A5081343538- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Tryptophan and brain disorders
- Erythrocyte Function and Pathophysiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Supramolecular Self-Assembly in Materials
- Alzheimer's disease research and treatments
- Adenosine and Purinergic Signaling
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Treatment of Major Depression
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Cell Image Analysis Techniques
- Receptor Mechanisms and Signaling
- Epigenetics and DNA Methylation
- Advanced Fluorescence Microscopy Techniques
- Sphingolipid Metabolism and Signaling
- Amyotrophic Lateral Sclerosis Research
- Endoplasmic Reticulum Stress and Disease
- Advanced Chemical Sensor Technologies
- Genetics and Neurodevelopmental Disorders
- Olfactory and Sensory Function Studies
- Neurobiology and Insect Physiology Research
University of Ljubljana
2015-2025
Celica (Slovenia)
2015-2025
National Institute of Chemistry
2020
Czech Academy of Sciences, Institute of Physiology
2007
Institute of Oncology Ljubljana
2003
Astrocytes appear to communicate with each other as well neurons via ATP. However, the mechanisms of ATP release are controversial. To explore whether stimuli that increase [Ca2+]i also trigger vesicular from astrocytes, we labeled ATP-containing vesicles fluorescent dye quinacrine, which exhibited a significant co-localization atrial natriuretic peptide. The confocal microscopy study revealed quinacrine-loaded displayed mainly non-directional spontaneous mobility relatively short track...
Adult neurogenesis is regulated by a number of cellular players within the neurogenic niche. Astrocytes participate actively in brain development, regulation mature central nervous system (CNS), and plasticity. They are important regulators local environment adult niches through secretion diffusible morphogenic factors, such as Wnts. control niche also membrane-associated however, identity these factors mechanisms involved largely unknown. In this study, we sought to determine underlying our...
Abstract Astrocytes, a subtype of glial cells, have numerous characteristics that were previously considered exclusive for neurons. One these is cytosolic [Ca 2+ ] oscillation controls the release chemical transmitter glutamate and atrial natriuretic peptide. These messengers appear to be released from astrocytes via Ca ‐dependent exocytosis. In present study, patch‐clamp membrane capacitance measurements used monitor changes in area single astrocyte, while photolysis caged calcium compounds...
Kiss-and-run exocytosis, consisting of reversible fusion between the vesicle membrane and plasma membrane, is considered to lead full after stimulation vesicles containing classical transmitters. However, whether this also case in peptidergic unknown. Previously, we have observed that spontaneous neuropeptide discharge from a single slower than stimulated release, because kinetic constraints pore opening. To explore slow release reflects relatively narrow pore, analyzed permeation FM 4-64...
Abstract Intermediate filament (IF) proteins upregulation is a hallmark of astrocyte activation and reactive gliosis, but its pathophysiological implications remain incompletely understood. A recently reported association between IFs directional mobility peptidergic vesicles allows us to hypothesize that affect vesicle dynamics exocytosis‐mediated communication with neighboring cells. Here, we ask whether the trafficking recycling (i.e., those fused then retrieved from plasma membrane)...
Astrocytes are non-neuronal cells in the CNS, which, like neurons, capable of releasing neuroactive molecules. However, mechanism release is ill defined. In this study, we investigated atrial natriuretic peptide (ANP) from cultured cortical astrocytes by confocal microscopy. To study discharge hormone, transfected with a construct to express pro-ANP fused emerald green fluorescent protein (ANP.emd). The transfection ANP.emd resulted puncta cytoplasm that represent secretory organelles. If...
Aquaporin 4 (AQP4) is the predominant water channel in brain, expressed mainly astrocytes and involved transport physiologic pathologic conditions. Besides classical isoforms M1 (a) M23 (c), additional ones may be present at plasma membrane, such as recently described AQP4b, d, e, f. Water permeability regulation by AQP4 involve several processes, conformational changes, extent arrangement of channels dynamics trafficking to/from membrane. To test whether vesicular affects abundance we...
The intermediate filament (nanofilament) protein nestin is a marker of neural stem cells, but its role in neurogenesis, including adult remains unclear. Here, we investigated the neurogenesis nestin-deficient (Nes-/-) mice. We found that proliferation Nes-/- cells was not altered, hippocampal dentate gyrus mice increased. Surprisingly, proneurogenic effect deficiency mediated by function astrocyte niche. Through Notch signaling from astrocytes to negatively regulates neuronal differentiation...
Severe coronavirus infections, including SARS-CoV-2, can cause neurological symptoms, but the underlying neurotropic mechanisms are unclear. Experiments with SARS-CoV-2 variants B.1.258.17, B.1.1.7, and BA.5.3.2 (termed wild-type, alpha omicron, respectively) revealed that human astrocytes, not neurons, support viral proliferation. During COVID-19 pandemic, new virus exhibited milder disease progression. A retrospective study of patients infected by wild-type or was conducted to test whether...
It is believed that in regulated exocytosis the vesicle membrane fuses with plasma response to a physiological stimulus. However, absence of stimulation, repetitive transient fusion events are also observed, reflecting stable state. The mechanisms by which initial pore attains stability poorly understood. We modelled energetic taking into account anisotropic, intrinsic shape constituents and their in-plane ordering local curvature membrane. used cell-attached capacitance techniques monitor...
In the brain, astrocytes provide metabolic and trophic support to neurones. Failure in executing astroglial homeostatic functions may contribute initiation propagation of diseases, including Alzheimer disease (AD), characterized by a progressive loss neurones over years. Here, we examined whether from mice model AD isolated presymptomatic phase exhibit alterations vesicle traffic, vesicular peptide release purinergic calcium signaling. cultured newborn wild‐type (wt) 3xTg‐AD mouse, secretory...
Abstract Ketamine is an antidepressant with rapid therapeutic onset and long-lasting effect, although the underlying mechanism(s) remain unknown. Using FRET-based nanosensors we found that ketamine increases [cAMP] i in astrocytes. Membrane capacitance recordings, however, reveal fundamentally distinct mechanisms of effects on vesicular secretion: a rise facilitated, whereas inhibited exocytosis. By directly monitoring cholesterol-rich membrane domains fluorescently tagged...
Hormones are released from cells by passing through an exocytotic pore that forms after vesicle and plasma membrane fusion. In stimulated exocytosis content is discharged swiftly. Although rapid discharge has also been proposed to mediate basal secretion, this not studied directly. We investigated hormone release preloading fluorescent peptides into single vesicles. The discharge, monitored with confocal microscopy, was compared the simultaneous loading of FM styryl dye. vesicles 4-64 (4...
Abstract Astrocytes are increasingly viewed as playing many roles in the integration of brain function. These cells store among other gliotransmitters also neuroactive peptides membrane bound vesicles, trafficking and release which, may be changed altered conditions, therefore affecting physiological status neurons. In general, peptidergic membrane‐bound secretory vesicles fuse with plasma process exocytosis. Some them retrieved from to recycled back into cytosol. The mobility retrieving...
Abstract In the brain, astrocytes signal to neighboring cells by release of chemical messengers (gliotransmitters) via regulated exocytosis. Recent studies uncovered a potential role signaling lipids in modulation Hence, we investigated whether sphingosine and structural analog fingolimod/FTY720, recently introduced therapeutic for multiple sclerosis, affect (i) intracellular vesicle mobility (ii) cargo discharge from cultured rat astrocytes. Distinct types vesicles, peptidergic,...
We studied whether regulated exocytosis affects the glutamate transporter density in cultured astrocytes, which expression of a fluorescently labeled excitatory amino acid 2 (EAAT2-EGFP) predominantly plasma membrane. The addition ionomycin that elevates cytosolic Ca2+ strongly increased fluorescence FM 4-64 membrane area dye, confirming presence transfected astrocytes. However, concomitant with Ca2+-dependent increase, induced significant steady-state decrease EAAT2-EGFP fluorescence. This...
Ketamine is an anesthetic that exhibits analgesic, psychotomimetic, and rapid antidepressant effects are of particular neuropharmacological interest. Recent studies revealed astrocytic Ca(2+) signaling regulated exocytosis as ketamine-targeted processes. Thus high-resolution cell-attached membrane capacitance measurements were performed to examine the influence ketamine on individual vesicle interactions with plasma in cultured rat astrocytes. evoked long-lasting bursts repetitive opening...
In some lysosomal storage diseases (LSD) cholesterol accumulates in vesicles. Whether increased vesicle affects fusion with the plasmalemma, where pore, a channel between lumen and extracellular space, is formed, unknown. Super-resolution microscopy revealed that after stimulation of exocytosis, pituitary lactotroph vesicles discharge which transfers to plasmalemma. Cholesterol depletion lactotrophs astrocytes, both exhibiting Ca2+-dependent exocytosis regulated by distinct Ca2+sources,...