Morphological alterations induced by the exposure to TiO2 nanoparticles in primary cortical neuron cultures and in the brain of rats.

Xavier Valentini,Pascaline Rugira,Annica Frau,Sophie Laurent,Denis Nonclercq,Paula Paci,Laurence Ris,Dimitri Stanicki,Pauline Deneufbourg

doi:10.1016/j.toxrep.2018.08.006

Xavier Valentini, Pascaline Rugira + Show 7 more

Open Access

https://doi.org/10.1016/j.toxrep.2018.08.006

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Journal: Toxicology reports	Publication Date: Jan 1, 2018
Citations: 37	License type: cc-by

Affiliation: University of Mons

Abstract

Nowadays, nanoparticles (NPs) of titanium dioxide (TiO2) are abundantly produced. TiO2 NPs are present in various food products, in paints, cosmetics, sunscreens and toothpastes. However, the toxicity of TiO2 NPs on the central nervous system has been poorly investigated until now. The aim of this study was to evaluate the toxicity of TiO2 NPs on the central nervous system in vitro and in vivo. In cell cultures derived from embryonic cortical brain of rats, a significant decrease in neuroblasts was observed after 24 to 96 h of incubation with TiO2 NPs (5 to 20 μg/ml). This phenomenon resulted from an inhibition of neuroblast proliferation and a concomitant increase in apoptosis. In the same time, a gliosis, characterized by an increase in proliferation of astrocytes and the hypertrophy of microglial cells, occurred. The phagocytosis of TiO2 NPs by microgliocytes was also observed. In vivo, after intraperitoneal injection, the TiO2 NPs reached the brain through the blood brain barrier and the nanoparticles promoted various histological injuries such as cellular lysis, neuronal apoptosis, and inflammation. A reduction of astrocyte population was observed in some brain area such as plexiform zone, cerebellum and subependymal area. An oxidative stress was also detected by immunohistochemistry in neurons of hippocampus, cerebellum and in subependymal area. In conclusion, our study demonstrated clearly the toxic impact of TiO2 NPs on rat brain and neuronal cells and pointed about not yet referenced toxicity impacts of TiO2 such as the reduction of neuroblast proliferation both in vitro and in vivo.

Highlights

IntroductionThe use of nanotechnologies, such as nanoparticles (NPs), has drastically increased in industrial and emerging countries
For several years, the use of nanotechnologies, such as nanoparticles (NPs), has drastically increased in industrial and emerging countries
The average aggregate size of TiO2 NPs was analyzed both by electron microscopy and by dynamic light scattering (DLS), the size of NPs aggregates determined by DLS was 52 ± 15 nm (Fig.1A and B) and the mean size of the nanoparticle aggregates evaluated by electron microscopy was 34 ± 9 nm (Fig. 1C)

Summary

Introduction

The use of nanotechnologies, such as nanoparticles (NPs), has drastically increased in industrial and emerging countries. Inside the class of nanometric compounds, titanium dioxide (TiO2) NPs are one of the most produced. Nearly 6 million tons of TiO2 were produced worldly [1] and the percentage of TiO2 under nanoform was estimated to reach 50% of the total production in the year 2023 [2]. TiO2 NPs are used in a large panel of uses such as cosmetic industry (sunscreens, face powder) [3], battery production, pharmaceutical industry (articulating prosthetic implants, drug coating) [4] and food industry (food coloring) [5]. The raise of utilization of NPs is due to their small size (less than 100 nm), large surface area and high reactivity [6]. Despite the wide ranges of applications, there is a lack of information about the interaction of these NPs with biological systems including the impact of TiO2 exposure on the nervous system at short and long time

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