Antitumor Effects of a New Retinoate of the Fungal Cytotoxin Illudin M in Brain Tumor Models.

While the fungal metabolite illudin M () is indiscriminately cytotoxic in cancer and non-malignant cells, its retinoate showed a greater selectivity for the former, especially in a cerebral context. Illudin M killed malignant glioma cells as well as primary neurons and astrocytes at similarly low concentrations and destroyed their microtubule and glial fibrillary acidic protein (GFAP) networks. In contrast, the ester was distinctly more cytotoxic in highly dedifferentiated U87 glioma cells than in neurons, which were even stimulated to enhanced growth.

Differentiation-Dependent Motility-Responses of Developing Neural Progenitors to Optogenetic Stimulation.

During neural tissue genesis, neural stem/progenitor cells are exposed to bioelectric stimuli well before synaptogenesis and neural circuit formation. Fluctuations in the electrochemical potential in the vicinity of developing cells influence the genesis, migration and maturation of neuronal precursors. The complexity of the environment and the coexistence of various progenitor populations hinder the understanding of the significance of ionic/bioelectric stimuli in the early phases of neuronal differentiation.

Versatility of microglial bioenergetic machinery under starving conditions.

Microglia are highly dynamic cells in the brain. Their functional diversity and phenotypic versatility brought microglial energy metabolism into the focus of research. Although it is known that microenvironmental cues shape microglial phenotype, their bioenergetic response to local nutrient availability remains unclear.

Enhanced detection with spectral imaging fluorescence microscopy reveals tissue- and cell-type-specific compartmentalization of surface-modified polystyrene nanoparticles.

Background: Precisely targeted nanoparticle delivery is critically important for therapeutic applications. However, our knowledge on how the distinct physical and chemical properties of nanoparticles determine tissue penetration through physiological barriers, accumulation in specific cells and tissues, and clearance from selected organs has remained rather limited. In the recent study, spectral imaging fluorescence microscopy was exploited for precise and rapid monitoring of tissue- and cell-type-specific distribution of fluorescent polystyrene nanoparticles with chemically distinct surface compositions.

Differentiation-Dependent Energy Production and Metabolite Utilization: A Comparative Study on Neural Stem Cells, Neurons, and Astrocytes.

While it is evident that the metabolic machinery of stem cells should be fairly different from that of differentiated neurons, the basic energy production pathways in neural stem cells (NSCs) or in neurons are far from clear. Using the model of in vitro neuron production by NE-4C NSCs, this study focused on the metabolic changes taking place during the in vitro neuronal differentiation. O2 consumption, H(+) production, and metabolic responses to single metabolites were measured in cultures of NSCs and in their neuronal derivatives, as well as in primary neuronal and astroglial cultures.

Uptake and bio-reactivity of polystyrene nanoparticles is affected by surface modifications, ageing and LPS adsorption: in vitro studies on neural tissue cells.

Because of their capacity of crossing an intact blood-brain barrier and reaching the brain through an injured barrier or via the nasal epithelium, nanoparticles have been considered as vehicles to deliver drugs and as contrast materials for brain imaging. The potential neurotoxicity of nanoparticles, however, is not fully explored. Using particles with a biologically inert polystyrene core material, we investigated the role of the chemical composition of particle surfaces in the in vitro interaction with different neural cell types.

Dynamics of re-constitution of the human nuclear proteome after cell division is regulated by NLS-adjacent phosphorylation.

Phosphorylation by the cyclin-dependent kinase 1 (Cdk1) adjacent to nuclear localization signals (NLSs) is an important mechanism of regulation of nucleocytoplasmic transport. However, no systematic survey has yet been performed in human cells to analyze this regulatory process, and the corresponding cell-cycle dynamics have not yet been investigated. Here, we focused on the human proteome and found that numerous proteins, previously not identified in this context, are associated with Cdk1-dependent phosphorylation sites adjacent to their NLSs.

Regulation of mouse microglia activation and effector functions by bone marrow-derived mesenchymal stem cells.

Mesenchymal stems or stromal cells (MSCs) are rare multipotent cells with potent regenerative and immunomodulatory properties. Microglial cells (MGs) are specialized tissue macrophages of the central nervous system (CNS) that continuously survey their environment with highly motile extensions. Recently, several studies have shown that MSCs are capable of reprogramming microglia into an "M2-like" phenotype characterized by increased phagocytic activity and upregulated expression of anti-inflammatory mediators in vitro.

Interaction of differently functionalized fluorescent silica nanoparticles with neural stem- and tissue-type cells.

Engineered amorphous silica nanoparticles (SiO2 NPs), due to simple and low cost production, are increasingly used in commercial products and produced on an industrial scale. Despite the potential benefits, there is a concern that exposure to certain types of SiO2 NPs may lead to adverse health effects. As some NPs can cross the blood--brain barrier and may, in addition, reach the central nervous system through the nasal epithelium, this study addresses the responses of different neural tissue-type cells including neural stem cells, neurons, astrocytes and microglia cells to increasing doses of 50 nm fluorescent core/shell SiO2 NPs with different [-NH2, -SH and polyvinylpyrrolidone (PVP)] surface chemistry.

Optical waveguide lightmode spectroscopic techniques for investigating membrane-bound ion channel activities.

Optical waveguide lightmode spectroscopic (OWLS) techniques were probed for monitoring ion permeation through channels incorporated into artificial lipid environment. A novel sensor set-up was developed by depositing liposomes or cell-derived membrane fragments onto hydrophilic polytetrafluoroethylene (PTFE) membrane. The fibrous material of PTFE membrane could entrap lipoid vesicles and the water-filled pores provided environment for the hydrophilic domains of lipid-embedded proteins.

Retinoid machinery in distinct neural stem cell populations with different retinoid responsiveness.

Retinoic acid (RA) is present at sites of neurogenesis in both the embryonic and adult brain. While it is widely accepted that RA signaling is involved in the regulation of neural stem cell differentiation, little is known about vitamin A utilization and biosynthesis of active retinoids in the neurogenic niches, or about the details of retinoid metabolism in neural stem cells and differentiating progenies. Here we provide data on retinoid responsiveness and RA production of distinct neural stem cell/neural progenitor populations.

Isolation of radial glia-like neural stem cells from fetal and adult mouse forebrain via selective adhesion to a novel adhesive peptide-conjugate.

Preferential adhesion of neural stem cells to surfaces covered with a novel synthetic adhesive polypeptide (AK-cyclo[RGDfC]) provided a unique, rapid procedure for isolating radial glia-like cells from both fetal and adult rodent brain. Radial glia-like (RGl) neural stem/progenitor cells grew readily on the peptide-covered surfaces under serum-free culture conditions in the presence of EGF as the only growth factor supplement. Proliferating cells derived either from fetal (E 14.

Lack of neuroprotection in the absence of P2X7 receptors in toxin-induced animal models of Parkinson's disease.

Background: Previous studies indicate a role of P2X7 receptors in processes that lead to neuronal death. The main objective of our study was to examine whether genetic deletion or pharmacological blockade of P2X7 receptors influenced dopaminergic cell death in various models of Parkinson's disease (PD).

Results: mRNA encoding P2X7 and P2X4 receptors was up-regulated after treatment of PC12 cells with 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP).

Neural Stem Cell Spreading on Lipid Based Artificial Cell Surfaces, Characterized by Combined X-ray and Neutron Reflectometry.

We developed a bioadhesive coating based on a synthetic peptide-conjugate (AK-cyclo[RGDfC]) which contains multiples of the arginyl-glycyl-aspartic acid (RGD) amino acid sequence. Biotinylated AK-cyclo[RGDfC] is bound to a supported lipid bilayer via a streptavidin interlayer. Layering, hydration and packing of the coating is quantified by X-ray and neutron reflectometry experiments.

Survival and differentiation of neuroectodermal cells with stem cell properties at different oxygen levels.

Freeze-lesioned regions of the forebrain cortex provide adequate environment for growth of non-differentiated neural progenitors, but do not support their neuron formation. Reduced oxygen supply, among numerous factors, was suspected to impair neuronal cell fate commitment. In the present study, proliferation and differentiation of neural stem/progenitor cells were investigated at different oxygen levels both in vitro and in vivo.

Effects of a combretastatin A4 analogous chalcone and its Pt-complex on cancer cells: A comparative study of uptake, cell cycle and damage to cellular compartments.

The combretastatin A4 analogous chalcone (2E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 1 and its dichloridoplatinum(II) (6-aminomethylnicotinate) complex 2 were previously found to be highly active against a variety of cancer cell lines while differing in their apoptosis induction and long-term regrowth retardation (Schobert et al. [1]). Further differences were identified now.

Translocator protein (TSPO 18kDa) is expressed by neural stem and neuronal precursor cells.

Translocator protein 18 kDa, the peripheral benzodiazepine receptor by its earlier name, is a mitochondrial membrane protein associated with the mitochondrial permeability pore. While the function of the protein is not properly understood, it is known to play roles in necrotic and apoptotic processes of the neural tissue. In the healthy adult brain, TSPO expression is restricted to glial cells.

Astroglia genesis in vitro: distinct effects of retinoic acid in different phases of neural stem cell differentiation.

In the developing CNS, the manifestation of the macro-glial phenotypes is delayed behind the formation of neurons. The "neurons first--glia second" principle seems to be valid for neural tissue differentiation throughout the neuraxis, but the reasons behind are far from clear. In the presented study, the mechanisms of this timing were investigated in vitro, in the course of the neural differentiation of one cell derived NE-4C neuroectodermal stem and P19 embryonic carcinoma cells.

Generation of diverse neuronal subtypes in cloned populations of stem-like cells.

Background: The central nervous tissue contains diverse subtypes of neurons with characteristic morphological and physiological features and different neurotransmitter phenotypes. The generation of neurons with defined neurotransmitter phenotypes seems to be governed by factors differently expressed along the anterior-posterior and dorsal-ventral body axes. The mechanisms of the cell-type determination, however, are poorly understood.

Matrigel-induced acinar differentiation is followed by apoptosis in HSG cells.

It has been shown that a human salivary gland cell line (HSG) is capable of differentiation into gland-like structures, though little is known of how morphological features are formed or controlled. Here we investigated the changes in cell proliferation and apoptosis upon terminal differentiation of HSG cells in Matrigel, an extracellular matrix derivative. Changes in the expression of survivin, a prominent anti-apoptotic factor, and caspase-3, a key apoptotic factor were also measured.

Fibronectin quantification without antibodies: a bioassay for the detection of the gelatin-captured macromolecule.

We have developed a new cell-adhesion-bioassay (CAA) for the quantitative determination of fibronectin in biological fluids. The assay is based on two particular properties of fibronectin: it specifically binds to gelatin with high affinity and simultaneously it can anchor to different surface molecules of a cell. First fibronectin, derived from very different biological fluids, is purified in situ, within the wells of the microtiter plates applied for the assay, using solid surface bound gelatin.

Supersensitivity of P2X receptors in cerebrocortical cell cultures after in vitro ischemia.

Neuronally enriched primary cerebrocortical cultures were exposed to glucose-free medium saturated with argon (in vitro ischemia) instead of oxygen (normoxia). Ischemia did not alter P2X7 receptor mRNA, although serum deprivation clearly increased it. Accordingly, P2X7 receptor immunoreactivity (IR) of microtubuline-associated protein 2 (MAP2)-IR neurons or of glial fibrillary acidic protein (GFAP)-IR astrocytes was not affected; serum deprivation augmented the P2X7 receptor IR only in the astrocytic, but not the neuronal cell population.

Effect of ischemic preconditioning on rat liver microcirculation monitored with laser Doppler flowmetry.

Background: Ischemic preconditioning (IP) may protect the liver from ischemia-reperfusion (I-R) injury during liver resection. This study investigated the effect of IP on hepatic microcirculation (HM) and analyzed the objective parameters of the HM using laser Doppler flowmetry (LDF).

Methods: We used male Wistar rats (250-280 g) that underwent normothermic, segmental liver ischemia.

Studies on the use of NE-4C embryonic neuroectodermal stem cells for targeting brain tumour.

Neural stem cells were suggested to migrate to and invade intracranial gliomas. In the presented studies, interactions of NE-4C embryonic neural stem cells were investigated with C6 and Gl261, LL and U87, glioblastoma cells or with primary astrocytes. Glioma-derived humoral factors did not influence the proliferation of stem cells.