A5003338541- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Nuclear Receptors and Signaling
- CRISPR and Genetic Engineering
- RNA regulation and disease
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA and protein synthesis mechanisms
- Axon Guidance and Neuronal Signaling
- Glioma Diagnosis and Treatment
- Viral Infections and Immunology Research
- Epilepsy research and treatment
- Neuroscience and Neural Engineering
- Microtubule and mitosis dynamics
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Cardiac electrophysiology and arrhythmias
- Trace Elements in Health
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Autoimmune Neurological Disorders and Treatments
- MicroRNA in disease regulation
- Chromatin Remodeling and Cancer
- Hippo pathway signaling and YAP/TAZ
RWTH Aachen University
2020-2025
Universitätsklinikum Aachen
2023-2025
University of Bonn
2013-2023
University Hospital Bonn
2020-2023
Radboud University Nijmegen
2005-2011
Radboud Institute for Molecular Life Sciences
2005-2010
Radboud University Medical Center
2005-2010
It is clear that neural differentiation from human pluripotent stem cells generates are developmentally immature. Here, we show the let-7 plays a functional role in developmental decision making of progenitors, controlling whether these make neurons or glia. Through gain- and loss-of-function studies on both tissue derived cells, our data specifically regulates this context by regulation key chromatin-associated protein, HMGA2. Furthermore, provide evidence let-7/HMGA2 circuit acts HES5,...
Abstract Temporal lobe epilepsy (TLE) is the most common focal seizure disorder in adults. In many patients, transient brain insults, including status epilepticus (SE), are followed by a latent period of epileptogenesis, preceding emergence clinical seizures. experimental animals, transcriptional upregulation Ca V 3.2 T-type 2+ -channels, resulting an increased propensity for burst discharges hippocampal neurons, important trigger epileptogenesis. Here we provide evidence that...
Neuronal degeneration represents a pathogenetic hallmark after different brain insults, such as ischemia and status epilepticus (SE). Excessive release of glutamate triggered by pathophysiologic synaptic activity has been put forward key mechanism in this context. In response to activity, multiple signaling cascades are activated that ultimately initiate expression specific sets genes, which may decide between neuronal survival versus death. Recently, core set genes [“activity-regulated...
Autoimmune limbic encephalitis (ALE) presents with new-onset mesial temporal lobe seizures, progressive memory disturbance, and other behavioral cognitive changes. CD8 T cells are considered to play a key role in those cases where autoantibodies (ABs) target intracellular antigens or no ABs were found. Assessment of such patients clinical challenge, novel noninvasive imaging biomarkers urgently needed. Here, we demonstrate that visualization the translocator protein (TSPO) [
Abstract The balance of excitation and inhibition is essential for cortical information processing, relying on the tight orchestration underlying subcellular processes. Dynamic transcriptional control by DNA methylation, catalyzed methyltransferases (DNMTs), demethylation, achieved ten–eleven translocation (TET)-dependent mechanisms, proposed to regulate synaptic function in adult brain with implications learning memory. However, focus so far laid excitatory neurons. Given crucial role...
Objective Limbic encephalitis (LE) comprises a spectrum of inflammatory changes in affected brain structures including the presence autoantibodies and lymphoid cells. However, potential distinct lymphocyte subsets alone to elicit key clinicopathological sequelae LE potentially inducing temporal lobe epilepsy (TLE) with chronic spontaneous seizures hippocampal sclerosis (HS) is unresolved. Methods Here, we scrutinized pathogenic consequences emerging from CD8 + T cells targeting neurons by...
Transient brain insults, including status epilepticus (SE), can trigger a period of epileptogenesis during which functional and structural reorganization neuronal networks occurs resulting in the onset focal epileptic seizures. In recent years, mechanisms that regulate dynamic transcription individual genes thereby contribute to development hyperexcitable network have been elucidated. Our own results shown early growth response 1 (Egr1) transiently increase expression T-type...
Developmental brain tumors harboring BRAFV600E somatic mutation are diverse. Here, we describe molecular factors that determine BRAFV600E-induced tumor biology and function.Intraventricular in utero electroporation combination with the piggyBac transposon system was utilized to generate developmental neoplasms, which were comprehensively analyzed regard growth using near-infrared in-vivo imaging, transcript signatures by RNA sequencing, neuronal activity multielectrode arrays.BRAF V600E...
The development of the mouse neocortex in vitro mimics vivo development. Mouse brain cultures can serve as a model system for cortical first 2 wk and adult cortex from to 4 vitro. organotypic slice develop high-frequency network oscillations at γ frequency after exhibit increased heterogeneity variability culture.
Dendritic spines, small protrusions on neuronal dendrites, play a crucial role in brain function by changing shape and size response to neural activity. So far, depth analysis of dendritic spines human tissue is lacking. This study presents comprehensive spine morphology density using unique dataset from 27 patients (8 females, 19 males, aged 18-71) undergoing tumor or epilepsy surgery at three neurosurgery sites. We used acute slices organotypic slice cultures examine classifying them into...
Genetic defects in AP2M1 , which encodes the μ-subunit of adaptor protein complex 2 (AP-2) essential for clathrin-mediated endocytosis (CME), cause a rare form developmental and epileptic encephalopathy (DEE). In this study, we modeled AP2M1-DEE Drosophila melanogaster to gain deeper insights into underlying disease mechanisms. Pan-neuronal knock-down ortholog, AP-2μ resulted consistent heat-sensitive paralysis phenotype altered morphology class IV dendritic arborization (c4da) neurons....
Abstract Cocaine (COC) inhibits the re‐uptake of dopamine. However, dopamine response to COC also depends on inside storage vesicles. The aim this study was investigate whether rats that differentially respond differ in their dopaminergic capacity nucleus accumbens. Total and vesicular levels accumbal as well monoamine transporter‐2 were established high (HR) low responders (LR) novelty rats. Moreover, effects reserpine (RES) COC‐induced increase extracellular investigated. HR displayed...
The functional consequences of single nucleotide polymorphisms associated with episodic brain disorders such as epilepsy and depression are unclear. Allelic associations generalized epilepsies have been reported for rs1883415 (ALDH5A1; succinic semialdehyde dehydrogenase) rs4906902 (GABRB3; GABAA β3), both which present in the 5' regulatory region genes involved γ-aminobutyric acid (GABA) homeostasis. To address their allelic association allele-specific impact on transcriptional regulation...
Transient brain insults including status epilepticus (SE) can initiate a process termed 'epileptogenesis' that results in chronic temporal lobe epilepsy. As consequence, the entire tri-synaptic circuit of hippocampus is fundamentally impaired. A key role epileptogenesis has been attributed to CA1 region as last relay station hippocampal and site aberrant plasticity, e.g. mediated by acquired channelopathies. The transcriptional profiles distinct neurons are highly dynamic during...
Mesial temporal lobe epilepsy with hippocampal sclerosis and a history of febrile seizures is associated common variation at rs7587026, located in the promoter region SCN1A. We sought to explore possible underlying mechanisms. SCN1A expression was analysed biopsy specimens individuals mesial who underwent surgical treatment, neuronal cell loss quantitatively assessed using immunohistochemistry. In healthy individuals, volume measured MRI. Analyses were performed stratified by rs7587026 type....