Wiedmer, Linda; Ducray, Angélique; Frenz, Martin; Stoffel, Michael Hubert; Widmer, Hans Rudolf; Mevissen, Meike (2019). Silica nanoparticle-exposure during neuronal differentiation modulates dopaminergic and cholinergic phenotypes in SH-SY5Y cells. Journal of nanobiotechnology, 17(1), p. 46. BioMed Central 10.1186/s12951-019-0482-2
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Background:Silica‑ε‑polycaprolactone‑nanoparticles (SiPCL‑NPs) represent a promising tool for laser‑tissue solder‑ing 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.Results:Exposure 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) immunore‑active neurons was found in staurosporine‑differentiated cells when SiPCL‑NPs were added at the end of the differ‑entiation. 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.Conclusions:The decrease in the number of dopaminergic and cholinergic cells may implicate neuronal dysfunc‑tion, but the data do not provide evidence that pathways relevant for differentiation and related to neurodegenera‑tion are impaired.
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