Article

Astroglia genesis in vitro: distinct effects of retinoic acid in different phases of neural stem cell differentiation.

Institute of Experimental Medicine of Hungarian Academy of Sciences, Budapest, Hungary.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience (Impact Factor: 2.03). 07/2009; 27(4):365-75. DOI: 10.1016/j.ijdevneu.2009.02.004
Source: PubMed

ABSTRACT In the developing CNS, the manifestation of the macro-glial phenotypes is delayed behind the formation of neurons. The "neurons first--glia second" principle seems to be valid for neural tissue differentiation throughout the neuraxis, but the reasons behind are far from clear. In the presented study, the mechanisms of this timing were investigated in vitro, in the course of the neural differentiation of one cell derived NE-4C neuroectodermal stem and P19 embryonic carcinoma cells. The data demonstrated that astrocyte formation coincided in time with the maturation of postmitotic neurons, but the close vicinity of neurons did not initiate astrocyte formation before schedule. All-trans retinoic acid, a well-known inducer of neuronal differentiation, on the other hand, blocked effectively the astroglia production if present in defined stages of the in vitro neuroectodermal cell differentiation. According to the data, retinoic acid plays at least a dual role in astrogliogenesis: while it is needed for committing neural progenitors for a future production of astrocytes, it prevents premature astrogliogenesis by inhibiting the differentiation of primed glial progenitors.

0 Bookmarks
 · 
59 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Engineered amorphous silica nanoparticles (SiO2 NPs), due to simple and low cost production, are increasingly used in commercial products and produced on an industrial scale. Despite the potential benefits, there is a concern that exposure to certain types of SiO2 NPs may lead to adverse health effects. As some NPs can cross the blood--brain barrier and may, in addition, reach the central nervous system through the nasal epithelium, this study addresses the responses of different neural tissue-type cells including neural stem cells, neurons, astrocytes and microglia cells to increasing doses of 50 nm fluorescent core/shell SiO2 NPs with different [-NH2, -SH and polyvinylpyrrolidone (PVP)] surface chemistry. The SiO2 NPs are characterized using a variety of physicochemical methods. Assays of cytotoxicity and cellular metabolism indicates that SiO2 NPs cause cell death only at high particle doses, except PVP-coated SiO2 NPs which do not harm cells even at very high concentrations. All SiO2 NPs, except those coated with PVP, form large agglomerates in physiological solutions and adsorb a variety of proteins. Except PVP-NPs, all SiO2 NPs adhere strongly to cell surfaces, but internalization differs depending on neural cell type. Neural stem cells and astrocytes internalize plain SiO2, SiO2-NH2 and SiO2-SH NPs, while neurons do not take up any NPs. The data indicates that the PVP coat, by lowering the particle-biomolecular component interactions, reduces the biological effects of SiO2 NPs on the investigated neural cells.
    Nanotoxicology 12/2013; · 7.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Retinoic acid (RA) is present at sites of neurogenesis in both the embryonic and adult brain. While it is widely accepted that RA signaling is involved in the regulation of neural stem cell differentiation, little is known about vitamin A utilization and biosynthesis of active retinoids in the neurogenic niches, or about the details of retinoid metabolism in neural stem cells and differentiating progenies. Here we provide data on retinoid responsiveness and RA production of distinct neural stem cell/neural progenitor populations. In addition, we demonstrate differentiation-related changes in the expression of genes encoding proteins of the retinoid machinery, including components responsible for uptake (Stra6) and storage (Lrat) of vitamin A, transport of retinoids (Rbp4, CrbpI, CrabpI-II), synthesis (Rdh10, Raldh1-4), degradation of RA (Cyp26a1-c1) and RA signaling (Rarα,β,γ; Rxrα,β,γ). We show that both early embryonic neuroectodermal (NE-4C) stem cells and late embryonic or adult derived radial glia like progenitors (RGl cells) are capable to produce bioactive retinoids but respond differently to retinoid signals. However, while neuronal differentiation of RGl cells can not be induced by RA, neuron formation by NE-4C cells is initiated by both RA and RA-precursors (retinol or retinyl acetate). The data indicate that endogenous RA production, at least in some neural stem cell populations, may result in autocrine regulation of neuronal differentiation.
    Stem cells and development 06/2013; · 4.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neurotrophic factors can promote the proliferation and differentiation of neural stem cells (NSCs). Here we report that the possibility of using bFGF in combination with BDNF and NGF to promote proliferation and differentiation of NSCs in vitro. C57BL/6 mouse NSCs were cultured, passaged and stained by immunofluorescence for nestin and GFP. According to different neurotrophic factors added to NSCs, seven experiment groups (NGF, BDNF, bFGF, bFGF+NGF, bFGF+BDNF, NGF+BDNF and NGF+BDNF+bFGF) and a blank control group were established. One week after induction and differentiation, results showed that there was significant difference in the percentage of NSCs differentiating into neurons among the experiment groups. The percentage in the multi-factor groups was significantly higher than that in the single-factor groups (p<0.05), among which the percentage was the highest in NGF+BDNF+bFGF group. In the two-factor groups, the percentage in bFGF+NGF and bFGF+BDNF groups was significantly higher than that in NGF+BDNF group (p< 0.05). The NSCs growth curves showed that cells proliferated continuously with the time of culture prolonging, but there was significant difference between the group containing bFGF and that without bFGF. Our results demonstrate that combined use of NGF/BDNF/bFGF significantly improved the ability of NSCs proliferation and differentiation.
    International Journal of Developmental Neuroscience. 08/2014;

Full-text

Download
11 Downloads
Available from
May 20, 2014