Local origin and activity-dependent generation of nestin-expressing protoplasmic astrocytes in CA1

Max Delbrück Center for Molecular Medicine (MDC), Berlin-Buch, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Brain Structure and Function (Impact Factor: 5.62). 08/2007; 212(1):19-35. DOI: 10.1007/s00429-007-0141-5
Source: PubMed


Since reports that precursor cells in the adult subventricular zone (SVZ) contribute to regenerative neuro- and gliogenesis in CA1, we wondered whether a similar route of migration might also exist under physiological conditions. Permanent labeling of SVZ precursor cells with a lentiviral vector for green fluorescent protein did not reveal any migration from the SVZ into CA1 in the intact murine brain. However, in a nestin-GFP reporter mouse we found proliferating cells within the corpus callosum/alveus region expressing nestin and glial fibrillary acidic protein similar to precursor cells in the neighboring neurogenic region of the adult dentate gyrus. Within 3 weeks of BrdU administration, BrdU-positive nestin-GFP-expressing protoplasmic astrocytes emerged in CA1. Similar to precursor cells isolated from the dentate gyrus and the SVZ, nestin-GFP-expressing cells from corpus callosum/alveus were self-renewing and multipotent in vitro, whereas cells isolated from CA1 were not. Nestin-GFP-expressing cells in CA1 differentiated into postmitotic astrocytes characterized by S100beta expression. No new neurons were found in CA1. The number of nestin-GFP-expressing astrocytes in CA1 was increased by environmental enrichment. We conclude that astrogenesis in CA1 is influenced by environmental conditions. However, SVZ precursor cells do not contribute to physiological cellular plasticity in CA1.

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    • "But NG2 cells might also express some neuronal markers (along side glial characteristics ), including the expression of doublecortin (DCX), which in the course of adult neurogenesis is expressed by the determined progenitor cells (Type-2b/3 in the SGZ and C and A cells of the SVZ; Ehninger et al., 2011; Guo et al., 2010). Electrophysiologically, NG2 cells show a characteristic ''complex'' pattern, distinct from the passive glial patterns, but also different from neuronal features (Kronenberg et al., 2007; Steinhauser et al., 1992). NG2 cells are found in both neurogenic zones, but their number in the SGZ is very low. "
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    ABSTRACT: Adult neurogenesis is an exceptional feature of the adult brain and in an intriguing way bridges between neuronal and glial neurobiology. Essentially, all classes of glial cells are directly or indirectly linked to this process. Cells with astrocytic features, for example, serve as radial glia-like stem cells in the two neurogenic regions of the adult brain, the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles, producing new neurons, create a microenvironment permissive for neurogenesis, and are themselves generated alongside the new neurons in an associated but independently regulated process. Oligodendrocytes are generated from precursor cells intermingled with those generating neurons in an independent lineage. NG2 cells have certain precursor cell properties and are found throughout the brain parenchyma. They respond to extrinsic stimuli and injury but do not generate neurons even though they can express some preneuronal markers. Microglia have positive and negative regulatory effects as constituents of the "neurogenic niche". Ependymal cells play incompletely understood roles in adult neurogenesis, but under certain conditions might exert (back-up) precursor cell functions. Glial contributions to adult neurogenesis can be direct or indirect and are mediated by mechanisms ranging from gap-junctional to paracrine and endocrine. As the two neurogenic regions differ between each other and both from the non-neurogenic rest of the brain, the question arises in how far regionalization of both the glia-like precursor cells as well as of the glial cells determines site-specific "neurogenic permissiveness." In any case, however, "neurogenesis" appears to be an essentially glial achievement.
    Glia 02/2012; 60(2):159-74. DOI:10.1002/glia.21247 · 6.03 Impact Factor
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    • "However, in the adult rodent brain, DCX expression is not limited to the hippocampus and the subventricular zone/olfactory bulb. DCX-positive cells are found, for example, in the striatum [15], [16], migrating in and below the corpus callosum [17], [18], or in the piriform cortex [19], [20]. Throughout the cortical parenchyma one finds satellite cells positive for proteoglycan NG2, often co-expressing DCX. "
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    ABSTRACT: The piriform cortex receives input from the olfactory bulb and (via the entorhinal cortex) sends efferents to the hippocampus, thereby connecting the two canonical neurogenic regions of the adult rodent brain. Doublecortin (DCX) is a cytoskeleton-associated protein that is expressed transiently in the course of adult neurogenesis. Interestingly, the adult piriform cortex, which is usually considered non-neurogenic (even though some reports exist that state otherwise), also contains an abundant population of DCX-positive cells. We asked how similar these cells would be to DCX-positive cells in the course of adult hippocampal neurogenesis. Using BAC-generated transgenic mice that express GFP under the DCX promoter, we studied DCX-expression and electrophysiological properties of DCX-positive cells in the mouse piriform cortex in comparison with the dentate gyrus. While one class of cells in the piriform cortex indeed showed features similar to newly generated immature granule neurons, the majority of DCX cells in the piriform cortex was mature and revealed large Na+ currents and multiple action potentials. Furthermore, when proliferative activity was assessed, we found that all DCX-expressing cells in the piriform cortex were strictly postmitotic, suggesting that no DCX-positive "neuroblasts" exist here as they do in the dentate gyrus. We conclude that DCX in the piriform cortex marks a unique population of postmitotic neurons with a subpopulation that retains immature characteristics associated with synaptic plasticity. DCX is thus, per se, no marker of neurogenesis but might be associated more broadly with plasticity.
    PLoS ONE 10/2011; 6(10):e25760. DOI:10.1371/journal.pone.0025760 · 3.23 Impact Factor
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    • "In the neocortex, physiological paradigms of behavioral activity, voluntary wheel running, and environmental enrichment, all of which robustly induce adult hippocampal neurogenesis, can additionally induce gliogenesis and the proliferation of resident microglia in the cortex (Ehninger and Kempermann 2003). The same stimuli also induce the proliferation of astrocytes in the non-neurogenic hippocampal area CA1 (Kronenberg et al. 2007). The possible involvement of these behavioral paradigms in the regulation of the de novo cell formation in other brain structures and the physiological relevance of such a regulation remain to be determined. "
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    ABSTRACT: Proliferative cells expressing proteoglycan neuron-glia 2 (NG2) are considered to represent parenchymal precursor cells in the adult brain and are thought to differentiate primarily into oligodendrocytes. We have studied cell genesis in the adult amygdala and found that, up to 1 year after the labeling of proliferating cells with bromodeoxyuridine, most proliferating NG2 cells remain NG2 cells, and only a few slowly differentiate into mature oligodendrocytes, as assessed by the expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase. We have detected no signs of neurogenesis but have confirmed the expression of "neuronal" markers such as Doublecortin in NG2 cells. Nestin-expressing NG2 cells in the amygdala show electrophysiological properties known for oligodendrocyte precursor cells in the corpus callosum. Application of the glutamate agonist kainate elicits a "complex" response consisting of a rapid and long-lasting blockade of the resting K(+) conductance, a transient cationic current, and a transient increase of an outwardly directed K(+) conductance, suggesting the responsiveness of NG2 cells to excitation. Proliferation of NG2 cells increases in response to behavioral stimuli of activity, voluntary wheel running, and environmental enrichment. In addition to reducing the number of newborn microglia, behavioral activity results in a decrease in S100β-expressing newborn NG2 cells in the amygdala. Because S100β expression in NG2 cells ceases with oligodendrocyte maturation, this finding suggests that NG2 cells in the amygdala undergo activity-dependent functional alterations, without resulting in a measurable increase in new mature oligodendrocytes over the time period covered by the present study. The adult amygdala thus shows signs of mixed activity-dependent plasticity: reduced numbers of microglia and, presumably, an altered fate of NG2 cells.
    Cell and Tissue Research 06/2011; 345(1):69-86. DOI:10.1007/s00441-011-1200-z · 3.57 Impact Factor
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