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

Abstract

Jingjing Fu,1,2,* Junwei Gao,2,* Linji Gong,3,4 Yuanyuan Ma,1 Haiwei Xu,5 Zhanjun Gu,3,4 Jingci Zhu,1 Xiaotang Fan2 1School of Nursing, Third Military Medical University, Chongqing 400038, China; 2Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing 400038, China; 3Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China; 4University of Chinese Academy of Sciences, Beijing 100049, China; 5Southwest Eye Hospital/Southwest Hospital, Third Military Medical University, Chongqing 400038, China *These authors contributed equally to this work 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: silica nanoparticles, nanotoxicity, hippocampal neurogenesis, neuroinflammation, social behavior

Keywords

• Silica nanoparticles
• Nanotoxicity
• Hippocampal neurogenesis
• Neuroinflammation
• Social behavior