmitter supply in the hypothalamic environment.
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photoperiodic regulation of glycogen metabolism glycolysis and glutamine synthesis in Tanycytes of the siberian hamster suggests novel roles of Tanycytes in hypothalamic function
Glia, 2011Co-Authors: Annika Herwig, Matei Bolborea, Gill Campbell, Claus Mayer, Kanishka N Nilaweera, Francis J P Ebling, Peter J. Morgan, Perry BarrettAbstract:The objective of this study is to investigate the impact of photoperiod on the temporal and spatial expression of genes involved in glucose metabolism in the brain of the seasonal mammal Phodopus sungorus (Siberian hamster). In situ hybridization was performed on brain sections obtained from male hamsters held in long photoperiod (high body weight and developed testes) or short photoperiod (reduced body weight with testicular regression). This analysis revealed upregulation in expression of genes involved in glycogen and glucose metabolism in short photoperiod and localized to the Tanycyte layer of the third ventricle. On the basis of these data and a previously identified photoperiod-dependent increase in activity of neighboring hypothalamic neurons, we hypothesized that the observed expression changes may reflect alteration in either metabolic fuel or precursor neurotransmitter supply to surrounding neurons. Gene expression analysis was performed for genes involved in lactate and glutamate transport. This analysis showed that the gene for the lactate transporter MCT2 and glutamate transporter GLAST was decreased in the Tanycyte layer in short photoperiod. Expression of mRNA for glutamine synthetase, the final enzyme in the synthesis of the neuronal neurotransmitter precursor, glutamine, was also decreased in short photoperiod. These data suggest a role for Tanycytes in modulating glutamate concentrations and neurotransmitter supply in the hypothalamic environment.
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photoperiodic regulation of cellular retinoic acid binding protein 1 gpr50 and nestin in Tanycytes of the third ventricle ependymal layer of the siberian hamster
Journal of Endocrinology, 2006Co-Authors: Perry Barrett, Alexander W Ross, Dana Wilson, Scott E Graham, Sandrine Schuhler, Sandrine M Dupre, Julian G Mercer, Francis J P Ebling, Elena A Ivanova, Andrew S. I. LoudonAbstract:Tanycytes in the ependymal layer of the third ventricle act both as a barrier and a communication gateway between the cerebrospinal fluid, brain and portal blood supply to the pituitary gland. However, the range, importance and mechanisms involved in the function of Tanycytes remain to be explored. In this study, we have utilized a photoperiodic animal to examine the expression of three unrelated gene sequences in relation to photoperiod-induced changes in seasonal physiology and behaviour. We demonstrate that cellular retinoic acid-binding protein 1 (CRBP1), a retinoic acid transport protein, GPR50, an orphan G-protein-coupled receptor and nestin, an intermediate filament protein, are down-regulated in short-day photoperiods. The distribution of the three sequences is very similar, with expression located in cells with Tanycyte morphology in the region of the ependymal layer where Tanycytes are located. Furthermore, CRBP1 expression in the ependymal layer is shown to be independent of a circadian clock and altered testosterone levels associated with testicular regression in short photoperiod. Pinealectomy of Siberian hamsters demonstrates CRBP1 expression is likely to be dependent on melatonin output from the pineal gland. This provides evidence that Tanycytes are seasonally responsive cells and are likely to be an important part of the mechanism to facilitate seasonal physiology and behaviour in the Siberian hamster.
