Dataset Information

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

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 SiO_2-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.

SUBMITTER: Fu J

PROVIDER: S-EPMC6018854 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

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

Fu Jingjing J Gao Junwei J Gong Linji L Ma Yuanyuan Y Xu Haiwei H Gu Zhanjun Z Zhu Jingci J Fan Xiaotang X

International journal of nanomedicine 20180622

<h4>Introduction</h4>Silica nanoparticles (SiO<sub>2</sub>-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.<h4>Materials and methods</h4>Herein, we investigated the effects of SiO<sub>2</sub>-NPs (doses of 10, 20, or 50 mg with a particle size of ~91 nm, equivalent to aerosol mass concentrations 55.56, 111.11, an ...[more]

PMID: 29950837

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Project description:BackgroundHippocampal oscillations play a critical role in the ontogeny of allocentric memory in rodents. During the critical period for memory development, hippocampal theta is the driving force behind the temporal coordination of neuronal ensembles underpinning spatial memory. While known that hippocampal oscillations are necessary for normal spatial cognition, whether disrupted hippocampal oscillatory activity during the critical period impairs long-term spatial memory is unknown. Here we investigated whether disruption of normal hippocampal rhythms during the critical period have enduring effects on allocentric memory in rodents.Objective/hypothesisWe hypothesized that disruption of hippocampal oscillations via artificial regulation of the medial septum during the critical period for memory development results in long-standing deficits in spatial cognition.MethodsAfter demonstrating that pan-neuronal medial septum (MS) optogenetic stimulation (465 nm activated) regulated hippocampal oscillations in weanling rats we used a random pattern of stimulation frequencies to disrupt hippocampal theta rhythms for either 1Hr or 5hr a day between postnatal (P) days 21-25. Non-stimulated and yellow light-stimulated (590 nm) rats served as controls. At P50-60 all rats were tested for spatial cognition in the active avoidance task. Rats were then sacrificed, and the MS and hippocampus assessed for cell loss. Power spectrum density of the MS and hippocampus, coherences and voltage correlations between MS and hippocampus were evaluated at baseline for a range of stimulation frequencies from 0.5 to 110 Hz and during disruptive hippocampal stimulation. Unpaired t-tests and ANOVA were used to compare oscillatory parameters, behavior and cell density in all animals.ResultsNon-selective optogenetic stimulation of the MS in P21 rats resulted in precise regulation of hippocampal oscillations with 1:1 entrainment between stimulation frequency (0.5-110 Hz) and hippocampal local field potentials. Across bandwidths MS stimulation increased power, coherence and voltage correlation at all frequencies whereas the disruptive stimulation increased power and reduced coherence and voltage correlations with most statistical measures highly significant (p < 0.001, following correction for false detection). Rats receiving disruptive hippocampal stimulation during the critical period for memory development for either 1Hr or 5hr had marked impairment in spatial learning as measured in active avoidance test compared to non-stimulated or yellow light-control rats (p < 0.001). No cell loss was measured between the blue-stimulated and non-stimulated or yellow light-stimulated controls in either the MS or hippocampus.ConclusionThe results demonstrated that robust regulation of hippocampal oscillations can be achieved with non-selective optogenetic stimulation of the MS in rat pups. A disruptive hippocampal stimulation protocol, which markedly increases power and reduces coherence and voltage correlations between the MS and hippocampus during the critical period of memory development, results in long-standing spatial cognitive deficits. This spatial cognitive impairment is not a result of optogenetic stimulation-induced cell loss.

Dataset Information

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

Introduction

Materials and methods

Results

Discussion

Publications

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

Similar Datasets

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