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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 638 (1991), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 695 (1993), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Notes: Alzheimer's disease (AD) is a debilitating disorder of the central nervous system which may affect up to 50% of the population over the age of 85 years. The etiology of AD is unknown and there is currently no cure for the disease. Well-documented losses in cholinergic and other neurotransmitter systems have provided a focal point for attempting pharmacological interventions in AD to ameliorate some of the cognitive deficits that occur. However, current systemic strategies have met with limited success. An alternative strategy, that has been pursued in animal models of neurodegenerative disease, is to augment neurotransmitter function within the brain through tissue transplantation. Such implants have an advantage over conventional drug therapies in that the cells can be precisely placed within compromised areas of the brain. We have pursued a strategy of designing cells, through the use of molecular biology techniques, to produce neurotrophic factors and neurotransmitters. Recently, we developed a primary fibroblast cell line that was genetically modified to express choline acetyltransferase (ChAT). In vitro, these cells produced and released acetylcholine at levels that varied with the amount of choline in the culture media. When implanted into the hippocampus of rats, the in vivo microdialysis technique revealed that the ChAT-expressing fibroblasts continued to produce and release acetylcholine after grafting. Most importantly, the levels of acetylcholine synthesized by the cells could be regulated by the localized infusion of choline in the vicinity of the grafts. These results confirmed previous work which indicated that engineered fibroblasts provide an effective delivery vehicle of different substances to the brain. While the intracerebral implantation of genetically modified cells will not cure AD, the continuing development of this strategy may ultimately provide a powerful approach for ameliorating the devastating cognitive impairments which are a hallmark of this disease.
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  • 3
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 44 (2004), S. 399-421 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: New cells are continuously generated from immature proliferating cells throughout adulthood in many organs, thereby contributing to the integrity of the tissue under physiological conditions and to repair following injury. In contrast, repair mechanisms in the adult central nervous system (CNS) have long been thought to be very limited. However, recent findings have clearly demonstrated that in restricted areas of the mammalian brain, new functional neurons are constantly generated from neural stem cells throughout life. Moreover, stem cells with the potential to give rise to new neurons reside in many different regions of the adult CNS. These findings raise the possibility that endogenous neural stem cells can be mobilized to replace dying neurons in neurodegenerative diseases. Indeed, recent reports have provided evidence that, in some injury models, limited neuronal replacement occurs in the CNS. Here, we summarize our current understanding of the mechanisms controlling adult neurogenesis and discuss their implications for the development of new strategies for the treatment of neurodegenerative diseases.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 308 (1984), S. 637-639 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] In the first experiment, an aspirative lesion was made uni-laterally in the retrosplenial cortex in 19 adult female Sprague-Dawley rats, as described previously16 (Fig. 1). This lesion exposes the hippocampus posterodorsally, and transects at the same time the dorsal subiculum and the perforant ...
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 4 (1998), S. 555-557 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] A RECENT PAPER by Gould and colleagues describes for the first time the generation of new nerve cells in the brains of adult marmoset monkeys (more specifically in the hippocampal formation of the temporal lobe)1. This finding can be added to a growing list of reports2–5 that together render ...
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 1 (1995), S. 201-203 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Parkinson's disease is characterized by a gradual deterioration of neurons that synthesize the neurotransmitter dopamine within the substantia nigra pars compacta of the brain. The resultant decrease of dopamine-containing fibers within the striatum (see Fig. 1a) is associated with several sensory ...
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 12 (2006), S. 1237-1238 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] In principle, embryonic stem cells can be expanded and then differentiated into most cell lineages of a living organism—making them a virtually unlimited source for cell replacement therapy to treat degenerative disease or traumatic injury. In practice, however, it remains almost an art to ...
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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 12 (2006), S. 1115-1115 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Martin et al. reply: C. Cerdan et al. revisit our finding of contamination of human embryonic stem cells (HESCs) by the nonhuman sialic acid Neu5Gc (ref. 2). Studying 18 random human sera and two HESC lines, they find “no correlation” between HESC Neu5Gc content (studied only in a ...
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature America Inc.
    Nature biotechnology 18 (2000), S. 381-382 
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] The establishment of immortal, pluripotent stem cell lines has given rise to a powerful tool for in vitro research of developmental processes at both cellular and organismal levels. These cells also offer tremendous potential for clinical application, serving as an unlimited source of cells for ...
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  • 10
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 7 (2001), S. 393-395 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Stem cells are defined as clonogenic, self-renewing progenitor cells that can generate one or more specialized cell types. In vertebrates, stem cells have been traditionally subdivided into two groups (Fig. 1). The first group consists only of embryonic stem (ES) cells. These pluripotent stem ...
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