title: Uptake of silica nanoparticles in the brain and effects on neuronal differentiation using different in vitro models.
abstract: Nanomedicine offers a promising tool for therapies of brain diseases, but they may be associated with potential adverse effects. The aim of this study was to investigate the uptake of silica-nanoparticles engineered for laser-tissue soldering in the brain using SH-SY5Y cells, dissociated and organotypic slice cultures from rat hippocampus. Nanoparticles were predominantly taken up by microglial cells in the hippocampal cultures but nanoparticles were also found in differentiated SH-SY5Y cells. The uptake was time- and concentration-dependent in primary hippocampal cells. Transmission electron microscopy experiments demonstrated nanoparticle aggregates and single particles in the cytoplasm. Nanoparticles were found in the endoplasmic reticulum, but not in other cellular compartments. Nanoparticle exposure did not impair cell viability and neuroinflammation in primary hippocampal cultures at all times investigated. Neurite outgrowth was not significantly altered in SH-SY5Y cells, but the neuronal differentiation markers indicated a reduction in neuronal differentiation induction after nanoparticle exposure.
authors.affiliation: Division of Pharmacology and Toxicology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Angélique D
authors.initials: AD
authors.lastname: Ducray
authors.affiliation: Division of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Ana
authors.initials: A
authors.lastname: Stojiljkovic
authors.affiliation: Division of Pharmacology and Toxicology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Möller
authors.affiliation: Division of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Stoffel
authors.affiliation: Department of Neurosurgery, Research Unit, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Widmer
authors.affiliation: Institute of Applied Physics, University of Bern, Bern, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Frenz
authors.affiliation: Division of Pharmacology and Toxicology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. Electronic address: meike.mevissen@vetsuisse.unibe.ch.
authors.forename: Meike
authors.initials: M
authors.lastname: Mevissen
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D012822:Silicon Dioxide
keywords: Nanomedicine; Nanoparticle uptake; Neurodifferentiation; Neuroinflammation