20 results on '"Kirste, Imke"'
Search Results
2. Early breast development in overweight girls: does estrogen made by adipose tissue play a role?
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Carlson, Lauren, Flores Poccia, Vanessa, Sun, Bob Z., Mosley, Brittany, Kirste, Imke, Rice, Annette, Sridhar, Rithi, Kangarloo, Tairmae, Vesper, Hubert W., Duke, Lumi, Botelho, Julianne C, Filie, Armando C, Adams, Judy M, and Shaw, Natalie D.
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- 2019
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3. Abstract 16486: Tlr3 is Necessary for Direct Cardiac Reprogramming
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Hodgkinson, Conrad, Pratt, Richard, Kirste, Imke, Cooke, John, and Dzau, Victor
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- 2017
4. Emergence of Individuality in Genetically Identical Mice
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Freund, Julia, Brandmaier, Andreas M., Lewejohann, Lars, Kirste, Imke, Kritzler, Mareike, Krüger, Antonio, Sachser, Norbert, Lindenberger, Ulman, and Kempermann, Gerd
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- 2013
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5. Is silence golden? Effects of auditory stimuli and their absence on adult hippocampal neurogenesis
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Kirste, Imke, Nicola, Zeina, Kronenberg, Golo, Walker, Tara L., Liu, Robert C., and Kempermann, Gerd
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- 2015
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6. Repetitive magnetic stimulation of human-derived neuron-like cells activates cAMP-CREB pathway
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Hellmann, Julian, Jüttner, Rene, Roth, Clarisse, Bajbouj, Malek, Kirste, Imke, Heuser, Isabella, Gertz, Karen, Endres, Matthias, and Kronenberg, Golo
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- 2012
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7. Reduced hippocampal neurogenesis in the GR+/− genetic mouse model of depression
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Kronenberg, Golo, Kirste, Imke, Inta, Dragos, Chourbaji, Sabine, Heuser, Isabella, Endres, Matthias, and Gass, Peter
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- 2009
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8. Quantitative modeling of the dynamics of adult hippocampal neurogenesis in mice
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Bandt Christoph, Kirste Imke, Lezius Susanne, Kempermann Gerd, and Wiskott Laurenz
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurophysiology and neuropsychology ,QP351-495 - Published
- 2009
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9. Clinical Utility of Elecsys Anti-SARS-CoV-2 S Assay in COVID-19 Vaccination: An Exploratory Analysis of the mRNA-1273 Phase 1 Trial.
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Jochum, Simon, Kirste, Imke, Hortsch, Sayuri, Grunert, Veit Peter, Legault, Holly, Eichenlaub, Udo, Kashlan, Basel, and Pajon, Rolando
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COVID-19 vaccines ,NEUTRALIZATION tests ,ANTIBODY formation ,HUMORAL immunity - Abstract
Background: The ability to quantify an immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential. This study assessed the clinical utility of the quantitative Roche Elecsys
® Anti-SARS-CoV-2 S assay (ACOV2S) using samples from the 2019-nCoV vaccine (mRNA-1273) phase 1 trial (NCT04283461). Methods: Samples from 30 healthy participants, aged 18–55 years, who received two injections with mRNA-1273 at a dose of 25 μg (n=15) or 100 μg (n=15), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results (shown in U/mL – equivalent to BAU/mL per the first WHO international standard) were compared with results from ELISAs specific to antibodies against the Spike protein (S-2P) and the receptor binding domain (RBD) as well as neutralization tests including nanoluciferase (nLUC80), live-virus (PRNT80), and a pseudovirus neutralizing antibody assay (PsVNA50). Results: RBD-specific antibodies were already detectable by ACOV2S at the first time point of assessment (d15 after first vaccination), with seroconversion before in all but two participants (25 μg dose group); all had seroconverted by Day 29. Across all post-baseline visits, geometric mean concentration of antibody levels was 3.27–7.48-fold higher in the 100 μg compared with the 25 μg dose group. ACOV2S measurements were highly correlated with those from RBD ELISA (Pearson's r=0.938; p<0.0001) and S-2P ELISA (r=0.918; p<0.0001). For both ELISAs, heterogeneous baseline results and smaller increases in antibody levels following the second vs first vaccination compared with ACOV2S were observed. ACOV2S showed absence of any baseline noise indicating high specificity detecting vaccine-induced antibody response. Moderate–strong correlations were observed between ACOV2S and neutralization tests (nLUC80 r=0.933; PsVNA50, r=0.771; PRNT80, r=0.672; all p ≤ 0.0001). Conclusion: The Elecsys Anti-SARS-CoV-2 S assay (ACOV2S) can be regarded as a highly valuable method to assess and quantify the presence of RBD-directed antibodies against SARS-CoV-2 following vaccination and may indicate the presence of neutralizing antibodies. As a fully automated and standardized method, ACOV2S could qualify as the method of choice for consistent quantification of vaccine-induced humoral response. [ABSTRACT FROM AUTHOR]- Published
- 2022
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10. Psychosocial influences on the dynamics of adult hippocampal neurogenesis
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Kirste, Imke
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500 Naturwissenschaften und Mathematik::570 Biowissenschaften ,Biologie ,proliferation ,social, behavior ,depression ,differentiation - Abstract
The term “adult neurogenesis” describes the continuous generation of cohorts of new neurons in some discrete regions of the adult brain, such as the dentate gyrus of the hippocampus. Adult hippocampal neurogenesis (ahNG) has been shown as relevant for typical functions of this brain areal (e.g. memory consolidation), but also influences social behavior and has medical relevance. The exact dynamics of this neuronal development are still unknown, as are psychosocial impacts on this process. To analyze the temporal pattern of ahNG and quantify the development of the new neurons we analyzed the relative and absolute numbers of cells in all known stages of the neural differentiation, from stem cell phase towards neurons, in mice at different time points after BrdU injection. BrdU permanently labels cells during S-phase of the cell cycle and enabled us to follow a cohort of new cells over time, thus, here a pseudo- longitudinal study was performed. Subsequently, first studies on the relation between social factors and ahNG in mammals are presented. Regulation of the neuronal development is related to, and dependent on inputs from the outer environment. A connection between ahNG and social environment has been demonstrated previously, but detailed information on the altered differentiation process is missing. In the first part of this thesis I present detailed information on the progression of distinct cell types through the differentiation process of ahNG. Transitions over time are observed allowing the estimation of cell cycle length (CCL) for each cell type involved in ahNG. I found, that the individual cell types are more flexible than assumed before. In the second part, I investigate the impact of social housing, (behavioral relevant) auditori stimuli and stress on ahNG. While the positive factors were applied to healthy subjects, I used the stress paradigm in the GR+/- mice model of depression. Flexible adaptations of different stages in ahNG were also found in these studies on social factors. Each single stimulator affected individual differentiation stages in characteristic ways. While group size, music, silence and pup calls increase BrdU cell counts in proliferation analyses, with distinct effects on each mitotic differentiation stage, does only silence increase survival of new neurons. In the GR+/- mouse model I found decreased ahNG, without any effect on the proportion of neurogenesis or gliogenesis. Based on the information obtained about the dynamics of ahNG a new, innovative model of ahNG is proposed, pushing type-1 and type-2a cells in the center of attention, while diminishing the weight of type-3 cells for the process of differentiation. Type-1 cells, previously assumed as origin of neurogenesis in the hippocampus, are here hypothesized as safeguard of the system, while type-2a cells, highly proliferative, giving rise to gliogenesis and neurogenesis, are hypothesized as the origin of ahNG under normal, healthy conditions. The additional studies give some indications for changes of the model caused by different social factors. The aim is to draw attention to the importance and impact of social environment on adult neurogenesis, brain plasticity and mental health. Thus, future studies will focus more on the promising field of ahNG., Der Begriff “Adulte Neurogenese” beschreibt die kontinuierliche Generierung neuer Nervenzellen in bestimmten Arealen des erwachsenen Gehirns, wie zum Beispiel dem Hippocampus. Adulte hippocampale Neurogenese (ahNG) ist im Säugetier stark in regional spezifische Funktionen, wie z.B. dem semantischen Gedächtnis, involviert, kann aber auch soziales Verhalten beeinflussen und besitzt zusätzlich medizinische Relevanz. Der exakte Ablauf der neuronalen Entwicklung im Gyrus Dentatus ist bislang ungewiss und soziale Einflüsse auf diesen Prozess wurden noch wenig untersucht. Um den zeitlichen Verlauf der adulten, hippokampalen Neurogenese zu analysieren und die Generierung neuer Körnerzellen zu quantifizieren, wurden als erstes sowohl relative als auch absolute Werte einzelner Entwicklungsstadien zu verschiedenen Zeitpunkten nach BrdU Administration erhoben. BrdU markiert dabei Zellen in der S-Phase des Zellzyklus und ermöglicht es, einer Kohorte neuer Zellen über einen festgelegten Zeitraum zu folgen. Somit handelt es sich bei diesem Teil der Dissertation um eine Pseudo-longitudinale Studie. Im Anschluss werden erstmals Studien präsentiert, welche den Zusammenhang zwischen ahNG und sozialen Faktoren, wie Gruppenzusammensetzung und (z.T. verhaltensrelevanten) auditiven Stimulationen, in gesunden Mäusen untersuchen und dabei vor allem Bezug auf die verschiedenen Differenzierungsstadien nehmen. Neben Untersuchungen im gesunden Organismus wurde zusätzlich der Effekt von Stress in Mäusen mit reduzierter Expression des Glucocorticoid-Rezeptors erforscht. Dieser Mausstamm stellt ein anerkanntes Depressionsmodel dar, mit für Depression typischen, sozialen Verhaltenswesen. Die Ergebnisse zur Dynamik der ahNG zeigen starke Unterschiede zwischen den Zelltypen der einzelnen Differenzierungsstadien, insbesondere bezüglich der Proliferationsrate und der Zellzykluslänge (CCL). Interessanterweise sind die Unterschiede zwischen den einzelnen Zellstadien noch größer als bisher angenommen, e.g. in Bezug auf den Zellzyklus). Flexible Anpassungen an den Zeitverlauf der ahNG werden auch im Falle sozialer Stimulation aufgezeigt. Während steigende Gruppengröße, Musik, Stille und Rufe isolierter Säuglinge, die Anzahl BrdU-positiver Zellen in Proliferationsanalysen erhöhte, zeigte nur Stille eine Steigerung der Neurogenese in Bezug auf Überlebensraten neugebildeter Nervenzellen. In unserem GR+/- Depressionsmodel fanden wir eine Reduktion der ahNG, ohne Beeinflussung der Neurogenese- oder Gliogenese-Rate. Basierend auf den Ergebnissen zur Dynamic der ahNG wird ein neues Modell der ahNG vorgestellt, dass erstmalig nicht nur Type-1 Zellen als den bisher vermuteten Ursprung der Neurogenese, sondern auch Type-2a Zellen in das Zentrum stellt. Hingegen wird die Bedeutung der Type-3 Zellen zugunsten von Type-2b und unreifen Körnerzellen gemindert. Type-1 Zellen werden hier als Sicherung des Systems propagiert, während stark proliferierende Type-2a Zellen sowohl Gliogenese als auch Neurogenese begründen. Eine hohe Flexibilität zeichnet das System der Neubildung neuer Nervenzellen aus, wie wir auch mit den Ergebnissen der anderen Studien zeigen konnten. Die weiteren Studien lassen vermuten, dass die Dynamik der ahNG, wie im Model dargestellt, durch soziale Faktoren verändert werden kann. Diese Untersuchungen sollen Interesse an einem zukünftigen Forschungsfeld wecken, dessen Zweck es sein wird den Zusammenhang zwischen sozialen Umwelteinflüssen, hippokampaler Neurogenese, Gehirnplastizität und mentaler Gesundheit zu lenken.
- Published
- 2012
11. Demethylation of H3K27 Is Essential for the Induction of Direct Cardiac Reprogramming by miR Combo.
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Dal-Pra, Sophie, Hodgkinson, Conrad P., Mirotsou, Maria, Kirste, Imke, and Dzau, Victor J.
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- 2017
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12. Impact of Actin Filament Stabilization on Adult Hippocampal and Olfactory Bulb Neurogenesis.
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Kronenberg, Golo, Gertz, Karen, Baldinger, Tina, Kirste, Imke, Eckart, Sarah, Yildirim, Ferah, Shengbo Ji, Heuser, Isabella, Schröck, Helmut, Hörtnagl, Heide, Sohr, Reinhard, Djoufack, Pierre Chryso, Jüttner, René, Glass, Rainer, Przesdzing, Ingo, Kumar, Jitender, Freyer, Dorette, Hellweg, Rainer, Kettenmann, Helmut, and Fink, Klaus Benno
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ACTIN ,HIPPOCAMPUS (Brain) ,OLFACTORY cortex ,DEVELOPMENTAL neurobiology ,NITRIC oxide ,ANIMAL models in research - Abstract
Rearrangement of the actin cytoskeleton is essential for dynamic cellular processes. Decreased actin turnover and rigidity of cytoskeletal structures have been associated with aging and cell death. Gelsolin is a Ca
2+ -activated actin-severing protein that is widely expressed throughout the adult mammalian brain. Here, we used gelsolin-deficient (Gsn-/- ) mice as a model system for actin filament stabilization. In Gsn-/- mice, emigration of newly generated cells from the subventricular zone into the olfactory bulb was slowed. In vitro, gelsolin deficiency did not affect proliferation or neuronal differentiation of adult neural progenitors cells (NPCs) but resulted in retarded migration. Surprisingly, hippocampal neurogenesis was robustly induced by gelsolin deficiency. The ability of NPCs to intrinsically sense excitatory activity and thereby implement coupling between network activity and neurogenesis has recently been established. Depolarization-induced [Ca2+ ]i increases and exocytotic neurotransmitter release were enhanced in Gsn-/- synaptosomes. Importantly, treatment of Gsn-/- synaptosomes with mycotoxin cytochalasin D, which, like gelsolin, produces actin disassembly, decreased enhanced Ca2+ influx and subsequent exocytotic norepinephrine release to wild-type levels. Similarly, depolarization-induced glutamate release from Gsn-/- brain slices was increased. Furthermore, increased hippocampal neurogenesis in Gsn-/- mice was associated with a special microenvironment characterized by enhanced density of perfused vessels, increased regional cerebral blood flow, and increased endothelial nitric oxide synthase (NOS-III) expression in hippocampus. Together, reduced filamentous actin turnover in presynaptic terminals causes increased Ca2+ influx and, subsequently, elevated exocytotic neurotransmitter release acting on neural progenitors. Increased neurogenesis in Gsn-/- hippocampus is associated with a special vascular niche for neurogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2010
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13. Reduced hippocampal neurogenesis in the GR+/− genetic mouse model of depression.
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Kronenberg, Golo, Kirste, Imke, Inta, Dragos, Chourbaji, Sabine, Heuser, Isabella, Endres, Matthias, and Gass, Peter
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HIPPOCAMPUS (Brain) , *DEVELOPMENTAL neurobiology , *GLUCOCORTICOID receptors , *MENTAL depression , *AFFECTIVE disorders - Abstract
Glucocorticoid receptor (GR) heterozygous mice (GR+/ −) represent a valuable animal model for major depression. GR+/ − mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR+/ − animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied here the effects of the GR+/ − genotype on neurogenesis in vivo. In a 2 × 2 design, GR+/ − mice and GR+/+ littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks later. BrdU cell counts were significantly reduced as an effect of GR+/ − genotype and as an effect of stress. Majority of the BrdU+ cells showed co-labeling with mature neuronal marker NeuN or astrocytic marker S100β with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced neurogenesis in GR+/ − mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis, stress, neurotrophins, and behavioral symptoms of and susceptibility to depression. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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14. Maintenance and Representation of Mind Wandering during Resting-State fMRI.
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Chou, Ying-hui, Sundman, Mark, Whitson, Heather E., Gaur, Pooja, Chu, Mei-Lan, Weingarten, Carol P., Madden, David J., Wang, Lihong, Kirste, Imke, Joliot, Marc, Diaz, Michele T., Li, Yi-Ju, Song, Allen W., and Chen, Nan-kuei
- Abstract
Major advances in resting-state functional magnetic resonance imaging (fMRI) techniques in the last two decades have provided a tool to better understand the functional organization of the brain both in health and illness. Despite such developments, characterizing regulation and cerebral representation of mind wandering, which occurs unavoidably during resting-state fMRI scans and may induce variability of the acquired data, remains a work in progress. Here, we demonstrate that a decrease or decoupling in functional connectivity involving the caudate nucleus, insula, medial prefrontal cortex and other domain-specific regions was associated with more sustained mind wandering in particular thought domains during resting-state fMRI. Importantly, our findings suggest that temporal and between-subject variations in functional connectivity of above-mentioned regions might be linked with the continuity of mind wandering. Our study not only provides a preliminary framework for characterizing the maintenance and cerebral representation of different types of mind wandering, but also highlights the importance of taking mind wandering into consideration when studying brain organization with resting-state fMRI in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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15. Quantitative modeling of the dynamics of adult hippocampal neurogenesis in mice.
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Lezius, Susanne, Kirste, Imke, Bandt, Christoph, Kempermann, Gerd, and Wiskott, Laurenz
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BIOLOGICAL mathematical modeling , *MOLECULAR dynamics , *DEVELOPMENTAL neurobiology , *HIPPOCAMPUS (Brain) , *LABORATORY mice - Abstract
The hippocampus is special in that it generates new neurons throughout life. This development of new granule cells in the adult dentate gyrus is referred to as adult hippocampal neurogenesis. A kinetic model of this development has been established. Therein the process of neurogenesis is composed of a sequence of different cell types. However, the exact dynamics of neuronal development in the dentate gyrus are unknown. To quantify the development we collected time-series like data. By injections of BrdU, the dividing cells were labeled and cell numbers could be counted at different time points after injection (2 h to 21 d). We determined relative numbers of BrdU-positive cells of the respective types. These numbers allow us to monitor the development of a labeled cell cohort through the different cell types over the analyzed time period. We also determined absolute cell numbers of different unlabeled populations. They do not show a time dependence, which leads to the idea of a dynamic equilibrium of cells of the different cell types on the analyzed timescale. Based on the known properties of the process and a prior model we established a detailed mathematical model containing the different developmental stages. Here we used the idea of the Leslie matrix, which is a discrete and age-structured model of population growth. The transition probabilities were found by fitting the parameters of the model to the data. We also included a simulated labeling process by which the initial cell populations are determined in a self-consistent manner based on the transition probabilities of the model. Furthermore, the effect of label dilution is included by applying a sigmoidal detectability function. The results of the model match well the data (see figure 1). The model enables us to deduce rates for division and death of cells of the different cell types as well as properties of the labeling process. Finally, based on the eigenvectors of the transition matrix we derive an estimate for the population of unlabeled cells, which matches the experimental data well without being fitted to them. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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16. Reduced Hippocampal Neurogenesis in Mice Deficient in Apoptosis Repressor with Caspase Recruitment Domain (ARC).
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Kronenberg, Golo, Gertz, Karen, Uhlemann, Ria, Kuffner, Melanie T.C., Kirste, Imke, An, Junfeng, Jadavji, Nafisa M., Schott, Bjoern H., Scheffel, Thomas, Endres, Matthias, Hellweg, Rainer, and Harms, Christoph
- Subjects
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GRANULE cells , *NEURAL stem cells , *BRAIN-derived neurotrophic factor , *DEVELOPMENTAL neurobiology , *CELL death , *DENTATE gyrus - Abstract
In the adult hippocampal dentate gyrus (DG), the majority of newly generated cells are eliminated by apoptotic mechanisms. The apoptosis repressor with caspase recruitment domain (ARC), encoded by the Nol3 gene, is a potent and multifunctional death repressor that inhibits both death receptor and mitochondrial apoptotic signaling. The aim of the present study was to parse the role of ARC in the development of new granule cell neurons. Nol3 gene expression as revealed by in situ hybridization is present in the entire dentate granule cell layer. Moreover, a comparison of Nol3 expression between FACS-sorted Sox2-positive neural stem cells and Doublecortin (DCX)-positive immature neurons demonstrates upregulation of Nol3 during neurogenesis. Using ARC-deficient mice, we show that proliferation and survival of BrdU birth-dated cells are strongly reduced in the absence of ARC while neuronal-glial fate choice is not affected. Both the number of DCX-positive cells and the number of calretinin (CR)-positive immature postmitotic neurons are reduced in the hippocampus of ARC−/− mice. ARC knockout is not associated with increased numbers of microglia or with microglia activation. However, hippocampal brain-derived neurotrophic factor (BDNF) protein content is significantly increased in ARC−/− mice, possibly representing a compensatory response. Collectively, our results suggest that ARC plays a critical cell-autonomous role in preventing cell death during adult granule cell neogenesis. • Reduced net hippocampal neurogenesis in ARC−/− mice • ARC knockout not associated with increased microglia density or activation • Increased BDNF concentrations in microdissected left hippocampus of ARC−/− mice [ABSTRACT FROM AUTHOR]
- Published
- 2019
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17. Task difficulty modulates brain activation in the emotional oddball task.
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Siciliano, Rachel E., Madden, David J., Tallman, Catherine W., Boylan, Maria A., Kirste, Imke, Monge, Zachary A., Packard, Lauren E., Potter, Guy G., and Wang, Lihong
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BRAIN physiology , *COGNITIVE ability , *FUNCTIONAL magnetic resonance imaging , *EMOTIONS , *TASK performance - Abstract
Previous functional magnetic resonance imaging (fMRI) studies have reported that task-irrelevant, emotionally salient events can disrupt target discrimination, particularly when attentional demands are low, while others demonstrate alterations in the distracting effects of emotion in behavior and neural activation in the context of attention-demanding tasks. We used fMRI, in conjunction with an emotional oddball task, at different levels of target discrimination difficulty, to investigate the effects of emotional distractors on the detection of subsequent targets. In addition, we distinguished different behavioral components of target detection representing decisional, nondecisional, and response criterion processes. Results indicated that increasing target discrimination difficulty led to increased time required for both the decisional and nondecisional components of the detection response, as well as to increased target-related neural activation in frontoparietal regions. The emotional distractors were associated with activation in ventral occipital and frontal regions and dorsal frontal regions, but this activation was attenuated with increased difficulty. Emotional distraction did not alter the behavioral measures of target detection, but did lead to increased target-related frontoparietal activation for targets following emotional images as compared to those following neutral images. This latter effect varied with target discrimination difficulty, with an increased influence of the emotional distractors on subsequent target-related frontoparietal activation in the more difficult discrimination condition. This influence of emotional distraction was in addition associated specifically with the decisional component of target detection. These findings indicate that emotion-cognition interactions, in the emotional oddball task, vary depending on the difficulty of the target discrimination and the associated limitations on processing resources. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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18. Exofocal Dopaminergic Degeneration as Antidepressant Target in Mouse Model of Poststroke Depression
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Kronenberg, Golo, Balkaya, Mustafa, Prinz, Vincent, Gertz, Karen, Ji, Shengbo, Kirste, Imke, Heuser, Isabella, Kampmann, Björn, Hellmann-Regen, Julian, Gass, Peter, Sohr, Reinhard, Hellweg, Rainer, Waeber, Christian, Juckel, Georg, Hörtnagl, Heide, Stumm, Ralf, and Endres, Matthias
- Subjects
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DOPAMINERGIC mechanisms , *NEURODEGENERATION , *ANTIDEPRESSANTS , *MENTAL depression , *DYNORPHINS , *AUTORADIOGRAPHY , *LABORATORY mice - Abstract
Background: Although poststroke depression (PSD) is a frequent chronic complication of stroke with high relevance for outcome and survival, underlying pathomechanisms remain inadequately understood. This may be because suitable animal models are largely lacking and existing models are poorly characterized. Methods: Male 129/SV mice were subjected to 30-min middle cerebral artery occlusion (MCAo)/reperfusion and serial magnetic resonance imaging scans. A subset of animals received selective serotonin reuptake inhibitor citalopram starting 7 days after MCAo. Behavioral assessment was performed at 14 weeks. To identify biological correlates of PSD, we quantified corticosterone levels in serum and brain-derived neurotrophic factor levels in brain. The integrity of the mesolimbic dopaminergic system was assessed using tyrosine hydroxylase and dynorphin in situ hybridizations as well as dopamine transporter autoradiography. Results: Left, but not right, MCAo, elicited anhedonia and increased anxiety and despair. This depression-like syndrome was associated with alterations in the mesolimbic reward system. MCAo resulted in delayed degeneration of dopaminergic neurons in ipsilateral midbrain, which was accompanied by reduced dopamine concentrations and decreased levels of dopamine transporter density along with increased brain-derived neurotrophic factor protein levels in ischemic striatum and increased dynorphin messenger RNA expression in nucleus accumbens. Chronic antidepressant treatment initiated as late as 7 days after stroke reversed the behavioral phenotype, prevented degeneration of dopaminergic midbrain neurons, and attenuated striatal atrophy at 4 months. Conclusions: Our results highlight the importance of the dopaminergic system for the development of PSD. Prevention of secondary neurodegeneration by antidepressants may provide a novel target for subacute stroke therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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19. Clinical utility of Elecsys Anti-SARS-CoV-2 S assay in COVID-19 vaccination: An exploratory analysis of the mRNA-1273 phase 1 trial.
- Author
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Jochum S, Kirste I, Hortsch S, Grunert VP, Legault H, Eichenlaub U, Kashlan B, and Pajon R
- Abstract
Background: The ability to quantify an immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential. This study assessed the clinical utility of the quantitative Roche Elecsys
® Anti-SARS-CoV-2 S assay (ACOV2S) using samples from the 2019-nCoV vaccine (mRNA-1273) phase 1 trial (NCT04283461)., Methods: Samples from 30 healthy participants, aged 18-55 years, who received two injections with mRNA-1273 at a dose of 25 μg (n=15) or 100 μg (n=15), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results (shown in U/mL - equivalent to BAU/mL per the first WHO international standard) were compared with results from ELISAs specific to antibodies against the Spike protein (S-2P) and the receptor binding domain (RBD) as well as neutralization tests including nanoluciferase (nLUC80 ), live-virus (PRNT80 ), and a pseudovirus neutralizing antibody assay (PsVNA50 )., Results: RBD-specific antibodies were already detectable by ACOV2S at the first time point of assessment (d15 after first vaccination), with seroconversion before in all but 2 participants (25 μg dose group); all had seroconverted by Day 29. Across all post-baseline visits, geometric mean concentration of antibody levels were 3.27-7.48-fold higher in the 100 μg compared with the 25 μg dose group. ACOV2S measurements were highly correlated with those from RBD ELISA (Pearson's r=0.938; p<0.0001) and S-2P ELISA (r=0.918; p<0.0001). For both ELISAs, heterogeneous baseline results and smaller increases in antibody levels following the second vs first vaccination compared with ACOV2S were observed. ACOV2S showed absence of any baseline noise indicating high specificity detecting vaccine-induced antibody response. Moderate-strong correlations were observed between ACOV2S and neutralization tests (nLUC80 r=0.933; PsVNA50 , r=0.771; PRNT80 , r=0.672; all p≤0.0001)., Conclusion: The Elecsys Anti-SARS-CoV-2 S assay (ACOV2S) can be regarded as a highly valuable method to assess and quantify the presence of RBD-directed antibodies against SARS-CoV-2 following vaccination, and may indicate the presence of neutralizing antibodies. As a fully automated and standardized method, ACOV2S could qualify as the method of choice for consistent quantification of vaccine-induced humoral response., Competing Interests: Competing interests Simon Jochum, Imke Kirste, Sayuri Hortsch, Veit Peter Grunert and Udo Eichenlaub are employees of Roche Diagnostics. Basel Kashlan is an employee of PPD, Inc. Holly Legault and Rolando Pajon are employees of Moderna, Inc.- Published
- 2021
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20. Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B.
- Author
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Hodgkinson CP, Pratt RE, Kirste I, Dal-Pra S, Cooke JP, and Dzau VJ
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- Animals, Animals, Newborn, Cellular Reprogramming, Fibroblasts cytology, Fibroblasts metabolism, Gene Expression Regulation, Mice, Inbred C57BL, MicroRNAs genetics, MicroRNAs metabolism, Promoter Regions, Genetic genetics, Protein Subunits metabolism, Toll-Like Receptor 3 antagonists & inhibitors, Transcription Factor RelA metabolism, Cell Differentiation, Myocytes, Cardiac cytology, Myocytes, Cardiac metabolism, NF-kappa B metabolism, Toll-Like Receptor 3 metabolism
- Abstract
The process by which committed precursors mature into cardiomyocytes is poorly understood. We found that TLR3 inhibition blocked cardiomyocyte maturation; precursor cells committed to the cardiomyocyte lineage failed to express maturation genes and sarcomeres did not develop. Using various approaches, we found that the effects of TLR3 upon cardiomyocyte maturation were dependent upon the RelA subunit of nuclear factor kappa B (NFκB). Importantly, under conditions that promote the development of mature cardiomyocytes NFκB became significantly enriched at the promoters of cardiomyocyte maturation genes. Furthermore, activation of the TLR3-NFκB pathway enhanced cardiomyocyte maturation. This study, therefore, demonstrates that the TLR3-NFκB pathway is necessary for the maturation of committed precursors into mature cardiomyocytes. Stem Cells 2018;36:1198-1209., (© AlphaMed Press 2018.)
- Published
- 2018
- Full Text
- View/download PDF
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