Hypothalamic Tanycytes Research Articles

Dynamic localization of glucokinase and its regulatory protein in hypothalamic tanycytes.

Glucokinase (GK), the hexokinase involved in glucose sensing in pancreatic β cells, is also expressed in hypothalamic tanycytes, which cover the ventricular walls of the basal hypothalamus and are implicated in an indirect control of neuronal activity by glucose. Previously, we demonstrated that GK was preferentially localized in tanycyte nuclei in euglycemic rats, which has been reported in hepatocytes and is suggestive of the presence of the GK regulatory protein, GKRP. In the present study, GK intracellular localization in hypothalamic and hepatic tissues of the same rats under several glycemic conditions was compared using confocal microscopy and Western blot analysis. In the hypothalamus, increased GK nuclear localization was observed in hyperglycemic conditions; however, it was primarily localized in the cytoplasm in hepatic tissue under the same conditions. Both GK and GKRP were next cloned from primary cultures of tanycytes. Expression of GK by Escherichia coli revealed a functional cooperative protein with a S0.5 of 10 mM. GKRP, expressed in Saccharomyces cerevisiae, inhibited GK activity in vitro with a Ki 0.2 µM. We also demonstrated increased nuclear reactivity of both GK and GKRP in response to high glucose concentrations in tanycyte cultures. These data were confirmed using Western blot analysis of nuclear extracts. Results indicate that GK undergoes short-term regulation by nuclear compartmentalization. Thus, in tanycytes, GK can act as a molecular switch to arrest cellular responses to increased glucose.

Sustained Alterations of Hypothalamic Tanycytes During Posttraumatic Hypopituitarism in Male Mice

Traumatic brain injury is a leading cause of hypopituitarism, which compromises patients' recovery, quality of life, and life span. To date, there are no means other than standardized animal studies to provide insights into the mechanisms of posttraumatic hypopituitarism. We have found that GH levels were impaired after inducing a controlled cortical impact (CCI) in mice. Furthermore, GHRH stimulation enhanced GH to lower level in injured than in control or sham mice. Because many characteristics were unchanged in the pituitary glands of CCI mice, we looked for changes at the hypothalamic level. Hypertrophied astrocytes were seen both within the arcuate nucleus and the median eminence, two pivotal structures of the GH axis, spatially remote to the injury site. In the arcuate nucleus, GHRH neurons were unaltered. In the median eminence, injured mice exhibited unexpected alterations. First, the distributions of claudin-1 and zonula occludens-1 between tanycytes were disorganized, suggesting tight junction disruptions. Second, endogenous IgG was increased in the vicinity of the third ventricle, suggesting abnormal barrier properties after CCI. Third, intracerebroventricular injection of a fluorescent-dextran derivative highly stained the hypothalamic parenchyma only after CCI, demonstrating an increased permeability of the third ventricle edges. This alteration of the third ventricle might jeopardize the communication between the hypothalamus and the pituitary gland. In conclusion, the phenotype of CCI mice had similarities to the posttraumatic hypopituitarism seen in humans with intact pituitary gland and pituitary stalk. It is the first report of a pathological status in which tanycyte dysfunctions appear as a major acquired syndrome.

Hypothalamic Tanycytes: Gatekeepers to Metabolic Control

How circulating signals of hunger and satiety enter the brain to reach neurons that govern energy balance haslong remained a matter of controversy and speculation. Balland etal. (2014) now elucidate molecular mechanisms by which a highly specialized hypothalamic glial cell regulates transport of leptin across the blood-brain barrier.

Hypothalamic Tanycytes Are an ERK-Gated Conduit for Leptin into the Brain

Leptin secreted by adipocytes acts on the brain to reduce food intake by regulating neuronal activity in the mediobasal hypothalamus (MBH). Obesity is associated with resistance to high circulating leptin levels. Here, we demonstrate that peripherally administered leptin activates its receptor (LepR) in median eminence tanycytes followed by MBH neurons, a process requiring tanycytic ERK signaling and the passage of leptin through the cerebrospinal fluid. In mice lacking the signal-transducing LepRb isoform or with diet-induced obesity, leptin taken up by tanycytes accumulates in the median eminence and fails to reach the MBH. Triggering ERK signaling in tanycytes with EGF reestablishes leptin transport, elicits MBH neuron activation and energy expenditure in obese animals, and accelerates the restoration of leptin sensitivity upon the return to a normal-fat diet. ERK-dependent leptin transport by tanycytes could thus play a critical role in the pathophysiology of leptin resistance, and holds therapeutic potential for treating obesity.

Rax regulates hypothalamic tanycyte differentiation and barrier function in mice

The wall of the ventral third ventricle is composed of two distinct cell populations: tanycytes and ependymal cells. Tanycytes regulate many aspects of hypothalamic physiology, but little is known about the transcriptional network that regulates their development and function. We observed that the retina and anterior neural fold homeobox transcription factor (Rax) is selectively expressed in hypothalamic tanycytes, and showed a complementary pattern of expression to markers of hypothalamic ependymal cells, such as Rarres2 (retinoic acid receptor responder [tazarotene induced] 2). To determine whether Rax controls tanycyte differentiation and function, we generated Rax haploinsufficient mice and examined their cellular and molecular phenotype in adulthood. These mice appeared grossly normal, but careful examination revealed a thinning of the third ventricular wall and reduction of both tanycyte and ependymal markers. These experiments show that Rax is required for hypothalamic tanycyte and ependymal cell differentiation. Rax haploinsufficiency also resulted in the ectopic presence of ependymal cells in the α2 tanycytic zone, where few ependymal cells are normally found, suggesting that Rax is selectively required for α2 tanycyte differentiation. These changes in the ventricular wall were associated with reduced diffusion of Evans Blue tracer from the ventricle to the hypothalamic parenchyma, with no apparent repercussion on the gross anatomical or behavioral phenotype of these mice. In conclusion, we have provided evidence that Rax is required for the normal differentiation and patterning of hypothalamic tanycytes and ependymal cells, as well as for maintenance of the cerebrospinal fluid-hypothalamus barrier.

Co-localization of serine/threonine kinase 33 (Stk33) and vimentin in the hypothalamus

We investigate the immunoreactivity of serine/threonine kinase 33 (Stk33) and of vimentin in the brain of mouse, rat and hamster. Using a Stk33-specific polyclonal antibody, we show by immunofluorescence staining that Stk33 is present in a variety of brain regions. We found a strong staining in the ependymal lining of all cerebral ventricles and the central canal of the spinal cord as well as in hypothalamic tanycytes. Stk33 immunoreactivity was also found in circumventricular organs such as the area postrema, subfornical organ and pituitary and pineal glands. Double-immunostaining experiments with antibodies against Stk33 and vimentin showed a striking colocalization of Stk33 and vimentin. As shown previously, Stk33 phosphorylates recombinant vimentin in vitro. Co-immunoprecipitation experiments and co-sedimentation assays indicate that Stk33 and vimentin are associated in vivo and that this association does not depend on further interacting partners (Brauksiepe et al. in BMC Biochem 9:25, 2008). This indicates that Stk33 is involved in the dynamics of vimentin polymerization/depolymerization. Since in tanycytes the vimentin expression is regulated by the photoperiod (Kameda et al. in Cell Tissue Res 314:251-262, 2003), we determine whether this also holds true for Stk33. We study hypothalamic sections from adult Djungarian hamsters (Phodopus sungorus) held under either long photoperiods (L:D 16:8h) or short photoperiods (L:D 8:16h) for 2months. In addition, we examine whether age-dependent changes in Stk33 protein content exist. Our results show that Stk33 in tanycytes is regulated by the photoperiod as is the case for vimentin. Stk33 may participate in photoperiodic regulation of the endocrine system.

A monoclonal antibody targetting the FGFR‐1c isoform reduces body weight and food intake, which is, associated with a suppression of deiodinase 2 mRNA expression in hypothalamic tanycytes

FGF21 plays a role in the peripheral regulation of energy balance, but its putative receptor (FGFR1c) is also expressed in tanycyte cells of the hypothalamus. The objective of the present study was to investigate the possible central actions of a monoclonal antibody (H7) that specifically targets FGFR1c in a natural model of adiposity, the Siberian hamster. Hypothalamic thyroid hormone availability, controlled by tanycytes, is the key regulator of seasonal cycles of body weight, so we aimed to determine the effect of H7 on local regulators of thyroid hormone availability: deiodinase enzymes DIO2 and DIO3. Hamsters maintained in their long day fat state (LD; n=12) or short day lean state (SD; n=12) were treated with H7 (n=6, 3 mg/kg, sc) or vehicle (n=6/photoperiod). This resulted in a significant reduction in food intake over the 72h treatment period in hamsters in LD (~60%), and a smaller reduction in food intake in SD (~40%). In LD, treatment with H7 resulted in a significant decrease (~50%) in DIO2 mRNA expression in the tanycyte layer of the medial basal hypothalamus. In SD, endogenous DIO2 expression was significantly lower than in LD as expected but H7 treatment did not significantly decrease its expression. In summary, a monoclonal antibody specifically targeting the FGFR1c isoform reduces food intake and body weight in a natural model of adiposity. These effects are far more substantial in hamster maintained in their LD fat state and appear to be associated with the reduction in mRNA expression of the deiodinase enzyme, DIO2.Supported by Eli Lilly and a BBSRC studentship.

Feasibility of direct mapping of cerebral fluorodeoxy‐D‐glucose metabolism in situ at subcellular resolution using soft X‐ray fluorescence

Glucose metabolism is difficult to image with cellular resolution in mammalian brain tissue, particularly with (18) fluorodeoxy-D-glucose (FDG) positron emission tomography (PET). To this end, we explored the potential of synchrotron-based low-energy X-ray fluorescence (LEXRF) to image the stable isotope of fluorine (F) in phosphorylated FDG (DG-6P) at 1 μm(2) spatial resolution in 3-μm-thick brain slices. The excitation-dependent fluorescence F signal at 676 eV varied linearly with FDG concentration between 0.5 and 10 mM, whereas the endogenous background F signal was undetectable in brain. To validate LEXRF mapping of fluorine, FDG was administered in vitro and in vivo, and the fluorine LEXRF signal from intracellular trapped FDG-6P over selected brain areas rich in radial glia was spectrally quantitated at 1 μm(2) resolution. The subsequent generation of spatial LEXRF maps of F reproduced the expected localization and gradients of glucose metabolism in retinal Müller glia. In addition, FDG uptake was localized to periventricular hypothalamic tanycytes, whose morphological features were imaged simultaneously by X-ray absorption. We conclude that the high specificity of photon emission from F and its spatial mapping at ≤1 μm resolution demonstrates the ability to identify glucose uptake at subcellular resolution and holds remarkable potential for imaging glucose metabolism in biological tissue.

Doublecortin and doublecortin‐like are expressed in overlapping and non‐overlapping neuronal cell population: Implications for neurogenesis

We have characterized the expression of doublecortin-like (DCL), a microtubule-associated protein involved in embryonic neurogenesis that is highly homologous to doublecortin (DCX), in the adult mouse brain. To this end, we developed a DCL-specific antibody and used this to compare DCL expression with DCX. In the neurogenic regions of the adult brain like the subventricular zone (SVZ), the rostral migratory stream (RMS), the olfactory bulb (OB), and the hippocampus, DCL colocalizes with DCX in immature neuronal cell populations. In contrast to DCX, we also found high DCL expression in three other brain regions with suspected neurogenesis or neuronal plasticity. First, the radial glia-like, hypothalamic tanycytes show high DCL expression that partly colocalizes with the neural stem cell marker vimentin. Second, DCL expression is found in cells of the suprachiasmatic nucleus (SCN), which lacks expression of the adult neuron marker NeuN. Third, a novel region exhibiting DCL expression is part of the olfactory tubercle where DCL is found in the neuropil of the islands of Calleja (ICj). Our findings define DCL as a novel marker for specific aspects of adult neurogenesis, which partly overlap with DCX. In addition, we propose unique roles for DCL in adult neurogenesis and we suggest high levels of neuronal plasticity in tanycytes, SCN, and ICj.

Doublecortin and doublecortin‐like are expressed in overlapping and non‐overlapping neuronal cell population: Implications for neurogenesis

AbstractWe have characterized the expression of doublecortin‐like (DCL), a microtubule‐associated protein involved in embryonic neurogenesis that is highly homologous to doublecortin (DCX), in the adult mouse brain. To this end, we developed a DCL‐specific antibody and used this to compare DCL expression with DCX. In the neurogenic regions of the adult brain like the subventricular zone (SVZ), the rostral migratory stream (RMS), the olfactory bulb (OB), and the hippocampus, DCL colocalizes with DCX in immature neuronal cell populations. In contrast to DCX, we also found high DCL expression in three other brain regions with suspected neurogenesis or neuronal plasticity. First, the radial glia‐like, hypothalamic tanycytes show high DCL expression that partly colocalizes with the neural stem cell marker vimentin. Second, DCL expression is found in cells of the suprachiasmatic nucleus (SCN), which lacks expression of the adult neuron marker NeuN. Third, a novel region exhibiting DCL expression is part of the olfactory tubercle where DCL is found in the neuropil of the islands of Calleja (ICj). Our findings define DCL as a novel marker for specific aspects of adult neurogenesis, which partly overlap with DCX. In addition, we propose unique roles for DCL in adult neurogenesis and we suggest high levels of neuronal plasticity in tanycytes, SCN, and ICj. J. Comp. Neurol. 520:2805–2823, 2012. © 2012 Wiley Periodicals, Inc.

International Conference on Purinergic Drugs and Targets—4th Joint German–Italian Purine Club Meeting, Bonn, Germany, July 22–25, 2011

International Conference on Purinergic Drugs and Targets—4th Joint German–Italian Purine Club Meeting, Bonn, Germany, July 22–25, 2011

Thyroxine-induced expression of pyroglutamyl peptidase II and inhibition of TSH release precedes suppression of TRH mRNA and requires type 2 deiodinase

Suppression of TSH release from the hypothyroid thyrotrophs is one of the most rapid effects of 3,3',5'-triiodothyronine (T(3)) or thyroxine (T(4)). It is initiated within an hour, precedes the decrease in TSHβ mRNA inhibition and is blocked by inhibitors of mRNA or protein synthesis. TSH elevation in primary hypothyroidism requires both the loss of feedback inhibition by thyroid hormone in the thyrotrophs and the positive effects of TRH. Another event in this feedback regulation may be the thyroid hormone-mediated induction of the TRH-inactivating pyroglutamyl peptidase II (PPII) in the hypothalamic tanycytes. This study compared the chronology of the acute effects of T(3) or T(4) on TSH suppression, TRH mRNA in the hypothalamic paraventricular nucleus (PVN), and the induction of tanycyte PPII. In wild-type mice, T(3) or T(4) caused a 50% decrease in serum TSH in hypothyroid mice by 5 h. There was no change in TRH mRNA in PVN over this interval, but there was a significant increase in PPII mRNA in the tanycytes. In mice with genetic inactivation of the type 2 iodothyronine deiodinase, T(3) decreased serum TSH and increased PPII mRNA levels, while T(4)-treatment was ineffective. We conclude that the rapid suppression of TSH in the hypothyroid mouse by T(3) occurs prior to a decrease in TRH mRNA though TRH inactivation may be occurring in the median eminence through the rapid induction of tanycyte PPII. The effect of T(4), but not T(3), requires the type 2 iodothyronine deiodinase.

ATP‐mediated glucosensing by hypothalamic tanycytes

The brain plays a vital role in the regulation of food intake, appetite and ultimately body weight.Neurons in the hypothalamic arcuate nucleus, the ventromedial hypothalamic nuclei(VMH)and the lateral hypothalamus are sensitive to a number of circulating signals such as leptin, grehlin, insulin and glucose. These neurons are part of a network that integrates this information to regulate feeding and appetite. Hypothalamic tanycytes contact the cerebral spinal fluid of the third ventricle and send processes into the parenchyma. A subset of tanycytes are located close to, and send processes towards, the hypothalamic nuclei that contain neurons that are glucosensitive and are involved in the regulation of feeding. Nevertheless the signalling properties of tanycytes remain largely unstudied. We now demonstrate that tanycytes signal via waves of intracellular Ca2+; they respond strongly to ATP, histamine and acetylcholine – transmitters associated with the drive to feed. Selective stimulation by glucose of tanycyte cell bodies evokes robust ATP-mediated Ca2+ responses. Tanycytes release ATP in response to glucose. Furthermore tanycytes also respond to non-metabolisable analogues of glucose. Although tanycytes have been proposed as glucosensors, our study provides the first direct demonstration of this hypothesis.Tanycytes must therefore now be considered as active signalling cells within the brain that can respond to a number of neuronally derived and circulating transmitters and metabolites.

Developmental expression of type 2 deiodinase in the chicken hypothalamus

Event Abstract Back to Event Developmental expression of type 2 deiodinase in the chicken hypothalamus P. Mohácsik1, T. Füzesi1, E. Hadadi1, E. Szabó1, M. Doleschall1, P. Egri1, Z. Liposits1, C. Fekete1 and B. Gereben1* 1 Hungarian Academy of Sciences, Institute of Experimental Medicine, Hungary Thyroid hormone is an essential factor of brain development and function. Thyroxine is a pro-hormone that needs to be converted to 3,5,3’-triiodothyronine (T3) to be able to bind the thyroid hormone receptors. Type 2 deiodinase (D2) is the key enzyme that generates T3 in the brain. D2 is abundantly expressed in hypothalamic tanycytes that are special glial cells lining the floor and walls of the third ventricles. In chicken, adenohypophysis starts promoting thyroidal secretion at embryonic day (E) 11.5, while thyroid hormones start exerting their negative feedback effect on the TSH production only at E19. It can be hypothesized that a special pattern of D2-mediated T3 generation in developing hypothalamus could be required for the development of T3 dependent negative feedback. Using in situ hybridization, we detected D2 mRNA in tanycytes in the floor and walls of the third ventricle at E13 in the chicken mediobasal hypothalamus. At this stage, the mRNA of the Nkx-2.1 transcription factor could be also detected in tanycytes while it was absent from the perivascular space where D2 expressing astrocytes are present. Promoter studies in U87 glioma cells proved that Nkx-2.1 can induce transcription of the cdio2 gene. In conclusion, the appearance of Nkx-2.1 mediated D2 expression in chicken tanycytes well before the onset of feedback suggests that D2 expression in these cells could be required, but not sufficient to initiate T3 dependent negative feedback in the hypothalamus. Keywords: Neuroendocrinology, Neuroscience Conference: 13th Conference of the Hungarian Neuroscience Society (MITT), Budapest, Hungary, 20 Jan - 22 Jan, 2011. Presentation Type: Abstract Topic: Neuroendocrinology Citation: Mohácsik P, Füzesi T, Hadadi E, Szabó E, Doleschall M, Egri P, Liposits Z, Fekete C and Gereben B (2011). Developmental expression of type 2 deiodinase in the chicken hypothalamus. Front. Neurosci. Conference Abstract: 13th Conference of the Hungarian Neuroscience Society (MITT). doi: 10.3389/conf.fnins.2011.84.00177 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Mar 2011; Published Online: 23 Mar 2011. * Correspondence: Dr. B. Gereben, Hungarian Academy of Sciences, Institute of Experimental Medicine, Budapest, Hungary, gereben@koki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers P. Mohácsik T. Füzesi E. Hadadi E. Szabó M. Doleschall P. Egri Z. Liposits C. Fekete B. Gereben Google P. Mohácsik T. Füzesi E. Hadadi E. Szabó M. Doleschall P. Egri Z. Liposits C. Fekete B. Gereben Google Scholar P. Mohácsik T. Füzesi E. Hadadi E. Szabó M. Doleschall P. Egri Z. Liposits C. Fekete B. Gereben PubMed P. Mohácsik T. Füzesi E. Hadadi E. Szabó M. Doleschall P. Egri Z. Liposits C. Fekete B. Gereben Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Differential distribution of tight junction proteins suggests a role for tanycytes in blood‐hypothalamus barrier regulation in the adult mouse brain

The median eminence is one of the seven so-called circumventricular organs. It is located in the basal hypothalamus, ventral to the third ventricle and adjacent to the arcuate nucleus. This structure characteristically contains a rich capillary plexus and features a fenestrated endothelium, making it a direct target of blood-borne molecules. The median eminence also contains highly specialized ependymal cells called tanycytes, which line the floor of the third ventricle. It has been hypothesized that one of the functions of these cells is to create a barrier that prevents substances in the portal capillary spaces from entering the brain. In this paper, we utilize immunohistochemistry to study the expression of tight junction proteins in the cells that compose the median eminence in adult mice. Our results indicate that tanycytes of the median eminence express occludin, ZO-1, and claudin 1 and 5, but not claudin 3. Remarkably, these molecules are organized as a continuous belt around the cell bodies of the tanycytes that line the ventral part of the third ventricle. In contrast, the tanycytes at the periphery of the arcuate nucleus do not express claudin 1 and instead exhibit a disorganized expression pattern of occludin, ZO-1, and claudin 5. Consistent with these observations, permeability studies using peripheral or central injections of Evans blue dye show that only the tanycytes of the median eminence are joined at their apices by functional tight junctions, whereas tanycytes located at the level of the arcuate nucleus form a permeable layer. In conclusion, this study reveals a unique expression pattern of tight junction proteins in hypothalamic tanycytes, which yields new insights into their barrier properties.

Corrigendum

CorrigendaCorrigendumPublished Online:01 Nov 2009https://doi.org/10.1152/ajpregu.zh6-7009-corr.2009Original articleMoreSectionsPDF (529 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Volume 65, May 2009Herwig A, Wilson D, Logie TJ, Boelen A, Morgan PJ, Mercer JG, Barrett P. Photoperiod and acute energy deficits interact on components of the thyroid hormone system in hypothalamic tanycytes of the Siberian hamster. Am J Physiol Regul Integr Comp Physiol 296: , 2009. First published March 18, 2009; doi:10.1152/ajpregu.90755.2008 (http://ajpregu.physiology.org/cgi/content/full/296/5/R1307).In the original Figure 1A, the lower left panel was mistakenly a copy of the one on the lower right. The corrected figure appears below with its original legend.Fig. 1.Quantification of type II (D2) and III (D3) deiodinase (Dio2 and Dio3) mRNA expression in the 3rd ventricular tanycyte layer of Siberian hamster in long-day (LD) or short-day (SD) photoperiod with or without 48 h of starvation. A and C: representative autoradiographs of coronal brain sections from each of the 4 treatment conditions hybridized with a probe for Dio2 and Dio3. B and D: quantification of autoradiograph signals for Dio2 and Dio3 mRNA expression. Expression was normalized to the highest value obtained for each probe. Solid bars, ad libitum-fed hamsters; gray bars, fold-restricted (48-h-starved) animals. *P < 0.05; ***P < 0.001 by 2-way ANOVA and Tukey's post hoc test for Dio2 and by t-test for Dio3.Download figureDownload PowerPointIn the original Figure 4E, the panel on the upper right was mistakenly a copy of the panel on the upper left side. The corrected figure appears below with its original legend.Fig. 4.Quantification of VGF, neuropeptide Y (NPY), and thyrotropin-releasing hormone (TRH) mRNA expression in the hypothalamus of the Siberian hamster. A: representative autoradiographs of coronal brain sections from each of the treatment conditions hybridized with a probe for VGF. B: quantification of VGF mRNA expression in the dorsal region of the medial posterior area of the arcuate nucleus (dmpARC) of hamsters in the SD photoperiod (no expression in LD) with and without 48 h of starvation. C: autoradiographs of coronal brain sections from each of the treatment conditions hybridized with a probe for NPY. D: quantification of NPY expression in the arcuate nucleus of hamsters held in LD and SD photoperiods with and without 48 h of starvation. E: autoradiographs of coronal brain sections from each of the treatment conditions hybridized with a probe for TRH. F: quantification of TRH mRNA expression in the paraventricular nucleus. Expression was normalized to the highest value for each probe. Solid bars, ad libitum-fed hamsters; gray bars, starved hamsters. *P < 0.05; ***P < 0.001 by 2-way ANOVA and Tukey's post hoc test.Download figureDownload PowerPointThis article has no references to display. Download PDF Previous Back to Top FiguresReferencesRelatedInformationRelated ArticlesPhotoperiod and acute energy deficits interact on components of the thyroid hormone system in hypothalamic tanycytes of the Siberian hamster 01 May 2009American Journal of Physiology-Regulatory, Integrative and Comparative Physiology More from this issue > Volume 297Issue 5November 2009Pages R1624-R1624 Copyright & PermissionsCopyright © 2009 American Physiological Societyhttps://doi.org/10.1152/ajpregu.zh6-7009-corr.2009History Published online 1 November 2009 Published in print 1 November 2009 Metrics

Photoperiod and acute energy deficits interact on components of the thyroid hormone system in hypothalamic tanycytes of the Siberian hamster

In the Siberian hamster, seasonal weight loss occurs gradually over many weeks during autumn and winter. This is driven by a regulatory mechanism that is able to integrate duration of exposure to short days (SDs) with the size of body energy reserves. After food restriction in SDs, followed by ad libitum refeeding, body weight of the hamster does not return to its former level; rather, it increases to a level defined by the length of time spent in SDs. In this report, we show that components of the thyroid hormone system that are involved in seasonal weight loss change expression in response to 48 h of starvation. Eight weeks in an SD photoperiod induced weight loss in the Siberian hamster. In the hypothalamus of these hamsters, type II deiodinase expression was decreased and type III deiodinase expression was induced, but there was no change in hypothalamic neuropeptide Y or thyrotropin-releasing hormone gene expression. For the first time, we show that the thyroid hormone transporter monocarboxylate transporter 8 is expressed in tanycytes and is increased in response to an SD photoperiod. Food restriction (48 h of starvation) reversed the direction of gene expression change for type II and III deiodinase and monocarboxylate transporter 8 induced by SD photoperiods. Furthermore, fasting increased neuropeptide Y expression and decreased thyrotropin-releasing hormone expression. VGF, a gene upregulated in SDs in the dorsal region of the medial posterior area of the arcuate nucleus, was not changed by starvation. These data point to a mechanism whereby energy deprivation can interact with an SD photoperiod on hypothalamic tanycytes to regulate components of the thyroid hormone system involved in photoperiodic regulation of seasonal physiology.

Characterization of the Teb4 ubiquitin ligase of type 2 deiodinase

Event Abstract Back to Event Characterization of the Teb4 ubiquitin ligase of type 2 deiodinase Peter Egri1, Gabor Wittmann1, Csaba Fekete1, 2 and Balázs Gereben1* 1 Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary 2 Tufts-Medical Center, Diabetes, and Metabolism, United States Thyroid hormone, a highly potent differentiation factor plays a crucial role in the development and function of the central nervous system. In order to bind its receptor, the pro-hormone thyroxine (T4) has to be converted to T3 by the type 2 deiodinase selenoenzyme (D2). T3 generation by D2 is down-regulated via the ubiquitin/proteasomal system and Doa10 has recently been suggested as a D2 ubiquitin ligase (E3) in yeast. We studied the distribution of the mammalian Doa10 ortholog, TEB4 in rat tissues and in D2 expressing cells of the brain, namely tanycytes and astrocytes. TEB4 mRNA was detected both in D2 expressing and in non-expressing tissues including the brain, pituitary, liver, kidney, skeletal muscle, heart and brown adipose tissue, but not in the thyroid. This distribution was similar to that of the other D2 ubiquitin ligase WSB1. In the brain, in situ hybridization detected TEB4 expression in tanycytes in the wall of the third ventricle in the mediobasal hypothalamus. TEB4 expression in astrocytes was region-specific; GFAP positive astrocytes expressed TEB4 in the cerebellum, but not in other brain regions. However, strong TEB4 hybridization signal was observed in GFAP-negative cells in different brain regions. Our data demonstrated that similarly to WSB1, the morphological basis for TEB4 mediated regulation of T3 generation is present in hypothalamic tanycytes. However, D2 ubiquitination in astrocytes by TEB4 and WSB1 seems region-specific in the brain. In addition, the expression of TEB4 in non-D2 expressing cells suggests that D2 is not the only substrate of this E3 protein. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Homeostatic regulatory mechanisms Citation: Egri P, Wittmann G, Fekete C and Gereben B (2009). Characterization of the Teb4 ubiquitin ligase of type 2 deiodinase. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.009 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Feb 2009; Published Online: 25 Feb 2009. * Correspondence: Balázs Gereben, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary, gereben@koki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Peter Egri Gabor Wittmann Csaba Fekete Balázs Gereben Google Peter Egri Gabor Wittmann Csaba Fekete Balázs Gereben Google Scholar Peter Egri Gabor Wittmann Csaba Fekete Balázs Gereben PubMed Peter Egri Gabor Wittmann Csaba Fekete Balázs Gereben Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Localization of phospho-tyrosine489-β-adducin immunoreactivity in the hypothalamic tanycytes and its involvement in energy homeostasis

β-Adducin is a cytoskeletal protein that interacts with the actin filaments to suppress actin polymerization and facilitate actin-spectrin binding. We have previously shown that β-adducin is phosphorylated by Fyn at tyrosine489 in the rat brain and bound to its Src-homology 2 domain. In the present study, we examined the immunohistochemical localization of the tyrosine489-phosphorylated form of β-adducin (pY489-β-adducin) in the rat brain. Among brain regions, highest immunoreactivity was located in the hypothalamic tanycytes that are of glial origin lining around the third cerebral ventricle. Their immunoreactive processes extended into the arcuate nucleus, ventromedial hypothalamus and the median eminence. In addition, the pY489-β-adducin immunoreactivity in the tanycytes was enhanced after fasting for 36–48 h, being associated with a morphological change of the DARPP-32-immunoreactivity. Intraperitoneal injection of 2-deoxy- d-glucose also enhances pY489-β-adducin immunoreactivity in the tanycytes, along with increased food intake. These results suggest that tyrosine phosphorylation of β-adducin in the tanycytes is involved in hypothalamic regulation of food intake and energy homeostasis.

Ependymal Cell Differentiation and GLUT1 Expression is a Synchronous Process in the Ventricular Wall

Ependymal cells appear to be totally differentiated during the first 3 weeks in the mouse brain. Early during postnatal development ependymal cells differentiate and undergo metabolic activation, which is accompanied by increased glucose uptake. We propose that ependymal cells induce an overexpression of the glucose transporter, GLUT1, during the first 2 weeks after delivery in order to maintain the early metabolic activation. During the first postnatal day, GLUT1 is strongly induced in the upper region of the third ventricle and in the ventral area of the rostral cerebral aqueduct. During the next 4 days, GLUT1 is expressed in all differentiated ependymal cells of the third ventricle and in hypothalamic tanycytes. At the end of the first week, ependymal cell differentiation and GLUT1 overexpression is concentrated in the latero-ventral area of the aqueduct. We propose that ependymal cell differentiation and GLUT1 overexpression is a synchronous process in the ventricular wall.