T-type Ca2+ channels, generating low threshold calcium influx in neurons, play a crucial role in the function of neuronal networks and their plasticity. To further investigate their role in the complex field of research in plasticity of... more
T-type Ca2+ channels, generating low threshold calcium influx in neurons, play a crucial role in the function of neuronal networks and their plasticity. To further investigate their role in the complex field of research in plasticity of neurons on a molecular level, this study aimed to analyse the impact of the vascular endothelial growth factor (VEGF) on these channels. VEGF, known as a player in vasculogenesis, also shows potent influence in the central nervous system, where it elicits neuronal growth. To investigate the influence of VEGF on the three T-type Ca2+ channel isoforms, Cav3.1 (encoded by Cacna1g), Cav3.2 (encoded by Cacna1h), and Cav3.3 (encoded by Cacna1i), lasermicrodissection of in vivo-grown Purkinje cells (PCs) was performed, gene expression was analysed via qPCR and compared to in vitro-grown PCs. We investigated the VEGF receptor composition of in vivo- and in vitro-grown PCs and underlined the importance of VEGF receptor 2 for PCs. Furthermore, we performed imm...
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Amyotrophic lateral sclerosis (ALS) is a progredient neurodegenerative disease characterized by a degeneration of the first and second motor neurons. Elevated levels of reactive oxygen species (ROS) and decreased levels of glutathione,... more
Amyotrophic lateral sclerosis (ALS) is a progredient neurodegenerative disease characterized by a degeneration of the first and second motor neurons. Elevated levels of reactive oxygen species (ROS) and decreased levels of glutathione, which are important defense mechanisms against ROS, have been reported in the central nervous system (CNS) of ALS patients and animal models. The aim of this study was to determine the cause of decreased glutathione levels in the CNS of the ALS model wobbler mouse. We analyzed changes in glutathione metabolism in the spinal cord, hippocampus, cerebellum, liver, and blood samples of the ALS model, wobbler mouse, using qPCR, Western Blot, HPLC, and fluorometric assays. Here, we show for the first time a decreased expression of enzymes involved in glutathione synthesis in the cervical spinal cord of wobbler mice. We provide evidence for a deficient glutathione metabolism, which is not restricted to the nervous system, but can be seen in various tissues o...
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The enteric nervous system (ENS) is an intrinsic network of neuronal ganglia in the intestinal tube with about 100 million neurons located in the myenteric plexus and submucosal plexus. These neurons being affected in neurodegenerative... more
The enteric nervous system (ENS) is an intrinsic network of neuronal ganglia in the intestinal tube with about 100 million neurons located in the myenteric plexus and submucosal plexus. These neurons being affected in neurodegenerative diseases, such as Parkinson’s disease, before pathological changes in the central nervous system (CNS) become detectable is currently a subject of discussion. Understanding how to protect these neurons is, therefore, particularly important. Since it has already been shown that the neurosteroid progesterone mediates neuroprotective effects in the CNS and PNS, it is now equally important to see whether progesterone has similar effects in the ENS. For this purpose, the RT-qPCR analyses of laser microdissected ENS neurons were performed, showing for the first time the expression of the different progesterone receptors (PR-A/B; mPRa, mPRb, PGRMC1) in rats at different developmental stages. This was also confirmed in ENS ganglia using immunofluorescence tec...
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Amyotrophic lateral sclerosis (ALS) is one of the most common incurable motor neuron disorders in adults. The majority of all ALS cases occur sporadically (sALS). Symptoms of ALS are caused by a progressive degeneration of motor neurons... more
Amyotrophic lateral sclerosis (ALS) is one of the most common incurable motor neuron disorders in adults. The majority of all ALS cases occur sporadically (sALS). Symptoms of ALS are caused by a progressive degeneration of motor neurons located in the motor cortex and spinal cord. The question arises why motor neurons selectively degenerate in ALS, while other cells and systems appear to be spared the disease. Members of the intrinsic apoptotic pathway are frequent targets of altered microRNA expression. Therefore, microRNAs and their effects on cell survival are subject of controversial debates. In this study, we investigated the expression of numerous members of the intrinsic apoptotic cascade by qPCR, western blot, and immunostaining in two different regions of the CNS of wobbler mice. Further we addressed the expression of \(\textit {miR-29b-3p}\) targeting BMF, Bax, and, Bak, members of the apoptotic pathway. We show a tissue-specific differential expression of BMF, Bax, and cl...
Background: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the loss of motor neurons in cerebral cortex, brainstem and spinal cord. Numerous studies have demonstrated signs of oxidative... more
Background: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the loss of motor neurons in cerebral cortex, brainstem and spinal cord. Numerous studies have demonstrated signs of oxidative stress in postmortem neuronal tissue, cerebrospinal fluid, plasma and urine of ALS patients, without focusing on the specific processes within motor neurons. Thus, we aimed to investigate the relevance of reactive oxygen species (ROS) detoxification mechanisms and its consequences on the formation of toxic/lethal DNA double strand breaks (DSBs) in the ALS model of the Wobbler mouse.Methods: Live cell imaging in dissociated motor neuronal cultures was used to investigate the production of ROS using Dihydroethidium (DHE). The expression levels of ROS detoxifying molecules were investigated by qPCR as well as Western blots. Furthermore, the expression levels of DNA damage response proteins p53bp1 and H2ax were investigated using qPCR and immunofluorescence...
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The close interaction between the enteric nervous system, microbiome, and brain in vertebrates is an emerging topic of recent studies. Different species such as rat, mouse, and human are currently being used for this purpose, among... more
The close interaction between the enteric nervous system, microbiome, and brain in vertebrates is an emerging topic of recent studies. Different species such as rat, mouse, and human are currently being used for this purpose, among others. The transferability of protocols for tissue isolation and sample collection is not always straightforward. Thus, the present work presents a new protocol for isolation and sample collection of rat myenteric plexus cells for in vivo as well as in vitro studies. With the methods and chemicals described in detail, a wide variety of investigations can be performed with regard to normal physiological as well as pathological processes in the postnatal developing enteric nervous system. The fast and efficient preparation of the intestine as the first step is particularly important. We have developed and described a LIENS chamber to obtain optimal tissue quality during intestinal freezing. Cryosections of the flat, snap-frozen intestine can then be prepar...
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Although the enteric nervous system (ENS) functions largely autonomously as part of the peripheral nervous system (PNS), it is connected to the central nervous system (CNS) via the gut–brain axis. In many neurodegenerative diseases,... more
Although the enteric nervous system (ENS) functions largely autonomously as part of the peripheral nervous system (PNS), it is connected to the central nervous system (CNS) via the gut–brain axis. In many neurodegenerative diseases, pathological changes occur in addition to gastrointestinal symptoms, such as alpha-synuclein aggregates in Parkinson’s disease, which are found early in the ENS. In both the CNS and PNS, vascular endothelial growth factor (VEGF) mediates neuroprotective and neuroregenerative effects. Since the ENS with its close connection to the microbiome and the immune system is discussed as the origin of neurodegenerative diseases, it is necessary to investigate the possibly positive effects of VEGF on enteric neurons. Using laser microdissection and subsequent quantitative RT-PCR as well as immunohistochemistry, for the first time we were able to detect and localize VEGF receptor expression in rat myenteric neurons of different ages. Furthermore, we demonstrate dire...
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The impact of progesterone on neuronal tissues in the central (CNS) and peripheral (PNS) nervous system is of significant scientific and therapeutic interest. Glial and neuronal cells of vertebrates express steroidogenic enzymes, and are... more
The impact of progesterone on neuronal tissues in the central (CNS) and peripheral (PNS) nervous system is of significant scientific and therapeutic interest. Glial and neuronal cells of vertebrates express steroidogenic enzymes, and are able to synthesize progesterone de novo from cholesterol. Progesterone is described to have neuroprotective, neuroreparative, antidegenerative, and antiapoptotic effects in the CNS and the PNS. Thus, first clinical studies promise new therapeutic options using progesterone in the treatment of patients with traumatic brain injury. Additionally, experimental data from different animal models suggest further positive effects of pro-gesterone on neurological diseases like cerebral ischemia, peripheral nerve injury and amyothropic lateral sclerosis. In regard to this future clinical use of progester-one, we discuss in this review the underlying physiological principles of progesterone effects in neuronal tissues. Mechanisms leading to morphological reorg...
Visualization of the weak staining of Iba-1- and TNF-α-labeled microglial and caspase 3-positive neuronal cells in motor cortex tissue of WR mice 20 d.p.n. (A–C) Relation of activated microglial cells (red) and neurons labeled with... more
Visualization of the weak staining of Iba-1- and TNF-α-labeled microglial and caspase 3-positive neuronal cells in motor cortex tissue of WR mice 20 d.p.n. (A–C) Relation of activated microglial cells (red) and neurons labeled with neuronal nuclei antibody (green) in brain tissue of non-symptomatic WR mice. (D–F) Iba-1-labeled microglial cells (red) synthesizing the cytokine TNF-α (green). (G–H) Caspase 3-positive (red) neurons labeled with NeuN (neuronal nuclei antibody) (green). (Scale bar = 20 μm). (TIF 15107 kb)
Research Interests: Biochemistry, Neuroscience, Physiology, Immunology, Mental Health, and 15 moreComputational Biology, Biology, Virology, Inflammation, Immunohistochemistry, Cell Biology, Infectious Diseases, Neurodegeneration, Medicine, Amyotrophic Lateral Sclerosis, Microglia, Astrocytes, Caspase, Antibody, and Tumor Necrosis Factor–α (TNF)
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in humans and remains to have a fatal prognosis. Recent studies in animal models and human ALS patients indicate that increased reactive oxygen species (ROS) play... more
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in humans and remains to have a fatal prognosis. Recent studies in animal models and human ALS patients indicate that increased reactive oxygen species (ROS) play an important role in the pathogenesis. Considering previous studies revealing the influence of ROS on mitochondrial physiology, our attention was focused on mitochondria in the murine ALS model, wobbler mouse. The aim of this study was to investigate morphological differences between wild-type and wobbler mitochondria with aid of superresolution structured illumination fluorescence microscopy, TEM, and TEM tomography. To get an insight into mitochondrial dynamics, expression studies of corresponding proteins were performed. Here, we found significantly smaller and degenerated mitochondria in wobbler motor neurons at a stable stage of the disease. Our data suggest a ROS-regulated, Ox-CaMKII-dependent Drp1 activation leading to disrupted fission-fusi...
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Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, causing degeneration of both upper and lower motor neurons in the central nervous system (CNS). ALS patients suffer from hyperreflexia, spasticity,... more
Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, causing degeneration of both upper and lower motor neurons in the central nervous system (CNS). ALS patients suffer from hyperreflexia, spasticity, paralysis and muscle atrophy and typically die due to respiratory failure 1–5 years after disease onset. In addition to the degeneration of motor neurons on the cellular level, ALS has been associated with neuroinflammation, such as microgliosis. Microglial activation in ALS can either be protective or degenerative to the neurons. Among others, mutations in superoxide dismutase 1 (SOD1), chromosome 9 open reading frame 72 (C9Orf72), transactive response DNA binding protein (TDP) 43 and vacuolar protein sorting-associated protein 54 (VPS54) genes have been associated with ALS. Here, we describe the dual role and functionality of microglia in four different in vivo ALS models and search for the lowest common denominator with respect to the role of mic...
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The wide-ranging influence of vascular endothelial growth factor (VEGF) within the central (CNS) and peripheral nervous system (PNS), for example through effects on axonal growth or neuronal cell survival, is mainly mediated by VEGF... more
The wide-ranging influence of vascular endothelial growth factor (VEGF) within the central (CNS) and peripheral nervous system (PNS), for example through effects on axonal growth or neuronal cell survival, is mainly mediated by VEGF receptor 2 (VEGFR-2). However, the regulation of VEGFR-2 expression during development is not yet well understood. As microRNAs are considered to be key players during neuronal maturation and regenerative processes, we identified the two microRNAs (miRNAs)—miR-129-5p and miR-130a-3p—that may have an impact on VEGFR-2 expression in young and mature sensory and lower motor neurons. The expression level of VEGFR-2 was analyzed by using in situ hybridization, RT-qPCR, Western blot, and immunohistochemistry in developing rats. microRNAs were validated within the spinal cord and dorsal root ganglia. To unveil the molecular impact of our candidate microRNAs, dissociated cell cultures of sensory and lower motor neurons were transfected with mimics and inhibitors...
Research Interests: Genetics, Neuroscience, MicroRNA, Biology, Medicine, and 3 moreSpinal Cord, Molecular sciences, and DDC
Amyotrophic lateral sclerosis (ALS) is a common degenerative disease of the central nervous system concerning a progressive loss of upper and lower motor neurons. While 5%–10% of patients are diagnosed with the inherited form of the... more
Amyotrophic lateral sclerosis (ALS) is a common degenerative disease of the central nervous system concerning a progressive loss of upper and lower motor neurons. While 5%–10% of patients are diagnosed with the inherited form of the disease, the vast majority of patients suffer from the less characterized sporadic form of ALS (sALS). As the wobbler mouse and the ALS show striking similarities in view of phenotypical attributes, the mouse is rated as an animal model for the disease. Recent investigations show the importance of nicotinamide adenine dinucleotide (NAD+) and its producing enzyme nicotinic acid mononucleotide transferase 2 (Nmnat2) for neurodegeneration as well as for the preservation of health of the neuronal cells. Furthermore, it is newly determined that these molecules show significant downregulations in the spinal cord of wobbler mice in the stable phase of disease development. Here, we were able to prove a positive benefit on affected motor neurons from an additiona...
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Amyotrophic lateral sclerosis (ALS) is one of the most common incurable motor neuron disorders in adults. The majority of all ALS cases occur sporadically (sALS). Symptoms of ALS are caused by a progressive degeneration of motor neurons... more
Amyotrophic lateral sclerosis (ALS) is one of the most common incurable motor neuron disorders in adults. The majority of all ALS cases occur sporadically (sALS). Symptoms of ALS are caused by a progressive degeneration of motor neurons located in the motor cortex and spinal cord. The question arises why motor neurons selectively degenerate in ALS, while other cells and systems appear to be spared the disease. Members of the intrinsic apoptotic pathway are frequent targets of altered microRNA expression. Therefore, microRNAs and their effects on cell survival are subject of controversial debates. In this study, we investigated the expression of numerous members of the intrinsic apoptotic cascade by qPCR, western blot, and immunostaining in two different regions of the CNS of wobbler mice. Further we addressed the expression of miR-29b-3p targeting BMF, Bax, and, Bak, members of the apoptotic pathway. We show a tissue-specific differential expression of BMF, Bax, and cleaved-Caspase ...
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ABSTRACTThe sex hormone progesterone is mainly known as a key factor in establishing and maintaining pregnancy. In addition, progesterone has been shown to induce morphological changes in the central and peripheral nervous system by... more
ABSTRACTThe sex hormone progesterone is mainly known as a key factor in establishing and maintaining pregnancy. In addition, progesterone has been shown to induce morphological changes in the central and peripheral nervous system by increasing dendrito‐, spino‐, and synaptogenesis in Purkinje cells (Wessel et al.: Cell Mol Life Sci (2014a) 1723–1740) and increasing axonal outgrowth in dorsal root ganglia (Olbrich et al.: Endocrinology (2013) 3784–3795). These effects mediated mainly by the classical progesterone receptors (PRs) A and B seem to be limited to young neurons. It may be assumed that microRNAs (miRNAs), which are potent regulators of nervous system maturation and degeneration, are also involved in the regulation of progesterone‐mediated neuronal plasticity by altering the expression patterns of the corresponding PR A/B receptors (Theis and Theiss: Neural Regen Res (2015) 547–549, Pieczora et al.: Cerebellum (2017) 376–387). This review critically discusses current data on...
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AimsVascular endothelial growth factor (VEGF) is a hallmark of glioblastoma multiforme (GBM) and plays an important role in brain development and function. Recently, it has been reported that treatment of GBM patients with bevacizumab, an... more
AimsVascular endothelial growth factor (VEGF) is a hallmark of glioblastoma multiforme (GBM) and plays an important role in brain development and function. Recently, it has been reported that treatment of GBM patients with bevacizumab, an anti‐VEGF antibody, may cause a decline in neurocognitive function and compromise quality of life. Therefore, we investigated the effects of VEGF and bevacizumab on the morphology and on survival of neurons and glial cells.MethodsDissociated cortical and hippocampal cell cultures of juvenile rats were treated with VEGF, bevacizumab, and VEGF + bevacizumab. Neuronal and glial cell viability was analyzed, and the morphology of neurons was objectified by morphometric analysis.ResultsIn cortical cultures, bevacizumab significantly decreased the number of neurons after 20 days and the number of glial cells subsequent 30 days. Additionally, an increase in the dendritic length of cortical neurons was obvious after 10 days of incubation with bevacizumab, b...
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Vascular endothelial growth factor (VEGF) is well known as the growth factor with wide-ranging functions even in the central nervous system (CNS). Presently, most attention is given to the investigation of its role in neuronal protection,... more
Vascular endothelial growth factor (VEGF) is well known as the growth factor with wide-ranging functions even in the central nervous system (CNS). Presently, most attention is given to the investigation of its role in neuronal protection, growth and maturation processes, whereby most effects are mediated through VEGF receptor 2 (VEGFR-2). The purpose of our current study is to provide new insights into the impact of VEGF on immature and mature Purkinje cells (PCs) in accordance with maturity and related receptor expression. Therefore, to expand our knowledge of VEGF effects in PCs development and associated VEGFR-2 expression, we used cultivated organotypic cerebellar slice cultures in immunohistochemical or microinjection studies, followed by confocal laser scanning microscopy (CLSM) and morphometric analysis. Additionally, we incorporated in our study the method of laser microdissection, followed by quantitative polymerase chain reaction (qPCR). For the first time we could show th...
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Research Interests: Endocrinology, Medicine, Birth Weight, Pregnancy, Progesterone, and 15 moreHumans, Internal Medicine, Female, Young Adult, HELLP Syndrome, Adult, Maternal Age, Gestational Age, Estradiol, Radioimmunoassay, Vascular Endothelial Growth Factor, Case Control Studies, Pre Eclampsia, Eclampsia, and Paediatrics and reproductive medicine
The vascular endothelial growth factor (VEGF) is well known for its wide-ranging functions, not only in the vascular system, but also in the central (CNS) and peripheral nervous system (PNS). To study the role of VEGF in neuronal... more
The vascular endothelial growth factor (VEGF) is well known for its wide-ranging functions, not only in the vascular system, but also in the central (CNS) and peripheral nervous system (PNS). To study the role of VEGF in neuronal protection, growth and maturation processes have recently attracted much interest. These effects are mainly mediated by VEGF receptor 2 (VEGFR-2). Current studies have shown the age-dependent expression of VEGFR-2 in Purkinje cells (PC), promoting dendritogenesis in neonatal, but not in mature stages. We hypothesize that microRNAs (miRNA/miR) might be involved in the regulation of VEGFR-2 expression during the development of PC. In preliminary studies, we performed a miRNA profiling and identified miR204-5p as a potential regulator of VEGFR-2 expression. In the recent study, organotypic slice cultures of rat cerebella (postnatal day (p) 1 and 9) were cultivated and VEGFR-2 expression in PC was verified via immunohistochemistry. Additionally, PC at age p9 an...
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Previous studies had demonstrated that the optic tecta of left and right brain halves reciprocally inhibit each other in birds. In mammals, the superior colliculus receives inhibitory GABAergic input from the basal ganglia via both the... more
Previous studies had demonstrated that the optic tecta of left and right brain halves reciprocally inhibit each other in birds. In mammals, the superior colliculus receives inhibitory GABAergic input from the basal ganglia via both the ipsilateral and the contralateral substantia nigra pars reticulata (SNr). This contralateral SNr projection is important in intertectal inhibition. Since the basal ganglia are evolutionary conserved, the tectal projections of SNr may show a similar pattern in birds. Therefore, SNr could be a relay station in an indirect tecto-tectal pathway constituting the neuronal substrate for the tecto-tectal inhibition. To test this hypothesis, we performed bilateral anterograde and retrograde tectal tracing combined with γ-amino butyric acid (GABA) immunohistochemistry in pigeons. Suprisingly, the SNr has only ipsilateral projections to the optic tectum and these are non-GABAergic. Inhibitory GABAergic input to the contralateral optic tectum arises instead from ...
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Research Interests: Neuroscience, Pathology, Immunology, Biology, Inflammation, and 15 moreMotor neuron, Medicine, Amyotrophic Lateral Sclerosis, Mice, Animals, Neuroinflammation, Microglia, Cell Death, Motor Cortex, Neurons, Clinical Sciences, Glial Fibrillary Acidic Protein, DDC, Neurosciences, and Inflammation Mediators
ATOH8 is a bHLH transcription factor playing roles in a variety of developmental processes such as neurogenesis, differentiation of pancreatic precursor cells, development of kidney and muscle, and differentiation of endothelial cells.... more
ATOH8 is a bHLH transcription factor playing roles in a variety of developmental processes such as neurogenesis, differentiation of pancreatic precursor cells, development of kidney and muscle, and differentiation of endothelial cells. PPP3CB belongs to the catalytic subunit of the serine/threonine phosphatase, calcineurin, which can dephosphorylate its substrate proteins to regulate their physiological activities. In our study, we demonstrated that ATOH8 interacts with PPP3CB in vitro with different approaches. We show that the conserved catalytic domain of PPP3CB interacts with both the N-terminus and the bHLH domain of ATOH8. Although the interaction domain of PPP3CB is conserved among all isoforms of calcineurin A, ATOH8 selectively interacts with PPP3CB instead of PPP3CA, probably due to the unique proline-rich region present in the N-terminus of PPP3CB, which controls the specificity of its interaction partners. Furthermore, we show that inhibition of the interaction with calc...
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The impact of progesterone on neuronal tissues in the central (CNS) and peripheral (PNS) nervous system is of significant scientific and therapeutic interest. Glial and neuronal cells of vertebrates express steroidogenic enzymes, and are... more
The impact of progesterone on neuronal tissues in the central (CNS) and peripheral (PNS) nervous system is of significant scientific and therapeutic interest. Glial and neuronal cells of vertebrates express steroidogenic enzymes, and are able to synthesize progesterone de novo from cholesterol. Progesterone is described to have neuroprotective, neuroreparative, anti-degenerative, and anti-apoptotic effects in the CNS and the PNS. Thus, the first clinical studies promise new therapeutic options using progesterone in the treatment of patients with traumatic brain injury. Additionally, experimental data from different animal models suggest further positive effects of progesterone on neurological diseases such as cerebral ischemia, peripheral nerve injury and amyothropic lateral sclerosis. In regard to this future clinical use of progesterone, we discuss in this review the underlying physiological principles of progesterone effects in neuronal tissues. Mechanisms leading to morphologica...
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Research Interests: Biology, Medicine, Signal Transduction, Anatomy, Mice, and 4 moreAnimals, Peptides, Pectoral Girdle, and Chick embryo
The basic helix-loop-helix transcription factor Math6 was shown to have important regulatory functions during many developmental events. However, a systematic description of Math6 expression during mouse embryonic development is up to now... more
The basic helix-loop-helix transcription factor Math6 was shown to have important regulatory functions during many developmental events. However, a systematic description of Math6 expression during mouse embryonic development is up to now still lacking. We carried out this study to show Math6 expression at different stages of mouse embryonic development aiming to provide a wide insight into the regulatory functions during the mouse organogenesis. Using immunohistochemistry, we could show that Math6 expression is activated in the inner cell mass at the blastocyst stage and in the neural tube as well as somatic and splanchnic mesoderm at stage E8.5. At stages E8.5 and E10.5, Math6 transcripts were detected in the myotome, neural tube, pharyngeal arches, foregut and heart. At stages E11.5 and E12.5, Math6 transcripts were accumulated in the developing brain, heart, limb buds and liver. The heterozygous transgenic mouse embryos carrying EGFP-Cre under the Math6 promoter were used to analyze Math6 expression at later stages by means of immunohistochemistry against EGFP protein. EGFP was observed in the neural tube, heart, lung, skeletal muscle, skin, cartilage, trachea and aorta. We have observed Math6 expression in various organs at early and late stages of mouse development, which illustrates the involvement of Math6 in multiple developmental events.
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Arthrofibrosis (af) is defined as a fibrosing disease of the synovial membrane, after joint operations, with painful restricted range of motion. The aim of this paper was to describe the histopathological substrate of af, hitherto only... more
Arthrofibrosis (af) is defined as a fibrosing disease of the synovial membrane, after joint operations, with painful restricted range of motion. The aim of this paper was to describe the histopathological substrate of af, hitherto only defined by clinical criteria. Based on a group of 222 tissue samples, the characteristic changes to af were analyzed. The control group comprised 29 cases with neosynovialis of the indifferent type. Due to cytoplasmic SM-actin positivity and the absence of specific cytoplasmic reactivity in CD 68 representation, af fibroblasts were characterized as myofibroblasts. In confocal laser-scanning microscopy, β-catenin-positive aggregates were detected in the cytoplasm. Over and above this, unequivocal colocalization of β-catenin and the tight junction protein ZO-1 became manifest, particularly on the cell membrane and, partly, in the cytoplasm. A threshold value of 20 β-catenin-positive cells/HPF was determined. This enables the histopathological diagnosis of an af to be made (sensitivity: 0.733, specificity: 0.867). Af is a fibrosing disease of the synovial membrane with variable grade of fibrotization (fibroblast cellularity). A threshold value of 20 β-catenin-positive fibroblasts per HPF was defined, which enables the histopathological diagnosis of af.
Research Interests: Pathology, Biology, Immunohistochemistry, Confocal Microscopy, Medicine, and 15 moreBiopsy, Humans, Fibrosis, Myofibroblasts, Clinical Sciences, Fibroblast, Biological markers, Confocal, Cytoplasm, Predictive value of tests, Case Control Studies, Postoperative Complications, Severity of Illness Index, Colocalization, and Joint diseases
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The neuronal growth cone plays a crucial role in the development of the nervous system. This highly motile structure leads the axon to its final destination by translating guidance cues into cytoskeletal rearrangements. Recently, vascular... more
The neuronal growth cone plays a crucial role in the development of the nervous system. This highly motile structure leads the axon to its final destination by translating guidance cues into cytoskeletal rearrangements. Recently, vascular endothelial growth factor (VEGF), which is essential for angiogenesis and vascular sprouting, has been found to exert a trophic activity also on neurons, leading to an increased axonal outgrowth, similar to the well-known nerve growth factor (NGF). The neurotrophic properties of VEGF are likely to be promoted via the VEGF receptor 2 (VEGFR-2) and neuropilin-1 (NRP-1). In the long term, VEGF attracts and influences the growth cone velocity and leads to growth cone enlargement. The present study focuses on immediate VEGF effects using RFP-actin and GFP-NF-M microinjected chicken dorsal root ganglia for live cell imaging of the neuronal growth cone. We analyzed actin and neurofilament dynamics following VEGF and NGF treatment and compared the effects. Furthermore, key signaling pathways of VEGF were investigated by specific blocking of VEGFR-2 or NRP-1. With the aid of confocal laser scanning microscopy and stimulated emission depletion microscopy, we show for the first time that VEGF has a quick effect on the actin-cytoskeleton, since actin rearrangements were identifiable within a few minutes, leading to a dramatically increased motion. Moreover, these effects were strongly enhanced by adding both VEGF and NGF. Most notably, the effects were inhibited by blocking VEGFR-2, therefore we propose that the immediate effects of VEGF on the actin-cytoskeleton are mediated through VEGFR-2.
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The purpose of the present study was to investigate the effects of vascular endothelial growth factor (VEGF) on gap junctional intercellular communication (GJIC), cell proliferation, and cell dynamics in primary astrocytes. VEGF is known... more
The purpose of the present study was to investigate the effects of vascular endothelial growth factor (VEGF) on gap junctional intercellular communication (GJIC), cell proliferation, and cell dynamics in primary astrocytes. VEGF is known as a dimeric polypeptide that potentially binds to two receptors, VEGFR-1 and VEGFR-2, however many effects are mediated by VEGFR-2, for example, actin polymerization, forced cell migration, angiogenesis, and cell proliferation. Recently it has been shown that in case of hypoxia, ischemia or injury VEGF is upregulated to stimulate angiogenesis and cell proliferation. Besides this, VEGF reveals a potent therapeutical target for averting tumor vascularization, emerging in bevacizumab, the first humanized anti-VEGF-A antibody for treating recurrent Glioblastoma multiforme. To expand our knowledge about VEGF effects in glial cells, we cultivated rat astrocytes in medium containing VEGF for 1 and 2 days. To investigate the effects of VEGF on GJIC, we mic...