Progress in Chemistry 2021, Vol. 33 Issue (5): 713-725 DOI: 10.7536/PC210102   Next Articles

• Original article •

Neurotoxicity Induced by Atmospheric Fine Particulate Matters and the Underlying Molecular Mechanism

Yuzhu Zhang1,2, Jing Zhan1, Qian S. Liu1,*(), Qunfang Zhou1,2,3, Guibin Jiang1   

  1. 1 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
    2 College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
    3 School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310000, China
  • Received: Revised: Online: Published:
  • Contact: Qian Liu
  • Supported by:
    National Natural Science Foundation of China(91943301); National Natural Science Foundation of China(21806178); National Natural Science Foundation of China(21527901)
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The health effect of atmospheric fine particulate matters(PMs) is now being increasingly concerned, and a growing number of epidemiological studies have reported the adverse impacts of PMs on the respiratory system, cardiovascular system, etc. However, whether PMs can enter the brain and cause neurotoxicities or not remains unknown, which has been an important research direction for the health risk evaluation of atmospheric smog in recent years. Based on the relevant epidemiological studies and experimental evidences in vitro and in vivo, this paper summarizes the potential pathways regulating the neurotoxicity of atmospheric PMs, their detrimental effects on the adult, elderly, and developmental nervous systems, as well as the underlying molecular mechanisms. Atmospheric PMs were reported to affect the nervous system through the blood-brain barrier pathway, the olfactory nerve pathway, the microbiota-gut-brain axis, etc. Herein, oxidative stress, mitochondrial damage, inflammation, DNA damage, epigenetic regulation, hematological homeostasis, and several key signaling pathways were found to be involved in the observed neurotoxicities caused by atmospheric PM exposure. This review aims to reveal the neurotoxicities of atmospheric PMs, especially their neurodevelopmental effects on special populations such as children. On this basis, this article points out the future research directions in this field, providing a theoretical basis for the evaluation of neurotoxicities and public health hazards of atmospheric PMs.


1 Introduction

2 Epidemiological studies on neurological diseases induced by PM exposure

2.1 Developmental nervous system

2.2 Adult nervous system

2.3 Elderly nervous system

3 Pathways by which PMs affect the nervous system

3.1 The blood-brain barrier pathway

3.2 The olfactory nerve pathway

3.3 Other pathways

4 Experimental findings on neurotoxic effects of PMs

4.1 In vitro experiments

4.2 In vivo experiments

5 Molecular mechanisms underlying the neurotoxicities of PMs

5.1 Oxidative stress and mitochondrial damage

5.2 Inflammation

5.3 Key signaling pathways regulating the neurotoxicities of PMs

5.4 DNA damage and epigenetic regulation

5.5 Effects on hematological homeostasis

6 Prospects and research points

Table 1 The epidemiological findings on neurological effects of atmospheric particulate matters
Population Scale Research design Exposure method Exposure estimate Main findings ref
Pregnant women
living in four
residential areas of
74 671 Multiple linear
regression, logistic
Total suspended particles(TSP), SO2 Low birth weight Wang
et al.[46]
Preterm birth records in Pennsylvania(1997~2001) Time-series analysis PM10, SO2 Increase in preterm birth risk Sagiv
et al.[48]
Birth records in Atlanta(1994-2004) 476 489 Time-series analysis, Poisson
generalized linear
PM10, PM2.5,
NO, NO2,
SO2, O3
Data collected from air quality monitors Increase in preterm birth risk Darrow
et al.[47]
Urban children 267 Distributed lag
models, intelligence assessment
PM2.5 Spatio-temporally resolved prediction
Exposure in specific prenatal windows was associated with poor intellectual functions Chiu
et al.[51]
Representative children in Japan since 2001 33 911 Multilevel logistic
regression analysis
PMs, NO2,
Stunting Yorifuji
et al.[52]
Newborns of Rome
GASPII project
719 Wechsler Intelligence Scale for Children-Ⅲ, linear
regression model
PM2.5, NO2 Land use regression
Cognitive impairment Porta
et al.[53]
Mother-child pairs in
1109 Linear regression
PM2.5, black
Space-time LUR model Partial cognitive
et al.[54]
NHS II autism spectrum disorder children(USA) 245 Linear regression
PM2.5, PM2.5-10 Spatio-temporal prediction model PM2.5 is associated with an increased risk of autism Raanan
et al.[60]
Autism children born in Carolina 979 Multiple regression
PM10 Statistical interpolation method Third-trimester exposure is associated with an increased risk of autism Kalkbrenner
et al.[58]
Children from 39 schools in Barcelona exposed to traffic-related air
pollution(7~10 y)
2715 Stratified analyses Traffic source
Linear mixed effects models Higher traffic-related air pollution made children a smaller improvement in cognitive development Sunyer
et al.[63]
Patients with acute
ischemic stroke in
Ontario, Canada
9202 Time-stratified case-crossover design, random-effects meta-analysis techniques Increased risk of
particulate-related ischemic strokes
et al.[30]
City populations with high-level exposure to air pollution Cognitive and
neurological integrity testing, genome
Accumulation of COX2 and Aβ42 in nerve cells Lilian
et al.[64]
Healthy adults 27 Serum and plasma were collected and analyzed for inflammatory cytokines Filtered air
(FA) and diesel exhaust(DE)
Cortical stress response Cliff
et al.[74]
Populations in northern Sweden 1806 Cohort analysis PM2.5-10, PM2.5 Spatiotemporal smoothing model Cognitive decline was speed up Oudin
et al.[66]
MS-related hospitalization in
Lombardy region, Italy,(2001~2009)
8287 Poisson regression analysis PM10 Daily concentrations
from 53 monitoring sites
Determining MS
occurrence and relapses
et al.[65]
Populations(> 65 y) 95 690 Cohort study, Cox proportional hazards model O3, PM2.5 Air data from Taiwan Environmental Protection Agency Long-term exposure
increased the risk of AD
et al.[73]
US women(70~81y) 19 409 Cognitive test Exposure to
PM2.5-10 and
PM2.5 in the last month or for a long term of 7~14 years
Geographic information system-based spatiotemporal smoothing models Cognitive decline of old women Weuve
et al.[13]
Table 2 Experimental findings on neurotoxic effects of PMs
Experimental model Exposure method Exposure time Main findings ref
In vivo In vitro
/ Primary mouse
hippocampal neurons
PM2.5 24 h PM2.5 elevated COX-2 expression,increased the amplitude of excitatory postsynaptic potentials by ROS-NF-κB pathway Li et al.[38]
/ Rat microglia SiO2NPs, TiO2NPs, HAPNPs, Fe3O4NPs 24 h Microglial activation and the release of proinflammatory factors Xue et al.[89]
/ Human neuroblastoma SH-SY5Y cells Diesel exhaust particle 3, 24 h Gluconeogenesis Ji et al.[90]
/ Human neuroblastoma SH-SY5Y cells PM2.5 and its extracts 72 h Oxidative stress-mediated abnormal DNA hydroxymethylation Wei et al.[91]
/ Mixed glia derived from neonatal rat cerebral cortex. traffic ultrafine
particulate matter
24 h Microglia-derived TNF-α increased Cheng
et al.[33]
/ Primary culture of mouse olfactory bulb and olfactory
epithelial cells
Urban traffic ultrafine particulate matter
(< 200 nm)
5, 20, 45 h inflammation during different time courses Cheng
et al.[79]
/ BV-2 microglia am-PM2.5, pm-PM2.5 24 h Am-PM2.5 had a higher pro-
inflammatory activity than pm-PM2.5
et al.[92]
C57BL/6J mice / PM2.5, SO2 and NO2 co-exposure 28 days Impaired spatial learning and memory, mitochondrial dysfunction Ku et al.[40]
Male SD rat / PM2.5 12 weeks Morphological abnormalities of the hippocampus, abnormal expression of neurotransmitters and receptors. Li et al.[93]
Nrf2-/- mice Astrocyte PM2.5 24 weeks NF-κB induced metabolic disorders and neuroinflammation Xu et al.[96]
C57BL/6 mice
/ PMs 6 h/day
(30 days)
Disruption of blood-brain barrier and increased inflammatory marker expression Oppenheim et al.[100]
ApoE-/- mice / Low concentrations of PM2.5 6 h/day
(30 days)
PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis Sun et al.[99]
ApoE-/- mice / Mixture of gasoline and diesel engine exhaust 6 h/day
(30 days)
Increased levels of oxidative stress in microvascular Lucero et al.[101]
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