A5075562148- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Molecular Biology Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Diet and metabolism studies
- Adenosine and Purinergic Signaling
- Lipid Membrane Structure and Behavior
- Neurogenesis and neuroplasticity mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Endoplasmic Reticulum Stress and Disease
- Histone Deacetylase Inhibitors Research
- Bacteriophages and microbial interactions
- Neurological Disease Mechanisms and Treatments
- Peripheral Neuropathies and Disorders
- Industrial Vision Systems and Defect Detection
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Advanced Chemical Sensor Technologies
- Toxin Mechanisms and Immunotoxins
- Sleep and Wakefulness Research
- Chemokine receptors and signaling
- Optical Imaging and Spectroscopy Techniques
Vilnius University
2017-2024
European Molecular Biology Laboratory
2014-2023
University of Cambridge
2011-2016
Abstract Microglia are highly motile glial cells that proposed to mediate synaptic pruning during neuronal circuit formation. Disruption of signaling between microglia and neurons leads an excess immature connections, thought be the result impaired phagocytosis synapses by microglia. However, until now direct has not been reported fundamental questions remain about precise structures phagocytic mechanisms involved. Here we used light sheet fluorescence microscopy follow microglia–synapse...
Abstract It is well-known that dead and dying neurons are quickly removed through phagocytosis by the brain’s macrophages, microglia. Therefore, neuronal loss during brain inflammation has always been assumed to be due of subsequent their apoptotic or necrotic death. However, we report in this article under inflammatory conditions primary rat cultures glia, actively induces Specifically, two bacterial ligands, lipoteichoic acid LPS (agonists glial TLR2 TLR4, respectively), stimulated...
Alzheimer disease is characterized by neuronal loss and brain plaques of extracellular amyloid β (Aβ), but the means which Aβ may induce not entirely clear. Although high concentrations (μm) can direct toxicity to neurons, we find that low concentration (nm) through a microglia-mediated mechanism. In mixed neuronal-glial cultures from rat cerebellum, 250 nm Aβ1–42 (added as monomers, oligomers or fibers) induced about 30% neurons between 2 3 days. This occurred without any increase in...
Microglial phagocytosis of dead or dying neurons can be beneficial by preventing the release damaging and/or pro-inflammatory intracellular components. However, there is now evidence that under certain conditions, such as inflammation, microglia also phagocytose viable neurons, thus executing their death. Such phagocytic cell death may result from exposure phosphatidylserine (PS) other eat-me signals on otherwise a physiological activation sub-toxic insult, and neuronal activated microglia....
Tumour necrosis factor-α (TNF-α) is a pro-inflammatory cytokine, expressed in many brain pathologies and associated with neuronal loss. We show here that addition of TNF-α to neuronal-glial co-cultures increases microglial proliferation phagocytosis, results loss prevented by eliminating microglia. Blocking phagocytosis inhibiting phagocytic vitronectin P2Y6 receptors, or genetically removing opsonin MFG-E8, induced live neurons. Thus appears induce via activation neurons, causing death phagoptosis.
Microglia activated through Toll‐like receptor (TLR)‐2 or ‐4 can cause neuronal death by phagocytosing otherwise‐viable neurons—a form of cell called “phagoptosis.” UDP release from neurons has been shown to provoke microglial phagocytosis via P2Y 6 receptors, but whether inhibition this process affects survival is unknown. We tested here signaling could prevent in inflammatory conditions, and induce phagoptosis stressed viable neurons. find that delayed loss mixed neuronal/glial cultures...
ABSTRACT Microglia participate in synapse remodeling the cortex and hippocampus during mouse postnatal development. Although sex differences microglia activity embryonic development have been reported these regions, it remains unexplored whether show sexually dimorphic features early period, a critical window for formation maturation. Here, we investigated morphological functional of across as well both pre‐ postsynaptic neuronal compartments hippocampus. We found sex‐dependent shift volume...
Abstract Nanomolar β‐amyloid peptide (Aβ) can induce neuronal loss in culture by activating microglia to phagocytose neurons. We report here that this is mediated the bridging protein lactadherin/milk‐fat globule epidermal growth factor‐like factor 8 (MFG‐E8), which released Aβ‐activated microglia, binds co‐cultured neurons and opsonizes for phagocytosis microglia. Aβ stimulated microglial phagocytosis, but did not opsonize phagocytosis. (250 nM) induced delayed mixed glial‐neuronal mouse...
Microglia are brain macrophages, which can undergo multinucleation to give rise multinucleated giant cells that accumulate with ageing and some pathologies. However, the origin, regulation function of multinucleate microglia remain unclear. We found inflammatory stimuli, including lipopolysaccharide, amyloid β, α-synuclein, tumour necrosis factor-α interferon γ, but not interleukin-4, induced cultured microglia: primary rat cortical murine microglial cell line BV-2. Inflammation-induced was...
Microglial research has been constrained by a rolling series of dichotomies such as "resting versus activated" or "M1 M2". This Manichean perspective good bad microglia is in sharp contrast with the wide repertoire microglial functions, exerted from development to aging and diseases, brought light recent years. New designations continuously arising attempt describe different states transcriptomics other readouts may thus easily lead misleading, although unintentional, coupling categories...
Abstract The mature mammalian brain connectome emerges during development via the extension and pruning of neuronal connections. Glial cells have been identified as key players in phagocytic elimination synapses projections. Recently, phosphatidylserine has “eat‐me” signal that guides unnecessary input sources, but associated transduction systems involved such are yet to be described. Here, we Xk‐related protein 8 (Xkr8), a phospholipid scramblase, factor for axons developing brain. We found...
Abstract Background In glioblastoma (GBM), the effects of altered glycocalyx are largely unexplored. The terminal moiety cell coating glycans, sialic acid, is paramount importance for cell-cell contacts. However, acid turnover in gliomas and its impact on tumor networks remain unknown. Methods We streamlined an experimental setup using organotypic human brain slice cultures as a framework exploring glycobiology, including metabolic labeling moieties quantification changes. By live, 2-photon...
Glial cells are fundamental for the pathophysiology of all neurological disorders. Astrocytes, primary homeostatic central nervous system (CNS), exhibit species-specific characteristics, with human astrocytes specifically displaying unique structural and functional features. It is thus essential to investigate human-specific astrocytic responses neuropathology using human-relevant models. Varicose projection (VP) astrocytes, traditionally considered specific humans apes, were suggested...
Detection of neuronal antibodies for autoimmune encephalitis and paraneoplastic neurological syndromes relies on commercially available cell-based assays lineblots. However, lineblots may reveal the presence in patients with various non-autoimmune etiologies. Herein we describe etiologies (cohort B) detectable compare them to definite cases A) differences clinical data. All positive at least one antibody were retrospectively evaluated and/or syndrome between 2016 2022. 39 cohort B 23 A...
Bionanoparticles comprised of naturally occurring monomers are gaining interest in the development novel drug transportation systems. Here we report on stabilisation, cellular uptake, and macrophage clearance nanotubes formed from self-assembling gp053 tail sheath protein vB_EcoM_FV3 bacteriophage. To evaluate potential bacteriophage protein-based as therapeutic nanocarriers, investigated their internalisation into colorectal cancer cell lines professional macrophages that may hinder...
Abstract Microglia are highly motile glial cells that proposed to mediate synaptic pruning during neuronal circuit formation. Disruption of signaling between microglia and neurons leads an excess immature connections, thought be the result impaired phagocytosis synapses by microglia. However, until now direct has not been reported fundamental questions remain about precise structures phagocytic mechanisms involved. Here we used light sheet fluorescence microscopy follow microglia-synapse...
The dynamics of phosphatidylserine in the plasma membrane is a tightly regulated feature eukaryotic cells. Phosphatidylserine (PS) found preferentially inner leaflet membrane. Disruption this asymmetry leads to exposure on cell surface and associated with death, synaptic pruning, blood clotting other cellular processes. Due role widespread functions, an efficient probe needed study them. Currently, few different labelling tools are available; however, these labels have unfavourable...
Fluorescent protein-based Genetically Encoded Voltage Indicators (GEVI) offer a remarkable system for high-throughput screening of membrane potential phenotypes. The GEVI MARINA is derivative from ArcLight, which conversely to ArcLight increases its fluorescence intensity alongside depolarization. Here we created knock-in reporter human iPS cell lines carrying the using SpCas9 programmable nuclease and characterize heterozygous clone.
Traditionally, RNA integrity evaluation is based on ribosomal RNAs (rRNAs). Nevertheless, gene expression studies are usually focused protein coding messenger (mRNAs). As rRNA and mRNA have significant structural functional differences, the assumption that properly represents may not be accurate. Moreover, contrary to whole tissue samples, subcellular preparations such as synaptosomes contain almost no rRNA, thus prohibiting use of traditional rRNA-based methods assess sample integrity. Here...