Effects of silica nanoparticle exposure on mitochondrial function during neuronal differentiation

Ducray, Angélique; Felser, Andrea Debora; Zielinski, Jana; Bittner, Aniela; Bürgi, Julia Verena; Nuoffer, Jean-Marc; Frenz, Martin; Mevissen, Meike (2017). Effects of silica nanoparticle exposure on mitochondrial function during neuronal differentiation. Journal of nanobiotechnology, 15(1), p. 49. BioMed Central 10.1186/s12951-017-0284-3

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BACKGROUND: Nanomedicine offers a promising tool for therapies of brain diseases, but potential effects on neuronal health and neuronal differentiation need to be investigated to assess potential risks. The aim of this study was to investigate effects of silica-indocyanine green/poly (ε-caprolactone) nanoparticles (PCL-NPs) engineered for laser tissue soldering in the brain before and during differentiation of SH-SY5Y cells. Considering adaptations in mitochondrial homeostasis during neuronal differentiation, metabolic effects of PCL-NP exposure before and during neuronal differentiation were studied. In addition, kinases of the PI3 kinase (PI3-K/Akt) and the MAP kinase (MAP-K/ERK) pathways related to neuronal differentiation and mitochondrial function were investigated. RESULTS: Differentiation resulted in a decrease in the cellular respiration rate and the extracellular acidification rate (ECAR). PCL-NP exposure impaired mitochondrial function depending on the time of exposure. The cellular respiration rate was significantly reduced compared to differentiated controls when PCL-NPs were given before differentiation. The shift in ECAR was less pronounced in PCL-NP exposure during differentiation. Differentiation and PCL-NP exposure had no effect on expression levels and the enzymatic activity of respiratory chain complexes. The activity of the glycolytic enzyme phosphofructokinase was significantly reduced after differentiation with the effect being more pronounced after PCL-NP exposure before differentiation. The increase in mitochondrial membrane potential observed after differentiation was not found in SH-SY5Y cells exposed to PCL-NPs before differentiation. The cellular adenosine triphosphate (ATP) production significantly dropped during differentiation, and this effect was independent of the PCL-NP exposure. Differentiation and nanoparticle exposure had no effect on superoxide levels at the endpoint of the experiments. A slight decrease in the expression of the neuronal differentiation markers was found after PCL-NP exposure, but no morphological variation was observed. CONCLUSIONS: PCL-NP exposure affects mitochondrial function depending on the time of exposure before and during neuronal differentiation. PCL-NP exposure during differentiation was associated with impaired mitochondrial function, which may affect differentiation. Considering the importance of adaptations in cellular respiration for neuronal differentiation and function, further studies are needed to unravel the underlying mechanisms and consequences to assess the possible risks including neurodegeneration.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > NeuroCenter
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
08 Faculty of Science > Institute of Applied Physics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Pharmacology and Toxicology

UniBE Contributor:

Ducray, Angélique; Felser, Andrea Debora; Zielinski, Jana; Bittner, Aniela; Bürgi, Julia Verena; Nuoffer, Jean-Marc; Frenz, Martin and Mevissen, Meike

Subjects:

600 Technology > 630 Agriculture
600 Technology > 620 Engineering
600 Technology > 610 Medicine & health

ISSN:

1477-3155

Publisher:

BioMed Central

Language:

English

Submitter:

Jean-Marc Nuoffer

Date Deposited:

08 Mar 2018 09:55

Last Modified:

27 Apr 2018 13:51

Publisher DOI:

10.1186/s12951-017-0284-3

PubMed ID:

28676089

BORIS DOI:

10.7892/boris.110095

URI:

https://boris.unibe.ch/id/eprint/110095

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