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  • 1
    Electronic Resource
    Electronic Resource
    Rotenone-induced caspase 9/3-independent and -dependent cell death in undifferentiated and differentiated human neural stem cells (2005)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 92 (2005), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We used human neural stem cells (hNSCs) and their differentiated cultures as a model system to evaluate the mechanism(s) involved in rotenone (RO)- and camptothecin (CA)-induced cytotoxicity. Results from ultrastructural damage and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining indicated that RO-induced cytotoxicity resembled CA-induced apoptosis more than H2O2-induced necrosis. However, unlike CA-induced, caspase 9/3-dependent apoptosis, there was no increased activity in caspase 9, caspase 3 or poly (ADP-ribose) polymerase (PARP) cleavage in RO-induced cytotoxicity, in spite of time-dependent release of cytochrome c and apoptosis-inducing factor (AIF) following mitochondrial membrane depolarization and a significant increase in reactive oxygen species generation. Equal doses of RO and CA used in hNSCs induced caspase 9/3-dependent apoptosis in differentiated cultures. Time-dependent ATP depletion occurred earlier and to a greater extent in RO-treated hNSCs than in CA-treated hNSCs, or differentiated cultures treated with RO or CA. In conclusion, these results represent a unique ultrastructural and molecular characterization of RO- and CA-induced cytotoxicity in hNSCs and their differentiated cultures. Intracellular ATP levels may play an important role in determining whether neural progenitors or their differentiated cells follow a caspase 9/3-dependent or -independent pathway in response to acute insults from neuronal toxicants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.2004.02872.x
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  • 2
    Electronic Resource
    Electronic Resource
    Gene expression in human neural stem cells: effects of leukemia inhibitory factor (2003)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 86 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Human neural precursor cells grown in culture provide a source of tissue for drug screening, developmental studies and cell therapy. However, mechanisms underlying their growth and differentiation are poorly understood. We show that epidermal growth factor (EGF) responsive precursors derived from the developing human cortex undergo senescence after 30–40 population doublings. Leukemia inhibitory factor (LIF) increased overall expansion rates, prevented senescence and allowed the growth of a long-term self renewing neural stem cell (ltNSCctx) for up to 110 population doublings. We established basal gene expression in ltNSCctx using Affymetrix oligonucleotide microarrays that delineated specific members of important growth factor and signaling families consistently expressed across three separate lines. Following LIF withdrawal, 200 genes showed significant decreases. Protein analysis confirmed LIF-regulated expression of glial fibrillary acidic protein, CD44, and major histocompatibility complex I. This study provides the first molecular profile of human ltNSCctx cultures capable of long-term self renewal, and reveals specific sets of genes that are directly or indirectly regulated by LIF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.01826.x
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  • 3
    Electronic Resource
    Electronic Resource
    5-Bromo-2′-deoxyuridine is selectively toxic to neuronal precursors in vitro (2005)
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 22 (2005), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effect of 5-bromo-2′-deoxyuridine (BrdU) incorporation on the phenotype of progeny derived from expanded E18 rat striatal precursors was examined. BrdU was administered to cultures for 24 h prior to differentiation. Results revealed that there was selective toxicity of this compound to developing TuJ1+ neurons, but not glia, at concentrations used in most labelling studies. Therefore, a BrdU dose–response curve from 0.2 µm to 10 µm was established. The optimum dose of BrdU for labelling cells was 0.2 µm, well below the 1–10 µm recommended concentration. This dose resulted in the survival of significantly more newborn BrdU/TuJ1+ double-labelled neurons and eliminated the toxic effects of BrdU. Administration of 10 µm BrdU resulted in a significant decrease in extracellular regulated kinase (ERK) phosphorylation compared with untreated cultures, this could be completely restored by the administration of either N-methyl-d-aspartate (NMDA) receptor antagonists such as MK801 or the nitric oxide synthesis inhibitor l-methyl-arginine methyl ester (L-NAME). Our results show that high levels of BrdU are selectively toxic to neurons through a mechanism that activates classical cell death pathways. This has implications for labelling studies both in vivo and in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2005.04504.x
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  • 4
    Electronic Resource
    Electronic Resource
    HPLC with electrochemical detection to measure chlorpromazine, thioridazine and metabolites in human brain (1986)
    Springer
    Psychopharmacology 90 (1986), S. 316-321 
    Details
    ISSN: 1432-2072
    Keywords: Chlorpromazine ; Thioridazine ; Metabolites ; High performance liquid chromatography ; Electrochemical detection ; Human brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirteen phenothiazine compounds were separated chromatographically using high performance liquid chromatography with coulometric electrochemical detection. These could be extracted from brain tissue using direct homogenization in tetrahydrofuran followed by one centrifugation, evaporation of supernatant and reconstitution in water. Fluphenazine was used as the internal standard. The absolute lower limit of detection was approximately 50 pg/mg wet tissue, and recovery rates for most standards added to brain homogenates were greater than 85%. Chromatograms from patients receiving chlorpromazine (600 mg) and thioridazine (600 mg) are shown and endogenous brain levels quantified. The results are discussed with respect to their relevance in schizophrenic research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00179183
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  • 5
    Electronic Resource
    Electronic Resource
    Stem cells for Parkinson disease and ALS: replacement or protection? (2004)
    [s.l.] : Nature Publishing Group
    Nature medicine 10 (2004), S. 224-225 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Stem cells are able to both self-renew and produce differentiated tissues. They offer real hope for tissue replacement in a wide range of diseases. Brain repair has been a particular focus of attention because cells transplanted into the nervous system are somewhat immune privileged, reducing the ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm0304-224
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    Growth factors regulate the survival and fate of cells derived from human neurospheres (2001)
    [s.l.] : Nature Publishing Group
    Nature biotechnology 19 (2001), S. 475-479 
    Details
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] Cells isolated from the embryonic, neonatal, and adult rodent central nervous system divide in response to epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2), while retaining the ability to differentiate into neurons and glia. These cultures can be grown in aggregates termed ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/88158
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  • 7
    Electronic Resource
    Electronic Resource
    Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease (2003)
    [s.l.] : Nature Publishing Group
    Nature medicine 9 (2003), S. 589-595 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Glial cell line–derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm850
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  • 8
    Electronic Resource
    Electronic Resource
    Neurobiology The amazing astrocyte (2002)
    [s.l.] : Nature Publishing Group
    Nature 417 (2002), S. 29-32 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The cells that make up our brains come in two main flavours: neurons and glia. Neurons conduct action potentials and have traditionally held centre stage in neurobiological research. By contrast, glia have often been seen as the poor relatives. With their name originating from the Greek word for ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/417029a
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