A5025425341- Neuroscience and Neural Engineering
- Cell Image Analysis Techniques
- Neuroscience and Neuropharmacology Research
- 3D Printing in Biomedical Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Advanced Fluorescence Microscopy Techniques
- Neural dynamics and brain function
- Immune Response and Inflammation
- Extracellular vesicles in disease
- Medicinal Plants and Bioactive Compounds
- Gut microbiota and health
- S100 Proteins and Annexins
- Bioinformatics and Genomic Networks
- Photoreceptor and optogenetics research
- 14-3-3 protein interactions
- Neuroscience, Education and Cognitive Function
- Microfluidic and Bio-sensing Technologies
- Probiotics and Fermented Foods
- Infectious Diseases and Mycology
- AI in cancer detection
- Medicinal Plants and Neuroprotection
- Lipid Membrane Structure and Behavior
- Cell Adhesion Molecules Research
- Cellular transport and secretion
University of Antwerp
2014-2024
Abstract Impaired neuronal network function is a hallmark of neurodevelopmental and neurodegenerative disorders such as autism, schizophrenia, Alzheimer’s disease typically studied using genetically modified cellular animal models. Weak predictive capacity poor translational value these models urge for better human derived in vitro The implementation induced pluripotent stem cells (hiPSCs) allows studying pathologies differentiated disease-relevant patient-derived cells. However, the...
Axonal Charcot-Marie-Tooth neuropathies (CMT type 2) are caused by inherited mutations in various genes functioning different pathways. The types of and multiplicity reflect the clinical genetic heterogeneity CMT2 disease, which complicates its diagnosis has inhibited development therapies. Here, we used patient-derived pluripotent stem cells (iPSCs) to identify common hallmarks axonal degeneration shared subtypes. We compared cellular phenotypes neurons differentiated from patient iPSCs...
Long considered to fluctuate between pro- and anti-inflammatory states, it has now become evident that microglia occupy a variegated phenotypic landscape with relevance aging neurodegeneration. However, whether specific microglial subsets converge in or contribute both processes eventually affect brain function is less clear. To investigate this, we analyzed heterogeneity tauopathy mouse model (K18-seeded P301L) an accelerated (Senescence-Accelerated Mouse-Prone 8, SAMP8) using cellular...
Epidemiologic associations and preclinical studies suggest that amyloid pathology observed in the brain may be preceded by gastrointestinal amyloidosis.We identify a pathogenic program becomes activated enteric nervous system after exposure to bacterial amyloids, show serum A3 is an important self-amplifying mediator of this proinflammatory response.responsible for SAA3 production, attenuated curli-and recombinant SAA3-induced Saa3 up-regulation, DNA damage, replication glia.CONCLUSIONS: Our...
Abstract In the last decade, extracellular vesicles (EVs) have become a hot topic. The findings on EVs content and effects made them major field of interest in cancer research. EVs, are able to be internalized through integrins expressed parental cells, tissue specific manner, as key step progression pre-metastatic niche formation. However, this specificity might lead new opportunities treatment by using devices for drug delivery. For future applications cancer, improved protocols methods...
Most neurological disorders display impaired synaptic connectivity. Hence, modulation of synapse formation may have therapeutic relevance. However, the high density and small size synapses complicate their quantification. To improve synapse-oriented screens, we analyzed labeling performance synapse-targeting antibodies on neuronal cell cultures using segmentation-independent image analysis based sliding window correlation. When assessing pairwise colocalization, a common readout for mature...
Functionally related neurons assemble into connected networks that process and transmit electrochemical information. To do this in a coordinated manner, the number strength of synaptic connections is tightly regulated. Synapse function relies on microtubule (MT) cytoskeleton, dynamics which are turn controlled by plethora MT-associated proteins, including MT-stabilizing protein Tau. Although mutations Tau-encoding MAPT gene underlie set neurodegenerative disorders, termed tauopathies, exact...
Neurodevelopmental and neurodegenerative disorders are characterized by subtle alterations in synaptic connections perturbed neuronal network functionality. A hallmark of connectivity is the presence dendritic spines, micron-sized protrusions shaft that compartmentalize single synapses to fine-tune strength. However, accurate quantification spine density morphology mature networks hampered lack targeted labeling strategies. To resolve this, we have optimized a method deliver cell-impermeable...
Therapeutic developments for neurodegenerative disorders are redirecting their focus to the mechanisms that contribute neuronal connectivity and loss thereof. Using a high-throughput microscopy pipeline integrates morphological functional measurements, we found inhibition of dual leucine zipper kinase (DLK) increased in primary cortical cultures. This neuroprotective effect was not only observed basal conditions but also cultures depleted from antioxidants which microtubule stability...
Upon maturation, primary neuronal cultures form an interconnected network based on neurite outgrowth and synaptogenesis in which spontaneous electrical activity arises. Measurement of allows quantification health maturation. A fluorescent indicator was used to monitor secondary calcium influxes after the occurrence action potentials, allowing us examine hippocampal via confocal live cell imaging. Subsequently, nuclear staining with DAPI accurate segmentation. To analyze recording a robust,...
The Fragile X mental retardation protein (FMRP) is involved in many cellular processes and it regulates synaptic network development neurons. Its absence known to lead intellectual disability, with a wide range of comorbidities including autism. Over the past decades, FMRP research focused on abnormalities both glutamatergic GABAergic signaling, an altered balance between excitation inhibition has been hypothesized underlie clinical consequences protein. Using Fmrp knockout mice, we studied...
Abstract Long considered to fluctuate between pro- and anti-inflammatory states, it has now become evident that microglia occupy a variegated phenotypic landscape with relevance aging neurodegeneration. However, whether specific microglial subsets converge in or contribute both processes eventually affect brain function is less clear. To investigate this, we analyzed heterogeneity tauopathy mouse model (K18-seeded P301L) an accelerated (senescence prone 8, SAMP8) using cellular indexing of...
Neurological disorders are defined by synaptic dysfunction. We present a workflow to quantify morphological and functional aspects of connectivity in neuronal cultures obtain an integrated readout. describe steps for measuring synchronous calcium bursting GCaMP6f-transduced neurons labeling mature synapses using proximity ligation assay. The integration information from the same provides rich fingerprint connectivity, deployable different experimental conditions. For complete details on use...
A shift from conventional cytology to a molecular approach could improve cervical cancer screening. This proof-of-concept study aims develop high-content imaging platform for the simultaneous detection of multiple biomarkers disease. Liquid-based (LBC) samples were used optimize dual ProExC/Ki-67 immunofluorescence staining protocol SurePath-fixed cells. The and automated these was performed using BD Pathway 435 system. ability detect dysplastic cells assessed keratinocytes spiked with...
Abstract A vast set of neurological disorders is associated with impaired synaptic connectivity. Therefore, modulation synapse formation could have therapeutic relevance. However, the high density and small size synapses make their quantification a challenging task. To improve reliability synapse-oriented drug screens, we evaluated panel synapse-targeting antibodies for labeling specificity on hippocampal cortical cell cultures using quantitative immunofluorescence microscopy. For those that...
During brain development, orchestrated activation of genetic programs, as well spontaneous electrical activity guide the correct wiring neuronal networks. Mature networks are characterized by expression synaptic markers, synchronized and presence dendritic spines, tiny protrusions from shaft that compartmentalize single synapses to ensure optimal regulation strength. While neurodevelopmental disorders such schizophrenia thought result defective network formation, neurodegenerative like...
Event Abstract Back to Microscopy-based evaluation of synaptic connectivity in primary neuronal culture. Peter Verstraelen1*, Marlies Verschuuren1, Rony Nuydens2, Larsen2, Jean-Pierre Timmermans1 and Winnok H. De Vos1 1 University Antwerp, Lab Cell Biology Histology, Belgium 2 Janssen Research & Development, Development treatments for neurodegenerative disorders demands understanding the mechanisms that contribute plasticity loss thereof. This turn, requires methods quantify a network with...
Abstract Background Therapeutic developments for neurodegenerative disorders are redirecting their focus to the mechanisms that contribute synaptic plasticity and loss thereof. Identification of novel regulators requires a method quantify neuronal network connectivity with high accuracy throughput. To meet this demand, we have established microscopy-based pipeline integrates morphological functional correlates in primary culture. Results We unveiled signature was specific cell type culture...