Brain Inflammation, Blood Brain Barrier dysfunction and Neuronal Synaptophysin Decrease after Inhalation Exposure to Titanium Dioxide Nano-aerosol in Aging Rats

Disdier, Clémence; Chalansonnet, Monique; Gagnaire, François; Gaté, Laurent; Cosnier, Frédéric; Devoy, Jérôme; Saba, Wadad; Lund, Amie K.; Brun, Émilie; Mabondzo, Aloı̈se

doi:10.1038/s41598-017-12404-5

Cited by 54 publications

(42 citation statements)

References 56 publications

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“…5,6 A substantial amount of evidence has also demonstrated that NPs can cross the blood-brain barrier (BBB) and enter the brain to elicit further cytotoxicity. 7,8 Therefore, it is critical to assess the potential neurotoxic effects of NPs on brain function.…”

Section: Introductionmentioning

confidence: 99%

Silica nanoparticle exposure during the neonatal period impairs hippocampal precursor proliferation and social behavior later in life

Gao

Gong

et al. 2018

IJN

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IntroductionSilica nanoparticles (SiO2-NPs) are currently among the most widely used nanomaterials, but their potentially adverse effects on brain development remain unknown. The developing brain is extremely sensitive to NP neurotoxicity during the early postnatal period.Materials and methodsHerein, we investigated the effects of SiO2-NPs (doses of 10, 20, or 50 mg with a particle size of ~91 nm, equivalent to aerosol mass concentrations 55.56, 111.11, and 277.78 mg/m3, respectively) exposure from postnatal day (P) 1 to P7 on hippocampal precursor proliferation at P8 and long-term neurobehavior in adults.ResultsSiO2-NP exposure resulted in inflammatory cell infiltration in lung tissue, microglia over-activation in the hippocampal dentate gyrus (DG), and decreased hippocampal precursor proliferation in the DG-subgranular zone at P8. Moreover, after exposure to 20 mg of SiO2-NPs, mice exhibited social interaction deficits and slight anxiety-like behaviors in adulthood, but this exposure did not induce locomotor activity impairment, depression-like behavior, or short-term memory impairment.DiscussionThese findings suggest that early-age SiO2-NP exposure induced inflammation and inhibited precursor proliferation in the DG in a dose-dependent manner, which might be related to the social dysfunction observed in adulthood.

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Section: Introductionmentioning

confidence: 99%

Silica nanoparticle exposure during the neonatal period impairs hippocampal precursor proliferation and social behavior later in life

Gao

Gong

et al. 2018

IJN

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“…Our Ti doses were ca. one order of magnitude higher than that applied in a similar dosing regime in 15 which -10 mg/m 3 for 6 hours -corresponds to ca. 1.25 mg/kg on the basis of ventilation volume data published in 16 , and is itself higher than the 0.3 mg/m 3 occupational limit 9 .…”

Section: Doses and Treatmentmentioning

confidence: 77%

“…Likewise, breakdown of bloodbrain barrier and neuronal damage caused by metal NPs, given ip., was more severe with 20-30 nm than with 56-60 nm or >100 nm particles 29 . Blood-brain barrier damage was also observed in rats that inhaled nano-Ti 15 .…”

Section: Discussionmentioning

confidence: 90%

“…Rat-based models of nervous system effects of TiO 2 NPs are scarce in the literature 4 . Inhalation exposure of rats to 10 mg/m 3 nano-TiO 2 aerosol (daily 6 hours, 5 days a week for 4 weeks) resulted in increased level of inflammation markers and decreased expression of synaptophysin in the brain without relevant deposition of Ti 15 . In most other rat studies using airway application, pulmonary toxicity was investigated 16 and in some, the access of the NPs beyond the lungs was questioned 17 .…”

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confidence: 97%

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Functional neurotoxicity and tissue metal levels in rats exposed subacutely to titanium dioxide nanoparticles via the airways

Horváth¹,

Vezér²,

Kozma³

et al. 2018

Ideggyogy Sz

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“…87,88 Nano-TiO 2 toxicity on the brain, especially on the hippocampus, seems to be dosedependent. 87,88 In rats, the study by Horvath et al 90 showed a significant slow-down of sensory evoked potentials and tail nerve action potential, and the study by Disdier et al 91 evidenced a decreased expression of a neuronal activity marker (synaptophysin), exacerbated in older rats even if TiO 2 nanoparticles were not detected in the brain.…”

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confidence: 99%

Safety of titanium dioxide nanoparticles in cosmetics

Dréno¹,

Chuberre

et al. 2019

Acad Dermatol Venereol

189

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Titanium dioxide (TiO2) is widely used in a variety of products including cosmetics. TiO2 in its nanoparticle form (nano‐TiO2) is now the only form used as an ultraviolet (UV) filter in sunscreens, but also in some day creams, foundations and lip balms. While its efficacy as a UV filter is proven in the prevention of skin cancers and sunburns, some concerns have been raised about its safety. Indeed, considering its small size, nano‐TiO2 is suspected to penetrate dermal, respiratory or gastrointestinal barriers, disseminate in the body and therefore constitute a potential risk to the consumer. At the skin level, most studies performed in humans or animals showed that nano‐TiO2 did not penetrate beyond the outer layers of stratum corneum to viable cells and did not reach the general circulation, either in healthy or in compromised skin. The Scientific Committee on Consumer Safety (SCCS) considers nano‐TiO2 as a non‐sensitizer and as mild‐ or non‐irritant to skin and concludes in no evidence of carcinogenicity (supported by the European Chemicals Agency), mutagenicity or reproductive toxicity after dermal exposure to nano‐TiO2. According to the SCCS, nano‐TiO2 from sunscreens does not present any health risk when applied on the skin at a concentration up to 25%. However, the SCCS does not recommend the use of nano‐TiO2 in formulations that may lead to exposure of the consumer's lungs by inhalation (sprayable products and powders). Indeed, even if human data are sparse and inconsistent, lung inflammation was reported in animals. In 2016, the EU Cosmetic Regulation made nano‐TiO2 as an authorized UV filter, except in products that could lead to exposure of the lungs. After oral exposure, nano‐TiO2 absorption and toxicity are limited. The incidental oral exposure to nano‐TiO2 contained in lip balms is thus not expected to induce adverse health effects.

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Brain Inflammation, Blood Brain Barrier dysfunction and Neuronal Synaptophysin Decrease after Inhalation Exposure to Titanium Dioxide Nano-aerosol in Aging Rats

Cited by 54 publications

References 56 publications

Silica nanoparticle exposure during the neonatal period impairs hippocampal precursor proliferation and social behavior later in life

Silica nanoparticle exposure during the neonatal period impairs hippocampal precursor proliferation and social behavior later in life

Functional neurotoxicity and tissue metal levels in rats exposed subacutely to titanium dioxide nanoparticles via the airways

Safety of titanium dioxide nanoparticles in cosmetics

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