Characterization of superparamagnetic iron oxide nanoparticle-induced apoptosis in PC12 cells and mouse hippocampus and striatum

Liu, Yutong; Li, Juan; Xu, Kaige; Gu, Jingjing; Huang, Lu; Zhang, Lei; Liu, N.; Kong, Jiming; Xing, Malcolm; Zhang, Lin; Zhang, Lu

doi:10.1016/j.toxlet.2018.04.033

Cited by 52 publications

(32 citation statements)

References 38 publications

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“…The particles deposited at concentrations of 0.040 µg/g and 0.050 µg/g in striata and in hippocampi, respectively. More recently, an in vivo investigation showed that rabbit treated with Fe 3 O 4 NPs exhibited the mitochondrial disease and dysfunction with elevated oxidative stress in the brain [18], and another study provides the direct evidence that locally administered SPIONs in the striatum and hippocampus of mice were able to induce both apoptosis and deficits in some behavioral performance [19].…”

Section: Discussionmentioning

confidence: 98%

Neuron-Like Cells Generated from Human Umbilical Cord Lining-Derived Mesenchymal Stem Cells as a New In Vitro Model for Neuronal Toxicity Screening: Using Magnetite Nanoparticles as an Example

Simone

Spinillo

Caloni

et al. 2019

IJMS

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The wide employment of iron nanoparticles in environmental and occupational settings underlines their potential to enter the brain. Human cell-based systems are recommended as relevant models to reduce uncertainty and to improve prediction of human toxicity. This study aimed at demonstrating the in vitro differentiation of the human umbilical cord lining-derived-mesenchymal stem cells (hCL-MSCs) into neuron-like cells (hNLCs) and the benefit of using them as an ideal primary cell source of human origin for the neuronal toxicity of Fe3O4NPs (magnetite-nanoparticles). Neuron-like phenotype was confirmed by: live morphology; Nissl body staining; protein expression of different neuronal-specific markers (immunofluorescent staining), at different maturation stages (i.e., day-3-early and day-8-full differentiated), namely β-tubulin III, MAP-2, enolase (NSE), glial protein, and almost no nestin and SOX-2 expression. Synaptic makers (SYN, GAP43, and PSD95) were also expressed. Fe3O4NPs determined a concentration- and time-dependent reduction of hNLCs viability (by ATP and the Trypan Blue test). Cell density decreased (20–50%) and apoptotic effects were detected at ≥10 μg/mL in both types of differentiated hNLCs. Three-day-differentiated hNLCs were more susceptible (toxicity appeared early and lasted for up to 48 h) than 8-day-differentiated cells (delayed effects). The study demonstrated that (i) hCL-MSCs easily differentiated into neuronal-like cells; (ii) the hNCLs susceptibility to Fe3O4NPs; and (iii) human primary cultures of neurons are new in vitro model for NP evaluation.

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Section: Discussionmentioning

confidence: 98%

Neuron-Like Cells Generated from Human Umbilical Cord Lining-Derived Mesenchymal Stem Cells as a New In Vitro Model for Neuronal Toxicity Screening: Using Magnetite Nanoparticles as an Example

Simone

Spinillo

Caloni

et al. 2019

IJMS

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“…Neurotoxic were also Fe 3 O 4 NPs when administered directly into the dorsal striatum or hippocampus of mice. Fe 3 O 4 NPs administration reduced TH + fiber in both dorsal striatum and hippocampus and caused motor memory deficits, attributed to activation of MAPK and JNK signalling pathways [22].…”

Section: In Vivo Toxicity In Mammalsmentioning

confidence: 99%

“…Metallic NPs can resonate in the magnetic field, thus delivering energy directly to the target cancer cells [20]. Due to the increasing use of metallic NPs in medicine, more and more attention is paid to the safety of using NPs for CNS [22]. Numerous studies indicate inability of blood-brain barrier (BBB) to protect against NPs translocation to the brain [23].…”

Section: Introductionmentioning

confidence: 99%

Toxicity of metallic nanoparticles in the central nervous system

Sawicki

Czajka

Matysiak‐Kucharek

et al. 2019

Nanotechnology Reviews

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Metallic nanoparticles due to their small size and unique physico-chemical characteristics have found excellent applications in various branches of industry and medicine. Therefore, for many years a growing interest has been observed among the scientific community in the improvement of our understanding of the impact of nanoparticles on the living organisms, especially on humans. Considering the delicate structure of the central nervous systemit is one of the organs most vulnerable to the adverse effects of metallic nanoparticles. For that reason, it is important to identify the modes of exposure and understand the mechanisms of the effect of nanoparticles on neuronal tissue. In this review, an attempt is undertaken to present current knowledge about metallic nanoparticles neurotoxicity based on the selected scientific publications. The route of entry of nanoparticles is described, as well as their distribution, penetration through the cell membrane and the blood-brain barrier. In addition, a study on the neurotoxicity in vitro and in vivo is presented, as well as some of the mechanisms that may be responsible for the negative effects of metallic nanoparticles on the central nervous system. Graphical abstract: This review summarizes the current knowledge on the toxicity of metallic NPs in the brain and central nervous system of the higher vertebrates.

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“…Altogether our findings proved that the critical concentrations of Fe 3 O 4 NPs capable to cause in vitro neurotoxicity were similar to those quantified in brain tissue (0.040–58 μg/g) and peripheral blood (350–375 μg/mL) of laboratory animals (i.e., mice, rats, rabbits) treated with IONPs, whose iron content was associated with cytotoxic effects (such as altered mitochondrial function, cell membrane damage, oxidative stress, inflammation, neuronal cell cycle induction resulting in apoptosis), increase of cerebral neurotransmitters content (such as dopamine and norepinephrine), and motor and memory deficits [ 62 , 63 , 64 , 65 , 66 , 67 ].…”

Section: Discussionmentioning

confidence: 99%

Developmental Neurotoxicity Screening for Nanoparticles Using Neuron-Like Cells of Human Umbilical Cord Mesenchymal Stem Cells: Example with Magnetite Nanoparticles

et al. 2020

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Metallic nanoparticles (NPs), as iron oxide NPs, accumulate in organs, cross the blood-brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Human stem cell-derived in vitro models may provide more realistic platforms to study NPs effects on neural cells, and to obtain relevant information on the potential for early or late DNT effects in humans. Primary neuronal-like cells (hNLCs) were generated from mesenchymal stem cells derived from human umbilical cord lining and the effects caused by magnetite (Fe3O4NPs, 1–50 μg/mL) evaluated. Neuronal differentiation process was divided into stages: undifferentiated, early, mid- and fully-differentiated (from day-2 to 8 of induction) based on different neuronal markers and morphological changes over time. Reduction in neuronal differentiation induction after NP exposure was observed associated with NP uptake: β-tubulin III (β-Tub III), microtubule-associated protein 2 (MAP-2), enolase (NSE) and nestin were downregulated (10–40%), starting from 25 μg/mL at the early stage. Effects were exacerbated at higher concentrations and persisted up to 8 days without cell morphology alterations. Adenosine triphosphate (ATP) and caspase-3/7 activity data indicated Fe3O4NPs-induced cell mortality in a concentration-dependent manner and increases of apoptosis: effects appeared early (from day-3), started at low concentrations (≥5 μg/mL) and persisted. This new human cell-based model allows different stages of hNLCs to be cultured, exposed to NPs/chemicals, and analyzed for different endpoints at early or later developmental stage.

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Characterization of superparamagnetic iron oxide nanoparticle-induced apoptosis in PC12 cells and mouse hippocampus and striatum

Cited by 52 publications

References 38 publications

Neuron-Like Cells Generated from Human Umbilical Cord Lining-Derived Mesenchymal Stem Cells as a New In Vitro Model for Neuronal Toxicity Screening: Using Magnetite Nanoparticles as an Example

Neuron-Like Cells Generated from Human Umbilical Cord Lining-Derived Mesenchymal Stem Cells as a New In Vitro Model for Neuronal Toxicity Screening: Using Magnetite Nanoparticles as an Example

Toxicity of metallic nanoparticles in the central nervous system

Developmental Neurotoxicity Screening for Nanoparticles Using Neuron-Like Cells of Human Umbilical Cord Mesenchymal Stem Cells: Example with Magnetite Nanoparticles

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