Morphological alterations induced by the exposure to TiO2 nanoparticles in primary cortical neuron cultures and in the brain of rats. (2018)

• Record Type: Journal Article
• Authors: Valentini, Xavier; Deneufbourg, Pauline; Paci, Paula; Rugira, Pascaline; Laurent, Sophie; Frau, Annica; Stanicki, Dimitri; Ris, Laurence; Nonclercq, Denis
• Is Part Of: Toxicology reports. Volume 5(2018)
• Page Start: 878
• Page End: 889
• Publication Date: 2018
• Subjects: NPs nanoparticles -- BBB blood-brain barrier -- ROS reactive oxygen species -- MDA malondialdehyde -- NO nitric oxide -- IL-1β interleukin-1β -- TNF-α tumor necrosis factor-α -- IL-10 interleukin-10 -- IP intraperitoneal -- DLS dynamic light scattering -- HBSS Hank's balanced salt solution -- FBS fetal bovine serum -- BrdU 5-Bromo-2′-deoxyuridine -- SEM standard error of the mean -- MAP2 microtubule-associated protein 2 -- GFAP glial fibrillary acidic protein -- 4-HNE 4-hydroxynonenal -- NMDA N-methyl-D-aspartate -- NOS nitric oxide synthase -- ATP adenosine triphosphate -- CNS central nervous system; Nanoparticles -- Brain -- Cell culture -- Oxidative stress -- Proliferation; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2018.08.006
• Languages: English
• ISSNs: 2214-7500

Abstract

Graphical abstract: Highlights: The NPs reach the CNS via the blood-brain barrier and cause inflammation and necrotic area in the white matter. Proliferation of glial cells and neuroblasts is affected in vitro and in vivo . An oxidative stress was evidenced in vivo in neurons of hippocampus, cerebellum and in subependymal area. 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 .