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

Int J Nanomedicine. 2018 Jun 22:13:3593-3608. doi: 10.2147/IJN.S160828. eCollection 2018.

Abstract

Introduction: Silica 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 methods: Herein, 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.

Results: SiO2-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.

Discussion: These 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.

Keywords: hippocampal neurogenesis; nanotoxicity; neuroinflammation; silica nanoparticles; social behavior.

MeSH terms

  • Animals
  • Anxiety / complications
  • Body Weight
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation
  • Dentate Gyrus / pathology
  • Depression / complications
  • Exploratory Behavior
  • Female
  • Hippocampus / pathology*
  • Inflammation / pathology
  • Locomotion
  • Lung / pathology
  • Male
  • Memory Disorders / complications
  • Memory Disorders / pathology
  • Mice, Inbred C57BL
  • Microglia / pathology
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Neural Stem Cells / metabolism
  • Neurogenesis / drug effects
  • Organ Size
  • Silicon Dioxide / chemistry*
  • Social Behavior*

Substances

  • Silicon Dioxide
  • Bromodeoxyuridine