2011
DOI: 10.1096/fj.11-184697
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Abstract: The mammalian brain contains neural stem cells (NSCs) that enable continued neurogenesis throughout adulthood. However, NSC function and/or numbers decline with increasing age. Adult hippocampal neurogenesis is unique in that astrocytes secreting Wnt3 promote NSC differentiation in a paracrine manner. Here, we show that both the levels of Wnt3 protein and the number of Wnt3-secreting astrocytes influence the impairment of adult neurogenesis during aging. The age-associated reduction in Wnt3 levels affects the … Show more

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Cited by 137 publications
(145 citation statements)
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References 43 publications
(83 reference statements)
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“…Differentiation into the astrocyte lineage was stimulated by the addition of 50 ng/mL leukemia inhibitory factor (LIF) and 50 ng/mL bone morphogenetic protein 2 (BMP2). Astrocytes prepared in vitro expressed Wnt3 factors, consistent with in vivo data (Lie et al, 2005;Kuwabara et al, 2009;Okamoto et al, 2011).…”
Section: Wwwintechopencomsupporting
confidence: 82%
“…Differentiation into the astrocyte lineage was stimulated by the addition of 50 ng/mL leukemia inhibitory factor (LIF) and 50 ng/mL bone morphogenetic protein 2 (BMP2). Astrocytes prepared in vitro expressed Wnt3 factors, consistent with in vivo data (Lie et al, 2005;Kuwabara et al, 2009;Okamoto et al, 2011).…”
Section: Wwwintechopencomsupporting
confidence: 82%
“…Unlike other stem cells, however, the in vitro function of aged NSCs on a per-cell basis is not substantially impaired with age (Ahlenius et al, 2009), which implies that cell-extrinsic factors are largely at play. Indeed, heterochronic parabiosis (the joining of the circulatory systems of two animals of different age) and restoring the levels of IGF-1, GH, Wnt3, TGF-β or GDF11 in old mice to those found in young mice improves neurogenesis (Blackmore et al, 2009;Katsimpardi et al, 2014;Lichtenwalner et al, 2001;Okamoto et al, 2011;Pineda et al, 2013;Villeda et al, 2014). An age-dependent change in the senescence of NSCs also contributes to their declining numbers (Molofsky et al, 2006;Nishino et al, 2008) and might underlie learning and memory deficits in the elderly (Zhao et al, 2008a).…”
Section: Neural Stem Cellsmentioning
confidence: 99%
“…Increasing evidence supports the idea that, during aging, WNT signaling has an instructive role in neuronal fate determination from neural progenitors (2). For example, WNT3 expression decreases during aging (3), while levels of the WNT antagonist Dickkopf 1 (DKK1) increase specifically in the hippocampus (4). It remains unclear whether WNT plays any role in the SVZ; if it does, the mechanism for its regulation during aging is largely unknown.…”
Section: Introductionmentioning
confidence: 99%