Abstract
BackgroundSilica-ε-polycaprolactone-nanoparticles (SiPCL-NPs) represent a promising tool for laser-tissue soldering in the brain. After release of the SiPCL-NPs in the brain, neuronal differentiation might be modulated. The present study was performed to determine effects of SiPCL-NP-exposure at different stages of neuronal differentiation in neuron-like SH-SY5Y cells. The resulting phenotypes were analyzed quantitatively and signaling pathways involved in neuronal differentiation and degeneration were studied. SH-SY5Y cells were differentiated with all-trans retinoic acid or staurosporine to obtain predominantly cholinergic or dopaminergic neurons. The resulting phenotype was analyzed at the end of differentiation with and without the SiPCL-NPs given at various times during differentiation.ResultsExposure to SiPCL-NPs before and during differentiation led to a decreased cell viability of SH-SY5Y cells depending on the differentiation protocol used. SiPCL-NPs co-localized with the neuronal marker β-3-tubulin but did not alter the morphology of these cells. A significant decrease in the number of tyrosine hydroxylase (TH) immunoreactive neurons was found in staurosporine-differentiated cells when SiPCL-NPs were added at the end of the differentiation. TH-protein expression was also significantly downregulated when SiPCL-NPs were applied in the middle of differentiation. Protein expression of the marker for the dopamine active transporter (DAT) was not affected by SiPCL-NPs. SiPCL-NP-exposure predominantly decreased the expression of the high-affinity choline transporter 1 (CHT1) when the NPs were given before the differentiation. Pathways involved in neuronal differentiation, namely Akt, MAP-K, MAP-2 and the neurodegeneration-related markers β-catenin and GSK-3β were not altered by NP-exposure.ConclusionsThe decrease in the number of dopaminergic and cholinergic cells may implicate neuronal dysfunction, but the data do not provide evidence that pathways relevant for differentiation and related to neurodegeneration are impaired.
Highlights
Silica-ε-polycaprolactone-nanoparticles (SiPCL-NPs) represent a promising tool for laser-tissue solder‐ ing in the brain
SiPCL-NPs at a concentration of 2.6 × 1010 NPs/ml (24.9 μg/ml) significantly decreased the cell viability in all-trans retinoic acid (RA)- and staurosporine (ST)-differentiated SH-SY5Y cells with the effect depending on the specific timing of the exposure and the differentiation-supplement used (Fig. 1a–c)
Cell viability was significantly reduced after SiPCL-NP-incubation at day in vitro (DIV) 1 in undifferentiated, RA-differentiated and ST-treated cells, respectively with the effect being more pronounced in RA-treated cells (Fig. 1a)
Summary
Silica-ε-polycaprolactone-nanoparticles (SiPCL-NPs) represent a promising tool for laser-tissue solder‐ ing in the brain. Intranasal administration of silica nanoparticles (Si-NPs) in rats was reported to induce oxidative stress and apoptosis in the striatum [8] and increase apoptotic cell death in hypothalamic neuronal cells (GT1) [9]. Uptake of SiPCL-NPs designed for laser-tissue soldering [5, 6] has been demonstrated for microglia and neuron-like SH-SY5Y cells. The Wnt/β-catenin-pathway is involved in the development and maintenance of the nervous system [29] Activation of this pathway was reported to prevent neuronal death [17, 30], while a decrease in Wnt-signaling is related to the pathogenesis of neurodegeneration [31, 32]. In line with this notion, titanium dioxide NPs (TiO2NPs) have been demonstrated to significantly decrease the expression of markers of the Wnt-pathway [33]
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