32 results on '"Amanda Wyatt"'
Search Results
2. Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice
- Author
-
Sen Qiao, Samer Alasmi, Amanda Wyatt, Philipp Wartenberg, Hongmei Wang, Michael Candlish, Debajyoti Das, Mari Aoki, Ramona Grünewald, Ziyue Zhou, Qinghai Tian, Qiang Yu, Viktoria Götz, Anouar Belkacemi, Ahsan Raza, Fabien Ectors, Kathrin Kattler, Gilles Gasparoni, Jörn Walter, Peter Lipp, Patrice Mollard, Daniel J. Bernard, Ersin Karatayli, Senem Ceren Karatayli, Frank Lammert, and Ulrich Boehm
- Subjects
Science - Abstract
Gonadotropes in the pituitary secrete follicle-stimulating hormone and luteinizing hormone to control gonadal function and fertility, but whether they exert actions on extra-gonadal organs is not fully understood. Here the authors report that gonadotropes regulate liver steatosis independent of the ovaries in mice.
- Published
- 2023
- Full Text
- View/download PDF
3. Ovulation is triggered by a cyclical modulation of gonadotropes into a hyperexcitable state
- Author
-
Viktoria Götz, Sen Qiao, Debajyoti Das, Philipp Wartenberg, Amanda Wyatt, Vanessa Wahl, Igor Gamayun, Samer Alasmi, Claudia Fecher-Trost, Markus R. Meyer, Roland Rad, Thorsten Kaltenbacher, Kathrin Kattler, Peter Lipp, Ute Becherer, Patrice Mollard, Michael Candlish, and Ulrich Boehm
- Subjects
CP: Developmental biology ,Biology (General) ,QH301-705.5 - Abstract
Summary: Gonadotropes in the anterior pituitary gland are essential for fertility and provide a functional link between the brain and the gonads. To trigger ovulation, gonadotrope cells release massive amounts of luteinizing hormone (LH). The mechanism underlying this remains unclear. Here, we utilize a mouse model expressing a genetically encoded Ca2+ indicator exclusively in gonadotropes to dissect this mechanism in intact pituitaries. We demonstrate that female gonadotropes exclusively exhibit a state of hyperexcitability during the LH surge, resulting in spontaneous [Ca2+]i transients in these cells, which persist in the absence of any in vivo hormonal signals. L-type Ca2+ channels and transient receptor potential channel A1 (TRPA1) together with intracellular reactive oxygen species (ROS) levels ensure this state of hyperexcitability. Consistent with this, virus-assisted triple knockout of Trpa1 and L-type Ca2+ subunits in gonadotropes leads to vaginal closure in cycling females. Our data provide insight into molecular mechanisms required for ovulation and reproductive success in mammals.
- Published
- 2023
- Full Text
- View/download PDF
4. Lung emphysema and impaired macrophage elastase clearance in mucolipin 3 deficient mice
- Author
-
Barbara Spix, Elisabeth S. Butz, Cheng-Chang Chen, Anna Scotto Rosato, Rachel Tang, Aicha Jeridi, Veronika Kudrina, Eva Plesch, Philipp Wartenberg, Elisabeth Arlt, Daria Briukhovetska, Meshal Ansari, Gizem Günes Günsel, Thomas M. Conlon, Amanda Wyatt, Sandra Wetzel, Daniel Teupser, Lesca M. Holdt, Fabien Ectors, Ingrid Boekhoff, Ulrich Boehm, Jaime García-Añoveros, Paul Saftig, Martin Giera, Sebastian Kobold, Herbert B. Schiller, Susanna Zierler, Thomas Gudermann, Christian Wahl-Schott, Franz Bracher, Ali Önder Yildirim, Martin Biel, and Christian Grimm
- Subjects
Science - Abstract
Excess macrophage elastase MMP-12 is a major driver of chronic obstructive pulmonary disease. Here the authors show that the endolysosomal ion channel TRPML3 is a regulator of the cellular reuptake of MMP-12, thus neutralizing harmful MMP-12 in the lung.
- Published
- 2022
- Full Text
- View/download PDF
5. TPC2 rescues lysosomal storage in mucolipidosis type IV, Niemann–Pick type C1, and Batten disease
- Author
-
Anna Scotto Rosato, Einar K Krogsaeter, Dawid Jaślan, Carla Abrahamian, Sandro Montefusco, Chiara Soldati, Barbara Spix, Maria Teresa Pizzo, Giuseppina Grieco, Julia Böck, Amanda Wyatt, Daniela Wünkhaus, Marcel Passon, Marc Stieglitz, Marco Keller, Guido Hermey, Sandra Markmann, Doris Gruber‐Schoffnegger, Susan Cotman, Ludger Johannes, Dennis Crusius, Ulrich Boehm, Christian Wahl‐Schott, Martin Biel, Franz Bracher, Elvira De Leonibus, Elena Polishchuk, Diego L Medina, Dominik Paquet, and Christian Grimm
- Subjects
Batten ,MLIV ,NPC1 ,TPC2 ,TRPML ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Abstract Lysosomes are cell organelles that degrade macromolecules to recycle their components. If lysosomal degradative function is impaired, e.g., due to mutations in lysosomal enzymes or membrane proteins, lysosomal storage diseases (LSDs) can develop. LSDs manifest often with neurodegenerative symptoms, typically starting in early childhood, and going along with a strongly reduced life expectancy and quality of life. We show here that small molecule activation of the Ca2+‐permeable endolysosomal two‐pore channel 2 (TPC2) results in an amelioration of cellular phenotypes associated with LSDs such as cholesterol or lipofuscin accumulation, or the formation of abnormal vacuoles seen by electron microscopy. Rescue effects by TPC2 activation, which promotes lysosomal exocytosis and autophagy, were assessed in mucolipidosis type IV (MLIV), Niemann–Pick type C1, and Batten disease patient fibroblasts, and in neurons derived from newly generated isogenic human iPSC models for MLIV and Batten disease. For in vivo proof of concept, we tested TPC2 activation in the MLIV mouse model. In sum, our data suggest that TPC2 is a promising target for the treatment of different types of LSDs, both in vitro and in‐vivo.
- Published
- 2022
- Full Text
- View/download PDF
6. Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection
- Author
-
Monika I. Hollenhorst, Rajender Nandigama, Saskia B. Evers, Igor Gamayun, Noran Abdel Wadood, Alaa Salah, Mario Pieper, Amanda Wyatt, Alexey Stukalov, Anna Gebhardt, Wiebke Nadolni, Wera Burow, Christian Herr, Christoph Beisswenger, Soumya Kusumakshi, Fabien Ectors, Tatjana I. Kichko, Lisa Hübner, Peter Reeh, Antje Munder, Sandra-Maria Wienhold, Martin Witzenrath, Robert Bals, Veit Flockerzi, Thomas Gudermann, Markus Bischoff, Peter Lipp, Susanna Zierler, Vladimir Chubanov, Andreas Pichlmair, Peter König, Ulrich Boehm, and Gabriela Krasteva-Christ
- Subjects
Immunology ,Pulmonology ,Medicine - Abstract
Constant exposure of the airways to inhaled pathogens requires efficient early immune responses protecting against infections. How bacteria on the epithelial surface are detected and first-line protective mechanisms are initiated are not well understood. We have recently shown that tracheal brush cells (BCs) express functional taste receptors. Here we report that bitter taste signaling in murine BCs induces neurogenic inflammation. We demonstrate that BC signaling stimulates adjacent sensory nerve endings in the trachea to release the neuropeptides CGRP and substance P that mediate plasma extravasation, neutrophil recruitment, and diapedesis. Moreover, we show that bitter tasting quorum-sensing molecules from Pseudomonas aeruginosa activate tracheal BCs. BC signaling depends on the key taste transduction gene Trpm5, triggers secretion of immune mediators, among them the most abundant member of the complement system, and is needed to combat P. aeruginosa infections. Our data provide functional insight into first-line defense mechanisms against bacterial infections of the lung.
- Published
- 2022
- Full Text
- View/download PDF
7. Acute Downregulation but Not Genetic Ablation of Murine MCU Impairs Suppressive Capacity of Regulatory CD4 T Cells
- Author
-
Priska Jost, Franziska Klein, Benjamin Brand, Vanessa Wahl, Amanda Wyatt, Daniela Yildiz, Ulrich Boehm, Barbara A. Niemeyer, Martin Vaeth, and Dalia Alansary
- Subjects
mitochondrial calcium uniporter ,regulatory T cells ,suppressive capacity ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
By virtue of mitochondrial control of energy production, reactive oxygen species (ROS) generation, and maintenance of Ca2+ homeostasis, mitochondria play an essential role in modulating T cell function. The mitochondrial Ca2+ uniporter (MCU) is the pore-forming unit in the main protein complex mediating mitochondrial Ca2+ uptake. Recently, MCU has been shown to modulate Ca2+ signals at subcellular organellar interfaces, thus fine-tuning NFAT translocation and T cell activation. The mechanisms underlying this modulation and whether MCU has additional T cell subpopulation-specific effects remain elusive. However, mice with germline or tissue-specific ablation of Mcu did not show impaired T cell responses in vitro or in vivo, indicating that ‘chronic’ loss of MCU can be functionally compensated in lymphocytes. The current work aimed to specifically investigate whether and how MCU influences the suppressive potential of regulatory CD4 T cells (Treg). We show that, in contrast to genetic ablation, acute siRNA-mediated downregulation of Mcu in murine Tregs results in a significant reduction both in mitochondrial Ca2+ uptake and in the suppressive capacity of Tregs, while the ratios of Treg subpopulations and the expression of hallmark transcription factors were not affected. These findings suggest that permanent genetic inactivation of MCU may result in compensatory adaptive mechanisms, masking the effects on the suppressive capacity of Tregs.
- Published
- 2023
- Full Text
- View/download PDF
8. Combining mass spectrometry and genetic labeling in mice to report TRP channel expression
- Author
-
Philipp Wartenberg, Femke Lux, Kai Busch, Claudia Fecher-Trost, Amanda Wyatt, Veit Flockerzi, Gabriela Krasteva-Christ, Ulrich Boehm, and Petra Weissgerber
- Subjects
TRP expression ,Genetic labeling ,Mass spectrometry ,Immunoprecipitation ,Science - Abstract
Transient receptor potential (TRP) ion channels play important roles in fundamental biological processes throughout the body of humans and mice. TRP channel dysfunction manifests in different disease states, therefore, these channels may represent promising therapeutic targets in treating these conditions. Many TRP channels are expressed in several organs suggesting multiple functions and making it challenging to untangle the systemic pathophysiology of TRP dysfunction. Detailed characterization of the expression pattern of the individual TRP channels throughout the organism is thus essential to interpret data such as those derived from systemic phenotyping of global TRP knockout mice. Murine TRP channel reporter strains enable reliable labeling of TRP expression with a fluorescent marker. Here we present an optimized method to visualize primary TRP-expressing cells with single cell resolution throughout the entire organism. In parallel, we methodically combine systemic gene expression profiling with an adjusted mass spectrometry protocol to document acute protein levels in selected organs of interest. The TRP protein expression data are then correlated with the GFP reporter expression data. The combined methodological approach presented here can be adopted to generate expression data for other genes of interest and reporter mice. • We present an optimized method to systemically characterize gene expression in fluorescent reporter mouse strains with a single cell resolution. • We methodically combine systemic gene expression profiling with an adjusted mass spectrometry protocol to document acute protein levels in selected organs of interest in mice.
- Published
- 2022
- Full Text
- View/download PDF
9. TRPC channels regulate Ca2+-signaling and short-term plasticity of fast glutamatergic synapses.
- Author
-
Yvonne Schwarz, Katharina Oleinikov, Barbara Schindeldecker, Amanda Wyatt, Petra Weißgerber, Veit Flockerzi, Ulrich Boehm, Marc Freichel, and Dieter Bruns
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Transient receptor potential (TRP) proteins form Ca2+-permeable, nonselective cation channels, but their role in neuronal Ca2+ homeostasis is elusive. In the present paper, we show that TRPC channels potently regulate synaptic plasticity by changing the presynaptic Ca2+-homeostasis of hippocampal neurons. Specifically, loss of TRPC1/C4/C5 channels decreases basal-evoked secretion, reduces the pool size of readily releasable vesicles, and accelerates synaptic depression during high-frequency stimulation (HFS). In contrast, primary TRPC5 channel-expressing neurons, identified by a novel TRPC5-τ-green fluorescent protein (τGFP) knockin mouse line, show strong short-term enhancement (STE) of synaptic signaling during HFS, indicating a key role of TRPC5 in short-term plasticity. Lentiviral expression of either TRPC1 or TRPC5 turns classic synaptic depression of wild-type neurons into STE, demonstrating that TRPCs are instrumental in regulating synaptic plasticity. Presynaptic Ca2+ imaging shows that TRPC activity strongly boosts synaptic Ca2+ dynamics, showing that TRPC channels provide an additional presynaptic Ca2+ entry pathway, which efficiently regulates synaptic strength and plasticity.
- Published
- 2019
- Full Text
- View/download PDF
10. Using Outcome Trajectory Evaluation to Assess HarvestPlus' Contribution to the Development of National Biofortification Breeding Programs
- Author
-
Boru Douthwaite, Nancy Johnson, and Amanda Wyatt
- Subjects
Geography, Planning and Development ,Development - Abstract
Improving policies-broadly defined-is at the heart of the structural transformation agenda. This paper describes the use of a new evaluation method-outcome trajectory evaluation (OTE), based on both evaluation and policy process theory-to explore the influence of HarvestPlus, a large and complex research for development program focused on improving nutrition, on a specific policy outcome, namely the establishment of biofortification crop breeding programs in national agricultural research institutes in Bangladesh, India, and Rwanda. The findings support claims of significant HarvestPlus contributions while also raising issues that need to be monitored to ensure sustainability. The paper also discusses the pros and cons of the OTE approach in terms of methodological rigor and the accumulation of learning from one evaluation to the next.L'amélioration des politiques, au sens large, est au cœur du programme de transformation structurelle. Cet article décrit l'utilisation d'une nouvelle méthode d'évaluation - l'évaluation de la trajectoire des résultats (outcome trajectory evaluation ou OTE en anglais), basée à la fois sur la théorie de l’évaluation et du processus politique - pour explorer l'influence de HarvestPlus, un vaste et complexe programme de recherche pour le développement axé sur l'amélioration de la nutrition, et orienté vers un résultat politique, à savoir la mise en place de programmes de biofortification et de sélection de cultures dans les instituts nationaux de recherche agricole au Bangladesh, en Inde et au Rwanda. Les résultats appuient les allégations selon lesquelles HarvestPlus permet des contributions importantes, tout en soulevant des problèmes qui doivent être surveillés pour assurer la durabilité. L'article discute également des avantages et des inconvénients de l'approche OTE en termes de rigueur méthodologique et d'accumulation d'apprentissage d'une évaluation à l'autre.
- Published
- 2022
11. Whole-body analysis of TRPML3 (MCOLN3) expression using a GFP-reporter mouse model reveals widespread expression in secretory cells and endocrine glands
- Author
-
Barbara Spix, Andrew J. Castiglioni, Natalie N. Remis, Emma N. Flores, Philipp Wartenberg, Amanda Wyatt, Ulrich Boehm, Thomas Gudermann, Martin Biel, Jaime García-Añoveros, and Christian Grimm
- Subjects
Multidisciplinary - Abstract
TRPML3 (mucolipin 3, MCOLN3) is an endolysosomal cation channel belonging to the TRPML subfamily of transient receptor potential channels. Gain-of-function mutations in the Trpml3 gene cause deafness, circling behavior and coat color dilution in mice due to cell death of TRPML3-expressing hair cells of the inner ear or skin melanocytes, respectively. Furthermore, TRPML3 was found to play a role in the long term survival of cochlear hair cells (its absence contributing to presbycusis), in specialized giant lysosomes that neonatal (birth to weaning) enterocytes used for the uptake and digestion of maternal milk nutrients, and in the expulsion of exosome-encased bacteria such as uropathogenic E. coli, infecting bladder epithelial cells. Recently, TRPML3 was found to be expressed at high levels in alveolar macrophages and loss of TRPML3 results in a lung emphysema phenotype, confirmed in two independently engineered Trpml3 knockout lines. TRPML3 is not ubiquitously expressed like its relative TRPML1 and thus cellular expression of TRPML3 on a whole-tissue level remains, with the exceptions mentioned above, largely elusive. To overcome this problem, we generated a τGFP reporter mouse model for TRPML3 and compared expression data obtained from this model by immunofluorescence on tissue sections with immunohistochemistry using TRPML3 antibodies and in situ hybridization. We thus uncovered expression in several organs and distinct cell types. We confirmed TRPML3 expression in both neonatal and adult alveolar macrophages, in melanocytes of hair follicles and glabrous skin, in principle cells of the collecting duct of the neonatal and adult kidney, and in olfactory sensory neurons of the olfactory epithelium, including its fibres protruding to the glomeruli of the olfactory bulb. Additionally, we localized TRPML3 in several glands including parathyroid, thyroid, salivary, adrenal, and pituitary gland, testes and ovaries, suggestive of potential roles for the channel in secretion or uptake of different hormones.
- Published
- 2022
12. <scp>TPC2</scp> rescues lysosomal storage in mucolipidosis type <scp>IV</scp> , <scp>Niemann–Pick</scp> type <scp>C1,</scp> and Batten disease
- Author
-
Anna Scotto Rosato, Einar K Krogsaeter, Dawid Jaślan, Carla Abrahamian, Sandro Montefusco, Chiara Soldati, Barbara Spix, Maria Teresa Pizzo, Giuseppina Grieco, Julia Böck, Amanda Wyatt, Daniela Wünkhaus, Marcel Passon, Marc Stieglitz, Marco Keller, Guido Hermey, Sandra Markmann, Doris Gruber‐Schoffnegger, Susan Cotman, Ludger Johannes, Dennis Crusius, Ulrich Boehm, Christian Wahl‐Schott, Martin Biel, Franz Bracher, Elvira De Leonibus, Elena Polishchuk, Diego L Medina, Dominik Paquet, Christian Grimm, Scotto Rosato, Anna, Krogsaeter, Einar K, Jaślan, Dawid, Abrahamian, Carla, Montefusco, Sandro, Soldati, Chiara, Spix, Barbara, Pizzo, Maria Teresa, Grieco, Giuseppina, Böck, Julia, Wyatt, Amanda, Wünkhaus, Daniela, Passon, Marcel, Stieglitz, Marc, Keller, Marco, Hermey, Guido, Markmann, Sandra, Gruber-Schoffnegger, Dori, Cotman, Susan, Johannes, Ludger, Crusius, Denni, Boehm, Ulrich, Wahl-Schott, Christian, Biel, Martin, Bracher, Franz, De Leonibus, Elvira, Polishchuk, Elena, Medina, Diego Lui, Paquet, Dominik, and Grimm, Christian
- Subjects
MLIV ,Animal ,Mucolipidose ,TPC2 ,Lysosome ,NPC1 ,Lysosomal Storage Diseases ,Mice ,Lysosomal Storage Disease ,Mucolipidoses ,Neuronal Ceroid-Lipofuscinoses ,Batten ,Child, Preschool ,Quality of Life ,Animals ,Humans ,Molecular Medicine ,TRPML ,Lysosomes ,Human - Abstract
Lysosomes are cell organelles that degrade macromolecules to recycle their components. If lysosomal degradative function is impaired, e.g., due to mutations in lysosomal enzymes or membrane proteins, lysosomal storage diseases (LSDs) can develop. LSDs manifest often with neurodegenerative symptoms, typically starting in early childhood, and going along with a strongly reduced life expectancy and quality of life. We show here that small molecule activation of the Ca2+ -permeable endolysosomal two-pore channel 2 (TPC2) results in an amelioration of cellular phenotypes associated with LSDs such as cholesterol or lipofuscin accumulation, or the formation of abnormal vacuoles seen by electron microscopy. Rescue effects by TPC2 activation, which promotes lysosomal exocytosis and autophagy, were assessed in mucolipidosis type IV (MLIV), Niemann-Pick type C1, and Batten disease patient fibroblasts, and in neurons derived from newly generated isogenic human iPSC models for MLIV and Batten disease. For in vivo proof of concept, we tested TPC2 activation in the MLIV mouse model. In sum, our data suggest that TPC2 is a promising target for the treatment of different types of LSDs, both in vitro and in-vivo.
- Published
- 2022
13. Using outcome trajectory evaluation to assess HarvestPlus’ contribution to the development of national biofortification breeding programs
- Author
-
Amanda Wyatt, Nancy L. Johnson, and Boru Douthwaite
- Published
- 2022
14. Prolactin-sensitive olfactory sensory neurons regulate male preference in female mice by modulating responses to chemosensory cues
- Author
-
Jörn Walter, Gilles Gasparoni, Oliver Hummel, Igor Gamayun, Amanda Wyatt, Stefan Wagenpfeil, Ulrich Boehm, David R. Grattan, Stephan E. Philipp, Mari Aoki, Ramona Grünewald, Martin Simon-Thomas, Kathrin Kattler, and Sen Qiao
- Subjects
Multidisciplinary ,Prolactin receptor ,SciAdv r-articles ,Sensory system ,Biology ,Prolactin ,medicine.anatomical_structure ,medicine ,Biological neural network ,Endocrine system ,Receptor ,Neuroscience ,Nose ,Hormone ,Research Article - Abstract
Description, Prolactin modulates the detection of olfactory signals in female mice to enhance preference toward males., Chemosensory cues detected in the nose need to be integrated with the hormonal status to trigger appropriate behaviors, but the neural circuits linking the olfactory and the endocrine system are insufficiently understood. Here, we characterize olfactory sensory neurons in the murine nose that respond to the pituitary hormone prolactin. Deletion of prolactin receptor in these cells results in impaired detection of social odors and blunts male preference in females. The prolactin-responsive olfactory sensory neurons exhibit a distinctive projection pattern to the brain that is similar across different individuals and express a limited subset of chemosensory receptors. Prolactin modulates the responses within these neurons to discrete chemosensory cues contained in male urine, providing a mechanism by which the hormonal status can be directly linked with distinct olfactory cues to generate appropriate behavioral responses.
- Published
- 2021
15. Subunit composition, molecular environment, and activation of native TRPC channels encoded by their interactomes
- Author
-
Astrid Kollewe, Yvonne Schwarz, Katharina Oleinikov, Ahsan Raza, Alexander Haupt, Philipp Wartenberg, Amanda Wyatt, Ulrich Boehm, Fabien Ectors, Wolfgang Bildl, Gerd Zolles, Uwe Schulte, Dieter Bruns, Veit Flockerzi, and Bernd Fakler
- Subjects
General Neuroscience - Abstract
In the mammalian brain TRPC channels, a family of Ca
- Published
- 2022
16. A community-based sleep educational intervention for children with autism spectrum disorder
- Author
-
David Schlund, Whitney A. Loring, Kemberlee Bonnet, Laura Gray, Lydia L. MacDonald, Mary Landis Gaston, Amanda Wyatt, and Beth A. Malow
- Subjects
030506 rehabilitation ,education.field_of_study ,05 social sciences ,Population ,Actigraphy ,medicine.disease ,Article ,03 medical and health sciences ,Psychiatry and Mental health ,Clinical Psychology ,Autism spectrum disorder ,Intervention (counseling) ,Developmental and Educational Psychology ,medicine ,Autism ,0501 psychology and cognitive sciences ,Sleep onset ,0305 other medical science ,education ,Child Behavior Checklist ,Psychology ,Curriculum ,050104 developmental & child psychology ,Clinical psychology - Abstract
Background Sleep problems are common in children with autism spectrum disorder (ASD). Sleep education, effective in improving sleep in ASD, may be difficult to access. We determined if community-based pediatric therapists could successfully deliver sleep educational interventions to caregivers of children with ASD. Methods A seven-week feasibility study was conducted consisting of 10 children and caregivers. This feasibility study informed the development of a 16-week preliminary effectiveness study, which consisted of 33 children and caregivers. Children, ages 2–12 years, with a clinical diagnosis of autism and caregiver-reported sleep onset delay of 30 min were included. Community therapists underwent comprehensive training in sleep education and then met with caregiver participants to provide sleep education to each family. Semi-structured qualitative interviews were conducted with all families who completed study procedures. In the feasibility and preliminary effectiveness studies, child participants wore an actigraphy watch (at baseline and after sleep education) and caregivers completed the Child Sleep Habits Questionnaire and Family Inventory of Sleep Habits at baseline and after sleep education; the Child Behavior Checklist was also completed by caregivers in the preliminary effectiveness study. Results Educator fidelity to the manualized curriculum was maintained. Caregivers showed appropriate understanding, comfort, and implementation of the curriculum. Qualitative and quantitative measures, including caregiver surveys and actigraphy, showed improvements in child sleep and behavior. Conclusions Community-based therapists can successfully deliver sleep education to families of children with ASD, which has favorable implications for improving access to care in this population.
- Published
- 2021
17. Human TRPV6-pathies caused by gene mutations
- Author
-
Amanda Wyatt, Verena Nett, Nicole Erhardt, and Ulrich Wissenbach
- Subjects
0301 basic medicine ,TRPV6 ,TRPV5 ,Biophysics ,Parathyroid hormone ,TRPV Cation Channels ,Gene mutation ,Biochemistry ,03 medical and health sciences ,Transient receptor potential channel ,0302 clinical medicine ,medicine ,Humans ,Molecular Biology ,Ion channel ,TRPV6 Gene ,Hyperparathyroidism ,Chemistry ,medicine.disease ,Molecular biology ,030104 developmental biology ,Mutation ,Calcium ,Channelopathies ,Calcium Channels ,030217 neurology & neurosurgery - Abstract
The TRP-family of ion channels consists of 27 members in humans. Most TRP channels are non- selective cation channels with the exception of TRPV5 and TRPV6 which exhibit a high permeability for Ca2+ ions. A functional channel is formed by 4 identical subunits [1]. A growing number of mutations are present in human TRPV6 genes which alter channel function and can lead to elevated blood levels of the parathyroid hormone accompanied by transient hyperparathyroidism. Recent publications suggest that TRPV6 mutations could also trigger non-alcoholic chronic pancreatitis. This review summarises the consequences of these mutations within the TRPV6 gene.
- Published
- 2020
18. Comments on the evolution of TRPV6
- Author
-
Amanda Wyatt, Karin Wolske, and Ulrich Wissenbach
- Subjects
0301 basic medicine ,TRPV6 Gene ,Genetics ,TRPV5 ,Placenta ,TRPV Cation Channels ,Translation (biology) ,General Medicine ,Biology ,Genome ,Mice ,03 medical and health sciences ,Transient receptor potential channel ,030104 developmental biology ,Pregnancy ,Gene duplication ,Animals ,Calcium ,Female ,Calcium Channels ,030101 anatomy & morphology ,Anatomy ,Allele ,Ion channel ,Developmental Biology - Abstract
It is well known that not all biological findings derived from animals can be directly applied to humans. The TRPV6 protein may serve as an example which highlights these inter-species differences as an example of parallel evolutionary pathways. TRPV6 (and TRPV5) belong to a family of ion channels from the transient receptor potential group but are selectively permeable for Ca2+, in contrast to other members of the family. Sequences with recognizable similarity to TRPV6 can already be found in archaebacteria. These ancient sequences show clear similarity to the ion-conducting pore of TRPV6. Over the course of evolution, the duplication of the TRPV6 gene gave rise to TRPV5. Duplications of the complete genome as well as subsequent loss of genetic material have led to a variety of different TRPV5/6 combinations. In addition, there is an N-terminal extension of the protein in placental animals. This extension causes translation of TRPV6 to be initiated from an ACG codon. Inactivation of one TRPV6 allele can be correlated with alcohol-independent pancreatitis in humans while inactivation of both alleles leads to skeletal dysplasia of newborn babies. The latter effect is not observed in mice, implying that the effects due to perturbations in TRPV6 levels are much more pronounced in humans.
- Published
- 2021
19. Genetic strategies to analyze primary TRP channel-expressing cells in mice
- Author
-
Michael Candlish, Gabriela Krasteva-Christ, Amanda Wyatt, Philipp Wartenberg, Ulrich Boehm, and Veit Flockerzi
- Subjects
0301 basic medicine ,Aging ,RNA, Untranslated ,Physiology ,Green Fluorescent Proteins ,TRPM Cation Channels ,Cre recombinase ,Mice, Transgenic ,Biology ,TRPC1 ,Mice ,03 medical and health sciences ,Transient receptor potential channel ,Gene knockin ,Animals ,Protein Isoforms ,Gene Knock-In Techniques ,TRPM5 ,Homologous Recombination ,Molecular Biology ,Ion channel ,Genetics ,Integrases ,Gene targeting ,Cell Biology ,Founder Effect ,Cell biology ,030104 developmental biology ,Gene Expression Regulation ,Single-Cell Analysis ,Function (biology) ,Signal Transduction - Abstract
Transient receptor potential (TRP) ion channels regulate fundamental biological processes throughout the body. TRP channel dysfunction has been causally linked to a number of disease states and thus establishes these channels as promising therapeutic targets. In order to dissect the physiological role of individual TRP channels in specific tissues, a detailed understanding of the expression pattern of the different TRP channels throughout the organism is essential. We provide an overview of recent efforts to generate novel TRP channel reporter mouse strains for all 28 TRP channels encoded in the mouse genome to understand expression of these channels with a single-cell resolution in an organism-wide manner. The reporter mice will enable both the visualization and manipulation of all primary TRP channel-expressing cells allowing an unprecedented wealth in variety to investigate TRP channel function in vivo. As proof of principle, we provide preliminary results documenting TRPM5 expression throughout the entire body of juvenile and adult mice.
- Published
- 2017
20. TRPC channels regulate Ca2+-signaling and short-term plasticity of fast glutamatergic synapses
- Author
-
Veit Flockerzi, Katharina Oleinikov, Barbara Schindeldecker, Dieter Bruns, Ulrich Boehm, Amanda Wyatt, Yvonne Schwarz, Marc Freichel, and Petra Weißgerber
- Subjects
0301 basic medicine ,Male ,Physiology ,Glutamine ,TRPC5 ,Biochemistry ,Nervous System ,Hippocampus ,Ion Channels ,TRPC1 ,Transient receptor potential channel ,0302 clinical medicine ,Transient Receptor Potential Channels ,Animal Cells ,Medicine and Health Sciences ,Biology (General) ,TRPC ,Calcium signaling ,Neurons ,Mice, Knockout ,Neuronal Plasticity ,Depression ,General Neuroscience ,Physics ,Electrophysiology ,Physical Sciences ,Female ,Synaptic signaling ,Cellular Types ,Cellular Structures and Organelles ,Anatomy ,General Agricultural and Biological Sciences ,Research Article ,QH301-705.5 ,Receptor potential ,Biophysics ,Neurophysiology ,Biology ,Membrane Potential ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Developmental Neuroscience ,Receptor Potentials ,Mental Health and Psychiatry ,Animals ,Vesicles ,Calcium Signaling ,TRPC Cation Channels ,General Immunology and Microbiology ,Mood Disorders ,Biology and Life Sciences ,Proteins ,Cell Biology ,030104 developmental biology ,Cellular Neuroscience ,Synaptic plasticity ,Synapses ,Calcium Channels ,Neuroscience ,030217 neurology & neurosurgery ,Synaptic Plasticity - Abstract
Transient receptor potential (TRP) proteins form Ca2+-permeable, nonselective cation channels, but their role in neuronal Ca2+ homeostasis is elusive. In the present paper, we show that TRPC channels potently regulate synaptic plasticity by changing the presynaptic Ca2+-homeostasis of hippocampal neurons. Specifically, loss of TRPC1/C4/C5 channels decreases basal-evoked secretion, reduces the pool size of readily releasable vesicles, and accelerates synaptic depression during high-frequency stimulation (HFS). In contrast, primary TRPC5 channel-expressing neurons, identified by a novel TRPC5–τ-green fluorescent protein (τGFP) knockin mouse line, show strong short-term enhancement (STE) of synaptic signaling during HFS, indicating a key role of TRPC5 in short-term plasticity. Lentiviral expression of either TRPC1 or TRPC5 turns classic synaptic depression of wild-type neurons into STE, demonstrating that TRPCs are instrumental in regulating synaptic plasticity. Presynaptic Ca2+ imaging shows that TRPC activity strongly boosts synaptic Ca2+ dynamics, showing that TRPC channels provide an additional presynaptic Ca2+ entry pathway, which efficiently regulates synaptic strength and plasticity., Transient receptor potential (TRP) proteins can form non-selective cation channels, but their role in synaptic transmission is poorly understood. This study shows that calcium-permeable TRPC channels provide an additional calcium entry pathway at presynaptic sites and are efficient regulators of synaptic strength and plasticity.
- Published
- 2019
21. Widespread Cell-Specific Prolactin Receptor Expression in Multiple Murine Organs
- Author
-
Hollian R Phillipps, David R. Grattan, Mari Aoki, Philipp Wartenberg, Amanda Wyatt, Ulrich Boehm, and Ramona Grünewald
- Subjects
Gene isoform ,Male ,medicine.medical_specialty ,Receptors, Prolactin ,Cell ,Respiratory System ,Cre recombinase ,Urogenital System ,Biology ,Green fluorescent protein ,Lymphatic System ,Mice ,Endocrinology ,Exocrine Glands ,Internal medicine ,Endocrine Glands ,medicine ,Animals ,Receptor ,Prolactin receptor ,Prolactin ,Cell biology ,Gastrointestinal Tract ,Internal ribosome entry site ,medicine.anatomical_structure ,Female - Abstract
The prolactin receptor (Prlr) mediates not only the multiple effects of prolactin, but also those of the placental lactogens and, in humans, some actions of growth hormone. Although Prlr expression has been reported to be widespread in the body, specific cellular expression patterns within tissues are undefined for many organs. One persisting problem in investigating Prlr function is that the protein is difficult to detect using conventional methods. To allow investigation of Prlr expression with a single cell resolution, we have recently developed a knock-in mouse strain in which Cre recombinase is expressed together with the long isoform of the Prlr using an internal ribosome entry site. When crossed to a Cre-dependent reporter mouse strain, Cre-mediated recombination will genetically label cells that acutely express the Prlr as well as cells that have transiently expressed the Prlr during development. We report here the anatomical distribution of cells which express the fluorescent reporter τ green fluorescent protein in a total of 38 organs prepared from young adult male and female Prlr reporter mice. Our results establish a resource for dissecting the functional role of Prlr in multiple murine tissues.
- Published
- 2019
22. Conditional Deletion of the Prolactin Receptor Reveals Functional Subpopulations of Dopamine Neurons in the Arcuate Nucleus of the Hypothalamus
- Author
-
Amanda Wyatt, Sharon R Ladyman, Papillon Gustafson, Hollian R Phillipps, Paul LeTissier, Caroline M. Larsen, David R. Grattan, Ilona C. Kokay, Penelope J. Knowles, Rosemary S E Brown, and Siew Hoong Yip
- Subjects
Male ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,RNA, Untranslated ,Receptors, Prolactin ,Green Fluorescent Proteins ,Radioimmunoassay ,Mice, Transgenic ,Biology ,Statistics, Nonparametric ,Prolactin cell ,03 medical and health sciences ,0302 clinical medicine ,Dopamine ,Arcuate nucleus ,Internal medicine ,STAT5 Transcription Factor ,medicine ,Animals ,RNA, Messenger ,gamma-Aminobutyric Acid ,Tyrosine hydroxylase ,Glutamate Decarboxylase ,Dopaminergic Neurons ,General Neuroscience ,Prolactin receptor ,Arcuate Nucleus of Hypothalamus ,Articles ,Prolactin ,Rats ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,nervous system ,Hypothalamus ,GABAergic ,Female ,030217 neurology & neurosurgery ,medicine.drug - Abstract
UNLABELLED: Tuberoinfundibular dopamine (TIDA) neurons, known as neuroendocrine regulators of prolactin secretion from the pituitary gland, also release GABA within the hypothalamic arcuate nucleus. As these neurons express prolactin receptors (Prlr), prolactin may regulate GABA secretion from TIDA neurons, potentially mediating actions of prolactin on hypothalamic function. To investigate whether GABA is involved in feedback regulation of TIDA neurons, we examined the physiological consequences of conditional deletion of Prlr in GABAergic neurons. For comparison, we also examined mice in which Prlr were deleted from most forebrain neurons. Both neuron-specific and GABA-specific recombination of the Prlr gene occurred throughout the hypothalamus and in some extrahypothalamic regions, consistent with the known distribution of Prlr expression, indicative of knock-out of Prlr. This was confirmed by a significant loss of prolactin-induced phosphorylation of STAT5, a marker of prolactin action. Several populations of GABAergic neurons that were not previously known to be prolactin-sensitive, notably in the medial amygdala, were identified. Approximately 50% of dopamine neurons within the arcuate nucleus were labeled with a GABA-specific reporter, but Prlr deletion from these dopamine/GABA neurons had no effect on feedback regulation of prolactin secretion. In contrast, Prlr deletion from all dopamine neurons resulted in profound hyperprolactinemia. The absence of coexpression of tyrosine hydroxylase, a marker for dopamine production, in GABAergic nerve terminals in the median eminence suggested that rather than a functional redundancy within the TIDA population, the dopamine/GABA neurons in the arcuate nucleus represent a subpopulation with a functional role distinct from the regulation of prolactin secretion.SIGNIFICANCE STATEMENT: Using a novel conditional deletion of the prolactin receptor, we have identified functional subpopulations in hypothalamic dopamine neurons. Although commonly considered a uniform population of neuroendocrine neurons involved in the control of prolactin secretion, we have shown that approximately half of these neurons express GABA as well as dopamine, but these neurons are not necessary for the feedback regulation of prolactin secretion. The absence of tyrosine hydroxylase in GABAergic nerve terminals in the median eminence suggests that only the non-GABAergic dopamine neurons are involved in the control of pituitary prolactin secretion, and the GABAergic subpopulation may function as interneurons within the arcuate nucleus to regulate other aspects of hypothalamic function.
- Published
- 2016
23. Osteoprotective Effects of Estrogen in the Maxillary Bone Depend on ERα
- Author
-
Tarcília Aparecida Silva, Soraia Macari, L. Ajay Sharma, David R. Grattan, Amanda Wyatt, George J. Dias, Gustavo Pompermaier Garlet, Penelope J. Knowles, and Raphael E. Szawka
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Tooth Movement Techniques ,Ovariectomy ,Interleukin-1beta ,Osteoporosis ,Alveolar Bone Loss ,Osteoclasts ,Estrogen receptor ,Apoptosis ,Bone Marrow Cells ,Polymerase Chain Reaction ,Bone remodeling ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Bone cell ,Maxilla ,medicine ,Animals ,General Dentistry ,Dental alveolus ,Extracellular Matrix Proteins ,Osteoblasts ,Tumor Necrosis Factor-alpha ,Chemistry ,Estrogen Receptor alpha ,Spectrometry, X-Ray Emission ,Cell Differentiation ,X-Ray Microtomography ,030206 dentistry ,Periodontium ,Alkaline Phosphatase ,Interleukin-33 ,medicine.disease ,Mice, Inbred C57BL ,Phenotype ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Calcium ,Female ,MAXILA ,Bone Remodeling ,Bone marrow ,Estrogen receptor alpha ,Signal Transduction - Abstract
Estrogen deficiency results in disruption of maxillary alveolar bone microarchitecture. Most of the actions of estrogen in long bones occur via estrogen receptor α (ERα). However, the function of ERα in the maxillary bone has not been defined. We aimed to investigate the role and underlying mechanisms of ERα in the physiological and mechanically induced alveolar bone remodeling in female and male mice. Wild-type (WT) and ERα−/− (ERKOα) mice were subjected to mechanically stimulated bone remodeling by inducing orthodontic tooth movement (OTM). The maxillary bone was analyzed using histomorphometric analysis, micro–computed tomography, quantitative polymerase chain reaction, and energy-dispersive spectroscopy. Bone marrow cells (BMCs) from WT and ERKOα mice were tested for their capacity to differentiate into osteoblasts and osteoclasts. Both male and female ERKOα mice exhibited marked reduction of alveolar bone mass and increased OTM. This response was associated with an increased number of osteoclasts and reduced number of apoptotic cells and osteoblasts in the periodontium and alveolar bone. Consistently, ERKOα mice exhibited lower levels of calcium in bone and increased expression of IL-33 (interleukin-33), TNF-α (tumor necrosis factor α), and IL-1β (interleukin-1β) and decreased expression of dentin matrix acidic phosphoprotein and alkaline phosphatase in periodontal tissues. Moreover, the differentiation of osteoclasts and osteoblasts in vitro was significantly higher in BMCs obtained from ERKOα. ERα is required to maintain the microarchitecture of maxillary alveolar bone. This process is linked to bone cell differentiation and apoptosis, as well as local production of inflammatory molecules such as IL-33, TNF-α, and IL-1β.
- Published
- 2016
24. Prolactin transport into mouse brain is independent of prolactin receptor
- Author
-
Amanda Wyatt, Ryan E. Herbison, Sharon R Ladyman, William A. Banks, Nadine Binart, Rosemary S E Brown, David R. Grattan, and Penelope J. Knowles
- Subjects
Male ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,Receptors, Prolactin ,Biochemistry ,Prolactin cell ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Anterior pituitary ,Internal medicine ,STAT5 Transcription Factor ,Genetics ,medicine ,Animals ,Receptor ,Molecular Biology ,Mice, Knockout ,Neurons ,Chemistry ,Prolactin receptor ,Brain ,Prolactin ,Protein Transport ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Female ,Choroid plexus ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,Biotechnology ,Hormone - Abstract
The anterior pituitary hormone prolactin exerts important physiologic actions in the brain. However, the mechanism by which prolactin crosses the blood-brain barrier and enters the brain is not completely understood. On the basis of high expression of the prolactin receptor in the choroid plexus, it has been hypothesized that the receptor may bind to prolactin in the blood and translocate it into the cerebrospinal fluid (CSF). This study aimed to test this hypothesis by investigating transport of (125)I-labeled prolactin ((125)I-prolactin) into the brain of female mice in the presence and absence of the prolactin receptor (PRLR(-/-)). Peripherally administered prolactin rapidly activates brain neurons, as evidenced by prolactin-induced phosphorylation of signal transducer and activator of transcription 5 (pSTAT5) in neurons within 30 min of administration. The transport of prolactin into the brain was saturable, with transport effectively blocked only by a very high dose of unlabeled ovine prolactin. Transport was regulated, as in lactating mice with chronically elevated levels of prolactin, the rate of (125)I-prolactin transport into the brain was significantly increased compared to nonlactating controls. There was no change in the rate of (125)I-prolactin transport into the brain in PRLR(-/-) mice lacking functional prolactin receptors compared to control mice, indicating transport is independent of the prolactin receptor. These data suggest that prolactin transport into the brain involves another as yet unidentified transporter molecule. Because CSF levels of (125)I-prolactin were very low, even up to 90 min after administration, the data suggest that CSF is not the major route by which blood prolactin gains access to neurons in the brain.
- Published
- 2015
25. 0749 Behavioral Sleep Education in Children with Autism and Insomnia: Partnership with Community Practices
- Author
-
Lydia L. MacDonald, Laura Gray, Diane B. Fawkes, Beth A. Malow, Whitney A. Loring, and Amanda Wyatt
- Subjects
medicine.medical_specialty ,business.industry ,Co-sleeping ,Actigraphy ,medicine.disease ,Bedtime ,Sleep medicine ,Autism spectrum disorder ,Physiology (medical) ,Insomnia ,Medicine ,Anxiety ,Autism ,Neurology (clinical) ,medicine.symptom ,business ,Psychiatry - Published
- 2019
26. The depiction of communication technology in film: Differences by gender and across time 1970–2010
- Author
-
Amanda Wyatt, Jeffrey Toussaint, Michelle Reaves, Jennifer Weddle, Elizabeth Monk-Turner, and Evelyn Dempsey
- Subjects
Engineering ,ComputingMilieux_THECOMPUTINGPROFESSION ,Sociology and Political Science ,business.industry ,media_common.quotation_subject ,Media studies ,Human Factors and Ergonomics ,Gender studies ,Education ,Craft ,Information and Communications Technology ,Perception ,Depiction ,Use of technology ,Business and International Management ,Gender role ,business ,Sampling frame ,media_common - Abstract
The use of technology and how we communicate has changed over time. The present study explores how communication is depicted in film and how this differs by gender and across time. The sampling frame consists of the highest grossing films from 1972 to present day. Data support the proposition that there is more technology based communication in film across time. More men than women are portrayed with technology in film. Furthermore, when women interface with technology, they have a higher incidence of utilizing technology for personal use while men tended to use technology for business purposes. We argue that gender differences in use of technology that is portrayed in film shape personal and societal notions about appropriate gender role construction vis-a-vis technology. Importantly, this research supports the social constructionists theory of technology in society demonstrating how images and messaging can craft specific perceptions of technology and its use.
- Published
- 2014
27. Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior
- Author
-
Sharon R Ladyman, Amanda Wyatt, Mari Aoki, Rosemary S E Brown, Ulrich Boehm, Hollian R Phillipps, and David R. Grattan
- Subjects
0301 basic medicine ,medicine.medical_specialty ,endocrine system ,Offspring ,Receptors, Prolactin ,Mothers ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Internal medicine ,Biological neural network ,medicine ,Animals ,Lactation ,Receptor ,Maternal Behavior ,reproductive and urinary physiology ,Mice, Knockout ,Multidisciplinary ,Behavior, Animal ,Prolactin receptor ,Postpartum Period ,Glutamate receptor ,Biological Sciences ,Preoptic Area ,Prolactin ,Medial preoptic area ,030104 developmental biology ,Endocrinology ,nervous system ,Female ,Psychology ,030217 neurology & neurosurgery ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
Pregnancy hormones, such as prolactin, sensitize neural circuits controlling parental interactions to induce timely activation of maternal behaviors immediately after parturition. While the medial preoptic area (MPOA) is known to be critical for maternal behavior, the specific role of prolactin in this brain region has remained elusive. Here, we evaluated the role of prolactin action in the MPOA using complementary genetic strategies in mice. We characterized prolactin-responsive neurons within the MPOA at different hormonal stages and delineated their projections in the brain. We found that MPOA neurons expressing prolactin receptors (Prlr) form the nexus of a complex prolactin-responsive neural circuit, indicating that changing prolactin levels can act at multiple sites and thus, impinge on the overall activity of a distributed network of neurons. Conditional KO of Prlr from neuronal subpopulations expressing the neurotransmitters GABA or glutamate within this circuit markedly reduced the capacity for prolactin action both in the MPOA and throughout the network. Each of these manipulations, however, produced only subtle impacts on maternal care, suggesting that this distributed circuit is robust with respect to alterations in prolactin signaling. In contrast, acute deletion of Prlr in all MPOA neurons of adult female mice resulted in profound deficits in maternal care soon after birth. All mothers abandoned their pups, showing that prolactin action on MPOA neurons is necessary for the normal expression of postpartum maternal behavior in mice. Our data establish a critical role for prolactin-induced behavioral responses in the maternal brain, ensuring survival of mammalian offspring.
- Published
- 2017
28. Lactation induces increases in the RANK/RANKL/OPG system in maxillary bone
- Author
-
George J. Dias, Soraia Macari, Tarcília Aparecida Silva, Lavanya Ajay Sharma, Amanda Wyatt, David R. Grattan, Janine Maíra da Silva, and Raphael E. Szawka
- Subjects
musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Osteoclasts ,Bone remodeling ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Osteoprotegerin ,Osteoclast ,Internal medicine ,medicine ,Maxilla ,Periodontal fiber ,Animals ,Lactation ,Dental alveolus ,Osteoblasts ,biology ,Receptor Activator of Nuclear Factor-kappa B ,business.industry ,RANK Ligand ,Osteoblast ,Cell Differentiation ,030206 dentistry ,X-Ray Microtomography ,medicine.disease ,Prolactin ,Osteopenia ,Mice, Inbred C57BL ,Bone Diseases, Metabolic ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Phenotype ,RANKL ,biology.protein ,Female ,Bone Remodeling ,business - Abstract
The underlying causes of maxillary bone loss during lactation remain poorly understood. We evaluated the impact of lactation on physiological and mechanically-induced alveolar bone remodeling. Nulliparous non-lactating (N-LAC) and 21-day lactating (LAC) mice underwent mechanically-induced bone remodeling by orthodontic tooth movement (OTM). Micro-computed tomography (microCT) was performed in the maxilla, femur and vertebra. Tartrate-resistant-acid phosphatase (TRAP) and Masson's trichrome labelling was performed in the maxillary bone and gene expression was determined in the periodontal ligament. The effect of prolactin on osteoclast (OCL) and osteoblast (OBL) differentiation was also investigated in N-LAC and LAC mice. Lactation increased alveolar bone loss in the maxilla, femur and vertebra, while OTM was enhanced. The number of OCL and OBL was higher in the maxilla of LAC mice. OTM increased OCL in both groups; while OBL was increased only in N-LAC but not in LAC mice, in which cell numbers were already elevated. The alveolar bone loss during lactation was associated with increased expression of receptor activator of nuclear factor-KappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in the maxilla. OTM induced the same responses in N-LAC mice, whereas it had no further effect in LAC mice. Lactation enhanced differentiation of OCL and OBL from bone marrow cells, and prolactin recapitulated OCL differentiation in N-LAC mice. Thus, lactation increases physiological maxillary bone remodeling and OTM, and both require activation of RANK/RANKL/OPG system. These findings expand our knowledge of lactation-induced osteopenia and have possible impact on clinical practice regarding orthodontic treatments and dental implants in lactating women.
- Published
- 2017
29. Conducting Actigraphy Research in Children With Neurodevelopmental Disorders—A Practical Approach
- Author
-
Beth A. Malow, Deborah D. Wofford, Diane B. Fawkes, Amanda Wyatt, Ann Reynolds, Alvin Loh, Karen W. Adkins, Shelly K. Weiss, and Suzanne E. Goldman
- Subjects
Male ,Parents ,medicine.medical_specialty ,Special populations ,Developmental Disabilities ,Neuroscience (miscellaneous) ,Medicine (miscellaneous) ,Article ,Humans ,Multicenter Studies as Topic ,Medicine ,Child ,Sleep Medicine Specialty ,Clinical Trials as Topic ,business.industry ,Pediatric research ,Actigraphy ,medicine.disease ,Clinical trial ,Caregivers ,Child Development Disorders, Pervasive ,Child, Preschool ,Parent training ,Physical therapy ,Autism ,Basic level ,Female ,Neurology (clinical) ,Psychology (miscellaneous) ,business - Abstract
The literature has been highly informative for when to use actigraphy and its validity in pediatric research. However, minimal literature exists on how to perform actigraphy, especially in special populations. We determined whether providing actigraphy training to parents and coordinators increased the nights of actigraphy data that could be scored. We compared two studies in children with autism spectrum disorders, one of which provided a basic level of training in a single-site trial and the other of which provided more detailed training to parents and coordinators in a multisite trial. There was an increase in scorable nights in the multisite trial containing a one-hour structured parent training session. Our results support the use of educational tools in clinical trials that use actigraphy.
- Published
- 2014
30. Solving a Neurologic Mystery: Recognizing Rheumatic Fever in the Pediatric Patient
- Author
-
Lori Thompson, Amanda Wyatt, and Jerithea Tidwell
- Subjects
Pediatrics ,medicine.medical_specialty ,Weakness ,Pathology ,Referral ,business.industry ,Mood swing ,Sydenham's chorea ,Emergency department ,medicine.disease ,Nervous System ,Psychological evaluation ,Diagnosis, Differential ,Pediatric patient ,Pediatrics, Perinatology and Child Health ,medicine ,Humans ,Rheumatic fever ,Female ,Rheumatic Fever ,medicine.symptom ,Child ,business ,Physical Examination - Abstract
HISTORY OF PRESENT ILLNESS The mother reported that her child has been fatigued during the past month and sleeping more than usual. The child had been healthy until about two weeks ago when the mother noticed uncontrollable twitching, mood swings, and agitation. The uncontrollable body movements became progressively worse and were more prominent on the left side. Two days ago the child s speech became slurred and it sounded as though ‘‘her tongue was too big for her mouth.’’ The child was seen in an emergency department, and her laboratory tests and head computed tomography scan were normal. She was diagnosed as having a psychiatric disorder and released with instructions to follow up with her primary care provider, with no referral for a psychiatric evaluation. Today she began having left-sided weakness as well as unsteadiness on her feet.
- Published
- 2011
31. Analysis of prolactin receptor expression in the murine brain using a novel prolactin receptor reporter mouse
- Author
-
David R. Grattan, Hollian R Phillipps, Fabien Ectors, Ilona C. Kokay, Ulrich Boehm, Amanda Wyatt, and Mari Aoki
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Receptors, Prolactin ,Endocrinology, Diabetes and Metabolism ,Central nervous system ,Cre recombinase ,Mice, Transgenic ,Biology ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Endocrinology ,Genes, Reporter ,Internal medicine ,medicine ,Animals ,Neurons ,Endocrine and Autonomic Systems ,Prolactin receptor ,Brain ,Prolactin ,Cell biology ,Stria terminalis ,030104 developmental biology ,medicine.anatomical_structure ,Female ,Brainstem ,Anteroventral periventricular nucleus ,Nucleus ,030217 neurology & neurosurgery - Abstract
Prolactin influences a wide range of physiological functions via actions within the central nervous system, as well as in peripheral tissues. A significant limitation in studies investigating these functions is the difficulty in identifying prolactin receptor (Prlr) expression, particularly in the brain. We have developed a novel mouse line using homologous recombination within mouse embryonic stem cells to produce a mouse in which an internal ribosome entry site (IRES) followed by Cre recombinase cDNA is inserted immediately after exon 10 in the Prlr gene, thereby targeting the long isoform of the Prlr. By crossing this Prlr-IRES-Cre mouse with a ROSA26-CAGS-tauGFP (τGFP) reporter mouse line, and using immunohistochemistry to detect τGFP, we were able to generate a detailed map of the distribution of individual Prlr-expressing neurones and fibres throughout the brain of adult mice without the need for amplification of the GFP signal. Because the τGFP is targeted to neurotubules, the labelling detected not only cell bodies, but also processes of prolactin-sensitive neurones. In both males and females, Cre-dependent τGFP expression was localised, with varying degrees of abundance, in a number of brain regions, including the lateral septal nucleus, bed nucleus of the stria terminalis, preoptic and hypothalamic nuclei, medial habenula, posterodorsal medial amygdala, and brainstem regions such as the periaqueductal grey and parabrachial nucleus. The labelling was highly specific, occurring only in cells where we could also detect PrlrmRNA by in situ hybridisation. Apart from two brain areas, the anteroventral periventricular nucleus and the medial preoptic nucleus, the number and distribution of τGFP-immunopositive cells was similar in males and females, suggesting that prolactin may have many equivalent functions in both sexes. These mice provide a valuable tool for investigating the neural circuits underlying the actions of prolactin.
- Published
- 2018
32. Bitter taste cells in the ventricular walls of the murine brain regulate glucose homeostasis
- Author
-
Qiang Yu, Igor Gamayun, Philipp Wartenberg, Qian Zhang, Sen Qiao, Soumya Kusumakshi, Sarah Candlish, Viktoria Götz, Shuping Wen, Debajyoti Das, Amanda Wyatt, Vanessa Wahl, Fabien Ectors, Kathrin Kattler, Daniela Yildiz, Vincent Prevot, Markus Schwaninger, Gaetan Ternier, Paolo Giacobini, Philippe Ciofi, Timo D. Müller, and Ulrich Boehm
- Subjects
Multidisciplinary ,Physiology ,FOS: Biological sciences ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology ,Neuroscience - Abstract
The median eminence (ME) is a circumventricular organ at the base of the brain that controls body homeostasis. Tanycytes are its specialized glial cells that constitute the ventricular walls and regulate different physiological states, however individual signaling pathways in these cells are incompletely understood. Here, we identify a functional tanycyte subpopulation that expresses key taste transduction genes including bitter taste receptors, the G protein gustducin and the gustatory ion channel TRPM5 (M5). M5 tanycytes have access to blood-borne cues via processes extended towards diaphragmed endothelial fenestrations in the ME and mediate bidirectional communication between the cerebrospinal fluid and blood. This subpopulation responds to metabolic signals including leptin and other hormonal cues and is transcriptionally reprogrammed upon fasting. Acute M5 tanycyte activation induces insulin secretion and acute diphtheria toxin-mediated M5 tanycyte depletion results in impaired glucose tolerance in diet-induced obese mice. We provide a cellular and molecular framework that defines how bitter taste cells in the ME integrate chemosensation with metabolism.
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.