Review
doi: 10.1007/s00018-015-2067-z. Epub 2015 Oct 14.Effects of addictive drugs on adult neural stem/progenitor cells
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- PMID:26468052
- PMCID: PMC4833708
- DOI: 10.1007/s00018-015-2067-z
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Review
Effects of addictive drugs on adult neural stem/progenitor cells
Chi Xu et al. Cell Mol Life Sci.2016 Jan.
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Abstract
Neural stem/progenitor cells (NSPCs) undergo a series of developmental processes before giving rise to newborn neurons, astrocytes and oligodendrocytes in adult neurogenesis. During the past decade, the role of NSPCs has been highlighted by studies on adult neurogenesis modulated by addictive drugs. It has been proven that these drugs regulate the proliferation, differentiation and survival of adult NSPCs in different manners, which results in the varying consequences of adult neurogenesis. The effects of addictive drugs on NSPCs are exerted via a variety of different mechanisms and pathways, which interact with one another and contribute to the complexity of NSPC regulation. Here, we review the effects of different addictive drugs on NSPCs, and the related experimental methods and paradigms. We also discuss the current understanding of major signaling molecules, especially the putative common mechanisms, underlying such effects. Finally, we review the future directions of research in this area.
Keywords: Addictive drugs; Adult neurogenesis; Differentiation; Neural stem/progenitor cells; Proliferation; Survival.
Figures
Crosstalk between the different mechanisms underlying the modulation of NSPCs. The mechanisms by which morphine, cocaine and methamphetamine (METH) modulate adult NSPCs exemplify the crosstalk between the MAPK cascade, cell cycle regulation and miRNA expression induced by addictive drugs. Morphine up-regulates miR-181a by the ERK/TRBP/Dicer pathway. MiR-181a further controls Prox1/Notch1 signaling, which ultimately results in alterations of NSPC differentiation. Cocaine activates the miR-9/TLX loop, which in turn regulates p21 and further interferes with the effects of cell cycle regulatory molecules that alter proliferation and differentiation of NSPCs. On the other hand, cocaine up-regulates miR-124, which inhibits Notch1 expression, which results in cell cycle arrest. Methamphetamine activates the p53/p21 cascade, which blocks the effects of cell cycle regulatory molecules, resulting in the decreased proliferation and increased neuronal differentiation of NSPCs
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