Abstract
Neuropeptides are emerging as key regulators of stem cell niche activities in health and disease, both inside and outside the central nervous system (CNS). Among them, neuropeptide Y (NPY), one of the most abundant neuropeptides both in the nervous system and in non-neural districts, has become the focus of much attention for its involvement in a wide range of physiological and pathological conditions, including the modulation of different stem cell activities. In particular, a pro-neurogenic role of NPY has been evidenced in the neurogenic niche, where a direct effect on neural progenitors has been demonstrated, while different cellular types, including astrocytes, microglia and endothelial cells, also appear to be responsive to the peptide. The marked modulation of the NPY system during several pathological conditions that affect neurogenesis, including stress, seizures and neurodegeneration, further highlights the relevance of this peptide in the regulation of adult neurogenesis. In view of the considerable interest in understanding the mechanisms controlling neural cell fate, this review aims to summarize and discuss current data on NPY signaling in the different cellular components of the neurogenic niche in order to elucidate the complexity of the mechanisms underlying the modulatory properties of this peptide.
Highlights
In adult tissues, stem cells reside in a permissive and specialized microenvironment, or niche, in which different molecular signals coming from the external environment, together with feedback signals from progeny to parent cells, tightly regulate self-renewal, multipotency and stem cell fate
One of the most abundant neuropeptides in the central nervous system (CNS) is neuropeptide Y (NPY), a 36-amino-acid polypeptide that is highly conserved during phylogenesis (Larhammar et al, 1993)
Noggin, which participates in self-renewal processes (Bonaguidi et al, 2008), Sox-2 and Sonic hedgehog, both involved in the establishment and maintenance of the hippocampal niche (Favaro et al, 2009), NeuroD1, which regulates differentiation and maturation processes (Roybon et al, 2009), Doublecortin, a driver of neuroblast migration (Nishimura et al, 2014) and brain-derived neurotrophic factor (BDNF), which is involved in different aspects of dentate neurogenesis (Noble et al, 2011), have all been reported to be significantly modulated within the first 24 h following treatment with NPY (Corvino et al, 2012, 2014)
Summary
Stem cells reside in a permissive and specialized microenvironment, or niche, in which different molecular signals coming from the external environment, together with feedback signals from progeny to parent cells, tightly regulate self-renewal, multipotency and stem cell fate (for review see Hsu and Fuchs, 2012). In this regard, many findings underlie the key role played by neurotransmitters on stem cell biology in niches located both inside and outside the central nervous system (CNS; for review see Katayama et al, 2006; Riquelme et al, 2008). Neuropeptides, molecules released both by neurons, as co-transmitters, and by many additional release sites (for review see van den Pol, 2012), are emerging as important mediators for signaling in both neurogenic and non-neurogenic stem cell niches (for review see Oomen et al, 2000; Louridas et al, 2009; Zaben and Gray, 2013), representing possible shared signaling molecules in their biological dynamics
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