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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Neural cell adhesion molecule (NCAM) influences proliferation and differentiation of neuronal cells. However, only a little is known about the downstream effects of NCAM signalling, such as alterations in gene transcription, which are associated with cell fate choice. To examine whether NCAM plays a role in cell fate choice during hippocampal neurogenesis, we performed a gain-of-function study, using a retroviral vector which contained full-length NCAM140 cDNA and the marker gene EGFP, and found that NCAM140 promoted neurogenesis by activating proneural transcription activators with concurrent inhibition of gliogenesis. The enhanced transcript levels of proneural transcription factors in NCAM140-transduced cells were down-regulated by treatment of the cells with mitogen-activated protein kinase kinase (MEK) inhibitor PD098059. Overall, these findings suggest that NCAM140 may facilitate hippocampal neurogenesis via regulation of proneurogenic transcription factors in an extracellular signal-regulated kinase (ERK)-dependent manner.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Lithium has been demonstrated to increase neurogenesis in the dentate gyrus of rodent hippocampus. The present study was undertaken to investigate the effects of lithium on the proliferation and differentiation of rat neural progenitor cells in hippocampus both in vitro and in vivo. Lithium chloride (1–3 mm) produced a significant increase in the number of bromodeoxyuridine (BrdU)-positive cells in high-density cultures, but did not increase clonal size in low-density cultures. Lithium chloride at 1 mm (within the therapeutic range) also increased the number of cells double-labeled with BrdU antibody and TuJ1 (a class III β-tubulin antibody) in high-density cultures and the number of TuJ1-positive cells in a clone of low-density cultures, whereas it decreased the number of glial fibrillary acidic protein-positive cells in both cultures. These results suggest that lithium selectively increased differentiation of neuronal progenitors. These actions of lithium appeared to enhance a neuronal subtype, calbindinD28k-positive cells, and involved a phosphorylated extracellular signal-regulated kinase and phosphorylated cyclic AMP response element-binding protein-dependent pathway both in vitro and in vivo. These findings suggest that lithium in therapeutic amounts may elicit its beneficial effects via facilitation of neural progenitor differentiation toward a calbindinD28k-positive neuronal cell type.
    Type of Medium: Electronic Resource
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