Signaling in adult neurogenesis: From stem cell niche to neuronal networks

Technische Universität München, München, Bavaria, Germany
Current Opinion in Neurobiology (Impact Factor: 6.63). 07/2007; 17(3):338-44. DOI: 10.1016/j.conb.2007.04.006
Source: PubMed


The mechanisms that determine why neurogenesis is restricted to few regions of the adult brain in mammals, in contrast to its more widespread nature in other vertebrates such as zebrafish, remain to be fully understood. The local environment must provide key signals that instruct stem cell and neurogenic fate, because non-neurogenic progenitors can be instructed towards neurogenesis in this environment. Here, we discuss the recent progress in understanding key factors in the local stem cell niche of the adult mammalian brain, including surprising sources of new signals such as endothelial cells, complement factors and microglia. Moreover, new insights have been gained into how neuronal diversity is instructed in adult neurogenesis, prompting a new view of stem and progenitor cell heterogeneity in the adult mammalian brain.

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    • "Adult neurogenesis was first characterized in rodents in the 1960s (Altman 1969; Altman and Das 1965), with further attention in the 1990s from a reproductive perspective in song birds (Alvarez-Buylla 1992; Goldman and Nottebohm 1983). Since then, the idea of new neuron formation in adulthood has been widely accepted and in rodents, the dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ) have been regarded as the most prominent neurogenic niches in adulthood (Christian et al. 2014; Lepousez et al. 2013; Ninkovic and Gotz 2007; Rakic 2002; Suh et al. 2009). The hippocampal neurogenesis is found to be important for a series of hippocampus-dependent cognitive functions (Clelland et al. 2009; Sahay et al. 2011), as well as emotional regulation responses of antidepressants (Sahay and Hen 2007), while the SVZ-generated neurons migrate to the olfactory bulb through the rostral migratory stream (RMS). "
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    ABSTRACT: Adult neurogenesis in rodents has been extensively studied. Here we briefly summarized the studies of adult neurogenesis based on non-human primates and human postmortem brain samples. The differences between rodent, primate and human neurogenesis were discussed.
    Cell and Tissue Research 10/2014; 358(1). DOI:10.1007/s00441-014-1980-z · 3.57 Impact Factor
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    • "In addition to systemic effects, NSCs proliferation can also be influenced by cellular and molecular changes taking place within the neurogenic niche (Figure 2). In fact, not only some of the factors mentioned above but also a long list of other signaling molecules and transcription factors known to regulate neurogenesis are produced locally by NSCs, astrocytes, or endothelial cells such as Notch, Wnt, BMP, Shh and several others [123-125]. Unfortunately, in the aging brain most of these factors were not investigated but it is interesting to notice that most, if not all, have been shown to inhibit differentiation and, in addition, shorten the cell cycle of NSCs [126-129]. Since the age-related reduction in NSCs proliferation is known to correlate with reduced levels of growth factors [89, 90], it would not come as a surprise if expression of genes regulating cell cycle length (or quiescence) should also be altered in the aging brain. "
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    ABSTRACT: Several studies suggest that an increase in adult neurogenesis has beneficial effects on emotional behavior and cognitive performance including learning and memory. The observation that aging has a negative effect on the proliferation of neural stem cells has prompted several laboratories to investigate new systems to artificially increase neurogenesis in senescent animals as a means to compensate for age-related cognitive decline. In this review we will discuss the systemic, cellular, and molecular changes induced by aging and affecting the neurogenic niche at the level of neural stem cell proliferation, their fate change, neuronal survival, and subsequent integration in the neuronal circuitry. Particular attention will be given to those manipulations that increase neurogenesis in the aged brain as a potential avenue towards therapy.
    Aging 03/2012; 4(3):176-86. · 6.43 Impact Factor
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    • ", 2006 ; Grandel et al . , 2006 ; Ninkovic and Götz , 2007 ; Pelegrini et al . , 2007 ; Kaslin et al . "
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    ABSTRACT: Adult neurogenesis is a widespread trait of vertebrates; however, the degree of this ability and the underlying activity of the adult neural stem cells differ vastly among species. In contrast to mammals that have limited neurogenesis in their adult brains,zebrafish can constitutively produce new neurons along the whole rostrocaudal brain axis throughout its life.This feature of adult zebrafish brain relies on the presence of stem/progenitor cells that continuously proliferate,and the permissive environment of zebrafish brain for neurogenesis. Zebrafish has also an extensive regenerative capacity, which manifests itself in responding to central nervous system injuries by producing new neurons to replenish the lost ones. This ability makes zebrafish a useful model organism for understanding the stem cell activity in the brain, and the molecular programs required for central nervous system regeneration.In this review, we will discuss the current knowledge on the stem cell niches, the characteristics of the stem/progenitor cells, how they are regulated and their involvement in the regeneration response of the adult zebrafish brain. We will also emphasize the open questions that may help guide the future research.
    Developmental Neurobiology 03/2012; 72(3):429-61. DOI:10.1002/dneu.20918 · 3.37 Impact Factor
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