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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.

Contents

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

Key words: atmospheric fine particulate matters, neurotoxicity, epidemiological study, molecular mechanism
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
Beijing(1988~1991) 		74 671 Multiple linear
regression, logistic
regression 		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
models 		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
model 		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,
SO2 		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
models 		Cognitive impairment Porta
et al.[53]
Mother-child pairs in
Massachusetts(USA) 		1109 Linear regression
models 		PM2.5, black
carbon(BC) 		Space-time LUR model Partial cognitive
decline 		Harris
et al.[54]
NHS II autism spectrum disorder children(USA) 245 Linear regression
models 		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
analysis 		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
UFP 		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 		O’Donnell
et al.[30]
City populations with high-level exposure to air pollution Cognitive and
neurological integrity testing, genome
analysis 		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 		Laura
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 		Zhong
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 		Lovett
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]
ApoE-/-mice,
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]
[1]
Van Donkelaar A, Martin R V, Brauer M, Boys B L. Environ. Health Perspect., 2015, 123(2):135.

doi: 10.1289/ehp.1408646
[2]
Xu X H, Ha S U, Basnet R. Front Public Health, 2016, 4:157.
[3]
江桂斌(Jiang G B ), 王春霞(Wang C X ), 张爱茜(Zhang A Q). 大气细颗粒物的毒理与健康效应(Toxicology and Health Effects of Atmospheric Fine Particles). 北京:科学出版社 (Beijing: Science Press), 2020.1.
[4]
World Health Organization. Public Health Environ., 2014.
[5]
Tao Y, Liu Y, Mi S, Guo Y. Acta Sci. Circum. 2014, 34(3):592.
[6]
Huang X, Han X, Li S, Yang H, Huang C, Huang T. Res. Environ. Sci., 2017, 30(7):1001.
[7]
Peters A, Veronesi B, Calderón-Garcidueñas L, Gehr P, Chen L C, Geiser M, Reed W, Rothen-Rutishauser B, Schürch S, Schulz H. Part. Fibre Toxicol., 2006, 3(1):1.

doi: 10.1186/1743-8977-3-1
[8]
Tian Y Z, Chen G, Wang H T, Huang-Fu Y Q, Shi G L, Han B, Feng Y C. Chemosphere, 2016, 147:256.

doi: 10.1016/j.chemosphere.2015.12.132
[9]
Tonne C, Elbaz A, Beevers S, Singh-Manoux A. Epidemiology, 2014, 25(5):674.

doi: 10.1097/EDE.0000000000000144
[10]
Ranft U, Schikowski T, Sugiri D, Krutmann J, Krämer U. Environ. Res., 2009, 109(8):1004.

doi: 10.1016/j.envres.2009.08.003
[11]
Gatto N M, Henderson V W, Hodis H N, St John J A, Lurmann F, Chen J C, Mack W J. NeuroToxicology, 2014, 40:1.

doi: 10.1016/j.neuro.2013.09.004
[12]
Chen J C, Schwartz J. NeuroToxicology, 2009, 30(2):231.

doi: 10.1016/j.neuro.2008.12.011
[13]
Weuve J, Puett R C, Schwartz J, Yanosky J D, Laden F, Grodstein F. Arch Intern Med, 2012, 172(3):219.

doi: 10.1001/archinternmed.2011.683
[14]
Ailshire J A, Crimmins E M. Am. J. Epidemiol., 2014, 180(4):359.

doi: 10.1093/aje/kwu155
[15]
Ku T T, Chen M J, Li B, Yun Y, Li G K, Sang N. Toxicol. Res., 2017, 6(1):7.

doi: 10.1039/C6TX00314A
[16]
Pardo M, Qiu X H, Zimmermann R, Rudich Y. Chem. Res. Toxicol. 2020, 33(5):1110.

doi: 10.1021/acs.chemrestox.0c00007
[17]
Calderón-Garcidueñas L, Calderón-Garcidueñas A, Torres-Jardón R, Avila-Ramírez J, Kulesza R J, Angiulli A D. Prim. Heal. Care Res. Dev., 2015, 16(4):329.
[18]
Bernstein J A, Alexis N, Barnes C, Bernstein I L, Nel A, Peden D, Diaz-Sanchez D, Tarlo S M, Williams P B, Bernstein J A. J. Allergy Clin. Immunol., 2004, 114(5):1116.

doi: 10.1016/j.jaci.2004.08.030
[19]
Dockery D W, Pope C A, Xu X P, Spengler J D, Ware J H, Fay M E, Ferris B G, Speizer F E. N Engl J. Med., 1993, 329(24):1753.

doi: 10.1056/NEJM199312093292401
[20]
Dockery D W. Environ. Health Perspect., 2001, 109:483.
[21]
Dockery D W, Pope C A. Annu. Rev. Public Heal., 1994, 15(1):107.
[22]
Møller P, Jacobsen N R, Folkmann J K, Danielsen P H, Mikkelsen L, Hemmingsen J G, Vesterdal L K, Forchhammer L, Wallin H, Loft S. Free. Radic. Res., 2010, 44(1):1.

doi: 10.3109/10715760903300691
[23]
Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C. Inhal. Toxicol., 2004, 16(6/7):437.

doi: 10.1080/08958370490439597
[24]
Wu Y C, Lin Y C, Yu H L, Chen J H, Chen T F, Sun Y, Wen L L, Yip P K, Chu Y M, Chen Y C. Alzheimer’s Dement.: Diagn. Assess. Dis. Monit., 2015, 1(2):220.
[25]
Mutlu E A, Comba I Y, Cho T, Engen P A, Yazıcı C, Soberanes S, Hamanaka R B, Niğdelioğlu R, Meliton A Y, Ghio A J, Budinger G R S, Mutlu G M. Environ. Pollut., 2018, 240:817.

doi: 10.1016/j.envpol.2018.04.130
[26]
Lombardi V C, de Meirleir K L, Subramanian K, Nourani S M, Dagda R K, Delaney S L, Palotás A. J. Nutr. Biochem., 2018, 61:1.

doi: 10.1016/j.jnutbio.2018.04.004
[27]
Shou Y K, Huang Y L, Zhu X Z, Liu C Q, Hu Y, Wang H H. Ecotoxicol. Environ. Saf., 2019, 174:344.

doi: 10.1016/j.ecoenv.2019.02.086
[28]
Malek A M, Barchowsky A, Bowser R, Heiman-Patterson T, Lacomis D, Rana S, Youk A, Talbott E O. Environ. Pollut., 2015, 197:181.

doi: 10.1016/j.envpol.2014.12.010
[29]
Calderón-Garcidueñas L, Avila-Ramírez J, Calderón-Garcidueñas A, González-Heredia T, Acuña-Ayala H, Chao C K, Thompson C, Ruiz-Ramos R, Cortés-González V, Martínez-Martínez L, García-Pérez M A, Reis J, Mukherjee P S, Torres-Jardón R, Lachmann I. J. Alzheimer’s Dis., 2016, 54(2):597.
[30]
O’donnell M J, Fang J, Mittleman M A, Kapral M K, Wellenius G A, Epidemiology, 2011, 22(3):422.

doi: 10.1097/EDE.0b013e3182126580
[31]
Lim Y H, Kim H, Kim J H, Bae S, Park H Y, Hong Y C. Environ. Heal. Perspect., 2012, 120(7):1023.

doi: 10.1289/ehp.1104100
[32]
Lampron A, ElAli A, Rivest S. Neuron, 2013, 78(2):214.

doi: 10.1016/j.neuron.2013.04.005
[33]
Cheng H, Davis D A, Hasheminassab S, Sioutas C, Morgan T E, Finch C E. J. Neuroinflammation, 2016, 13(1):1.

doi: 10.1186/s12974-015-0467-5
[34]
Hogan M K, Kovalycsik T, Sun Q H, Rajagopalan S, Nelson R J. Behav. Brain Res., 2015, 294:81.

doi: 10.1016/j.bbr.2015.07.033
[35]
Verma V, Fang T, Xu L, Peltier R E, Russell A G, Ng N L, Weber R J. Environ. Sci. Technol., 2015, 49(7):4646.

doi: 10.1021/es505577w
[36]
Berson A, Nativio R, Berger S L, Bonini N M. Trends Neurosci., 2018, 41(9):587.

doi: 10.1016/j.tins.2018.05.005
[37]
Gondalia R, Baldassari A, Holliday K M, Justice A E, Méndez-Giráldez R, Stewart J D, Liao D P, Yanosky J D, Brennan K J M, Engel S M, Jordahl K M, Kennedy E, Ward-Caviness C K, Wolf K, Waldenberger M, Cyrys J, Peters A, Bhatti P, Whitsel E A. Environ. Int., 2019, 132:104723.

doi: S0160-4120(18)32932-5 pmid: 31208937
[38]
Li B, Guo L, Ku T T, Chen M J, Li G K, Sang N. Chemosphere, 2018, 190:124.

doi: 10.1016/j.chemosphere.2017.09.098
[39]
Acaz-Fonseca E, Ortiz-Rodriguez A, Azcoitia I, Garcia-Segura L M, Arevalo M A. Cell Death Discov., 2019, 5(1):1.
[40]
Ku T T, Ji X T, Zhang Y Y, Li G K, Sang N. Chemosphere, 2016, 163:27.

doi: 10.1016/j.chemosphere.2016.08.009
[41]
Calderón-Garcidueñas L, Engle R, Mora-Tiscareño A, Styner M, Gómez-Garza G, Zhu H T, Jewells V, Torres-Jardón R, Romero L, Monroy-Acosta M E, Bryant C, González-González L O, Medina-Cortina H, D’Angiulli A. Brain Cogn., 2011, 77(3):345.

doi: 10.1016/j.bandc.2011.09.006 pmid: 22032805
[42]
Brown R C, Lockwood A H, Sonawane B R. Environ. Heal. Perspect., 2005, 113(9):1250.

doi: 10.1289/ehp.7567
[43]
Guxens M, Sunyer J. Swiss Med Wkly, 2012, 141:w13322.
[44]
Fox M A, Tran N L, Groopman J D, Burke T A. Regul. Toxicol. Pharmacol., 2004, 40(3):305.

doi: 10.1016/j.yrtph.2004.07.008
[45]
Landrigan P J, Sonawane B, Butler R N, Trasande L, Callan R, Droller D. Environ. Heal. Perspect., 2005, 113(9):1230.

doi: 10.1289/ehp.7571
[46]
Wang X, Ding H, Ryan L, Xu X. Environ. Heal. Perspect., 1997, 105(5):514.

doi: 10.1289/ehp.97105514
[47]
Darrow L A, Klein M, Flanders W D, Waller L A, Correa A, Marcus M, Mulholland J A, Russell A G, Tolbert P E. Epidemiology, 2009, 20(5):689.

doi: 10.1097/EDE.0b013e3181a7128f
[48]
Sagiv S K, Mendola P, Loomis D, Herring A H, Neas L M, Savitz D A, Poole C. Environ. Heal. Perspect., 2005, 113(5):602.

doi: 10.1289/ehp.7646
[49]
Choi H, Rauh V, Garfinkel R, Tu Y, Perera F P. Environ. Heal. Perspect., 2008, 116(5):658.

doi: 10.1289/ehp.10958
[50]
Marshall E G, Harris G, Wartenberg D. Birth Defects Res. Part A: Clin. Mol. Teratol., 2010, 88(4):205.

doi: 10.1002/bdra.v88:4
[51]
Chiu Y H M, Hsu H H L, Coull B A, Bellinger D C, Kloog I, Schwartz J, Wright R O, Wright R J. Environ. Int., 2016, 87:56.

doi: 10.1016/j.envint.2015.11.010
[52]
Yorifuji T, Kashima S, Diez M H, Kado Y, Sanada S, Doi H. Epidemiology, 2016, 27(1):57.

doi: 10.1097/EDE.0000000000000361 pmid: 26247490
[53]
Porta D, Narduzzi S, Badaloni C, Bucci S, Cesaroni G, Colelli V, Davoli M, Sunyer J, Zirro E, Schwartz J, Forastiere F. Epidemiology, 2015:1.
[54]
Harris M H, Gold D R, Rifas-Shiman S L, Melly S J, Zanobetti A, Coull B A, Schwartz J D, Gryparis A, Kloog I, Koutrakis P, Bellinger D C, White R F, Sagiv S K, Oken E. Environ. Heal. Perspect., 2015, 123(10):1072.

doi: 10.1289/ehp.1408803
[55]
Liu J H, Lewis G. J Environ Health, 2014, 76(6):130.
[56]
Zanchi A C T, Fagundes L S, Barbosa F, Bernardi R, Rhoden C R, Saldiva P H N, do Valle A C,. Inhal. Toxicol., 2010, 22(11):910.

doi: 10.3109/08958378.2010.494313 pmid: 20569119
[57]
Genc S, Zadeoglulari Z, Fuss S H, Genc K. J. Toxicol., 2012, 2012:1.
[58]
Kalkbrenner A E, Windham G C, Serre M L, Akita Y, Wang X X, Hoffman K, Thayer B P, Daniels J L. Epidemiology, 2015, 26(1):30.

doi: 10.1097/EDE.0000000000000173 pmid: 25286049
[59]
Talbott E O, Arena V C, Rager J R, Clougherty J E, Michanowicz D R, Sharma R K, Stacy S L. Environ. Res., 2015, 140:414.

doi: 10.1016/j.envres.2015.04.021
[60]
Raz R, Roberts A L, Lyall K, Hart J E, Just A C, Laden F, Weisskopf M G. Environ. Health Perspect., 2015, 123(3):264.

doi: 10.1289/ehp.1408133
[61]
Polanczyk G, de Lima M S, Horta B L, Biederman J, Rohde L A. Am. J. Psychiatry, 2007, 164(6):942.

doi: 10.1176/ajp.2007.164.6.942
[62]
Donzelli G, Llopis-Gonzalez A, Llopis-Morales A, Cioni L, Morales-Suárez-varela M. Int. J. Environ. Res. Public Heal., 2019, 17(1):67.
[63]
Sunyer J, Esnaola M, Alvarez-Pedrerol M, Forns J, Rivas I, López-Vicente M, Suades-González E, Foraster M, Garcia-Esteban R, Basagaña X, Viana M, Cirach M, Moreno T, Alastuey A, Sebastian-Galles N, Nieuwenhuijsen M, Querol X. PLoS Med., 2015, 12(3):e1001792.

doi: 10.1371/journal.pmed.1001792
[64]
Calderón-Garcidueñas L, Reed W, Maronpot R R, Henriquez-Roldán C, Delgado-Chavez R, Calderón-Garcidueñas A, Dragustinovis I, Franco-Lira M, Aragón-Flores M, Solt A C, Altenburg M, Torres-Jardón R, Swenberg J A. Toxicol. Pathol., 2004, 32(6):650.

pmid: 15513908
[65]
Angelici L, Piola M, Cavalleri T, Randi G, Cortini F, Bergamaschi R, Baccarelli A A, Bertazzi P A, Pesatori A C, Bollati V. Environ. Res., 2016, 145:68.

doi: 10.1016/j.envres.2015.11.017
[66]
Oudin A, Forsberg B, Adolfsson A N, Lind N, Modig L, Nordin M, Nordin S, Adolfsson R, Nilsson L G. Environ. Heal. Perspect., 2016, 124(3):306.

doi: 10.1289/ehp.1408322
[67]
Anderson H R, Atkinson R W, Bremner S A, Marston L. Eur. Respir. J., 2003, 21:39.
[68]
Goldberg M S, Burnett R T, Bailar J C, Tamblyn R, Ernst P, Flegel K, Brook J, Bonvalot Y, Singh R, Valois M F, Vincent R. Environ. Heal. Perspect., 2001, 109:487.
[69]
Calderón-Garcidueñas L, Kavanaugh M, Block M, D’Angiulli A, Delgado-Chávez R, Torres-Jardón R, González-Maciel A, Reynoso-Robles R, Osnaya N, Villarreal-Calderon R, Guo R X, Hua Z W, Zhu H T, Perry G, Diaz P. J. Alzheimer’s Dis., 2012, 28(1):93.
[70]
Levesque S, Surace M J, McDonald J, Block M L. J. Neuroinflammation, 2011, 8(1):1.

doi: 10.1186/1742-2094-8-1
[71]
Calderón-Garcidueñas L, Mora-Tiscareño A, Ontiveros E, Gómez-Garza G, Barragán-Mejía G, Broadway J, Chapman S, Valencia-Salazar G, Jewells V, Maronpot R R, Henríquez-Roldán C, Pérez-Guillé B, Torres-Jardón R, Herrit L, Brooks D, Osnaya-Brizuela N, Monroy M E, González-Maciel A, Engle R W. Brain Cogn., 2008, 68(2):117.

doi: 10.1016/j.bandc.2008.04.008 pmid: 18550243
[72]
Inserra S G, Phifer B L, Anger W K, Lewin M, Hilsdon R, White M C. Environ. Res., 2004, 95(1):53.

pmid: 15068930
[73]
Jung C R, Lin Y T, Hwang B F. J. Alzheimers Dis., 2015, 44(2):573.

doi: 10.3233/JAD-140855
[74]
Cliff R, Curran J, Hirota J A, Brauer M, Feldman H, Carlsten C. Inhal. Toxicol., 2016, 28(3):145.

doi: 10.3109/08958378.2016.1145770
[75]
Chen R, Hu B, Liu Y, Xu J X, Yang G S, Xu D D, Chen C Y. Biochim. et Biophys. Acta BBA-Gen. Subj., 2016, 1860(12):2844.
[76]
Miller D S, Bauer B, Hartz A M. Pharmacol. Rev., 2008, 60(2):196.

doi: 10.1124/pr.107.07109
[77]
Block M L, Elder A, Auten R L, Bilbo S D, Chen H L, Chen J C, Cory-Slechta D A, Costa D, Diaz-Sanchez D, Dorman D C, Gold D R, Gray K, Jeng H A, Kaufman J D, Kleinman M T, Kirshner A, Lawler C, Miller D S, Wright R J. Neuro Toxicology, 2012, 33(5):972.
[78]
Elder A, Gelein R, Silva V, Feikert T, Opanashuk L, Carter J, Potter R, Maynard A, Ito Y, Finkelstein J, Oberdörster G. Environ. Heal. Perspect., 2006, 114(8):1172.

doi: 10.1289/ehp.9030
[79]
Cheng H, Saffari A, Sioutas C, Forman H J, Morgan T E, Finch C E. Environ. Health Perspect., 2016, 124(10):1537.

doi: 10.1289/EHP134
[80]
Beattie E C, Stellwagen D, Morishita W, Bresnahan J C, Ha B K, Von Zastrow M, Beattie M S, Malenka R C. Science, 2002, 295(5563):2282.

doi: 10.1126/science.1067859
[81]
Sender R, Fuchs S, Milo R. PLoS Biol, 2016, 14(8):e1002533.

doi: 10.1371/journal.pbio.1002533
[82]
Sanmarco L M, Wheeler M A, Gutiérrez-Vázquez C, Polonio C M, Linnerbauer M, Pinho-Ribeiro F A, Li Z R, Giovannoni F, Batterman K V, Scalisi G, Zandee S E J, Heck E S, Alsuwailm M, Rosene D L, Becher B, Chiu I M, Prat A, Quintana F J. Nature, 2021, 590(7846):473.

doi: 10.1038/s41586-020-03116-4
[83]
Ning Y Y, Imrich A, Goldsmith C A, Qin C Z, Kobzik L. J. Toxic. Environ. Health A., 2000, 59(3):165.

doi: 10.1080/009841000156952
[84]
Biesmans S, Meert T F, Bouwknecht J A, Acton P D, Davoodi N, de Haes P, Kuijlaars J, Langlois X, Matthews L J R, Ver Donck L, Hellings N, Nuydens R. Mediat. Inflamm., 2013, 2013:1.
[85]
Mutlu E A, Engen P A, Soberanes S, Urich D, Forsyth C B, Nigdelioglu R, Chiarella S E, Radigan K A, Gonzalez A, Jakate S, Keshavarzian A, Budinger G S, Mutlu G M. Part. Fibre Toxicol., 2011, 8(1):1.

doi: 10.1186/1743-8977-8-1
[86]
Nemmar A, Holme J A, Rosas I, Schwarze P E, Alfaro-Moreno E. Biomed Res. Int., 2013, 2013:1.
[87]
Silva R F M, Falcão A S, Fernandes A, Gordo A C, Brito M A, Brites D. Toxicol. Lett., 2006, 163(1):1.

pmid: 16257146
[88]
Lu M, Yan X F, Si Y, Chen X Z. Inflammation, 2019, 42(5):1693.

doi: 10.1007/s10753-019-01029-7
[89]
Xue Y, Wu J, Sun J. Toxicol. Lett., 2012, 214(2):91.

doi: 10.1016/j.toxlet.2012.08.009
[90]
Ji Y, Stone C, Guan L F, Peng C Y, Han W. Neurol. Res., 2019, 41(8):742.

doi: 10.1080/01616412.2019.1609170
[91]
Wei H Y, Feng Y, Liang F, Cheng W, Wu X M, Zhou R, Wang Y. Toxicology, 2017, 380:94.

doi: 10.1016/j.tox.2017.01.017
[92]
Lovett C, Cacciottolo M, Shirmohammadi F, Haghani A, Morgan T E, Sioutas C, Finch C E. F1000 Research, 2018, 7:596.
[93]
Li Q Z, Zheng J L, Xu S, Zhang J S, Cao Y H, Qin Z L, Liu X Q, Jiang C Y. Toxicol Res., 2018, 7(6):1144.

doi: 10.1039/C8TX00093J
[94]
Tian X Y, Yun S F, Guo L Q, Dong M, Xu L X, Zhao Z G. Chin. J. Comp. Med., 2009, 19(2):50.
( 田小芸, 恽时锋, 郭联庆, 董敏, 许龙祥, 赵志刚. 中国比较医学杂志, 2009, 19(2):50.).
[95]
Li J, Stein T D, Johnson J A. Physiol. Genom., 2004, 18(3):261.

doi: 10.1152/physiolgenomics.00209.2003
[96]
Xu M X, Zhu Y F, Chang H F, Liang Y. Free. Radic. Biol. Med., 2016, 99:259.

doi: 10.1016/j.freeradbiomed.2016.08.021
[97]
Mahley R W, Nathan B P, Pitas R E. New York Acad. Sciences, 1996.139.
[98]
Yang X L, Zhang W G. Chin. J. Geront., 2006, 26(7):999.
[99]
Sun Q H, Wang A X, Jin X M, Natanzon A, Duquaine D, Brook R D, Aguinaldo J G, Fayad Z A, Fuster V, Lippmann M, Chen L C, Rajagopalan S. JAMA, 2005, 294(23):3003.

doi: 10.1001/jama.294.23.3003
[100]
Calderón-Garcidueñas L, Solt A C, Henríquez-Roldán C, Torres-Jardón R, Nuse B, Herritt L, Villarreal-Calderón R, Osnaya N, Stone I, García R, Brooks D M, González-Maciel A, Reynoso-Robles R, Delgado-Chávez R, Reed W. Toxicol. Pathol., 2008, 36(2):289.

doi: 10.1177/0192623307313011 pmid: 18349428
[101]
Lucero J, Suwannasual U, Herbert L M, McDonald J D, Lund A K. Inhal. Toxicol., 2017, 29(6):266.

doi: 10.1080/08958378.2017.1357774 pmid: 28816559
[102]
Lodovici M, Bigagli E. J. Toxicol., 2011, 2011:1.
[103]
Sarma S N, Blais J M, Chan H M. J. Toxicol. Environ. Heal. Part A, 2017, 80(5):285.
[104]
Wang Y, Zhang M, Li Z P, Yue J W, Xu M, Zhang Y H, Yung K K L, Li R J. Chemosphere, 2019, 218:577.

doi: 10.1016/j.chemosphere.2018.11.149
[105]
Knaapen A M, Schins R P F, Polat D, Becker A, Borm P J A. Mol. Cell. Biochem., 2002, 234(1):143.
[106]
Islam M T. Neurol. Res., 2017, 39(1):73.

doi: 10.1080/01616412.2016.1251711
[107]
Zhang Q, Li Q Z, Ma J C, Zhao Y P. Environ. Pollut., 2018, 242:994.

doi: 10.1016/j.envpol.2018.07.031
[108]
Saijo K, Winner B, Carson C T, Collier J G, Boyer L, Rosenfeld M G, Gage F H, Glass C K. Cell, 2009, 137(1):47.

doi: 10.1016/j.cell.2009.01.038
[109]
Glass C K, Saijo K, Winner B, Marchetto M C, Gage F H. Cell, 2010, 140(6):918.

doi: 10.1016/j.cell.2010.02.016
[110]
Crumrine R C, Thomas A L, Morgan P F. J. Cereb. Blood Flow Metab., 1994, 14(6):887.

doi: 10.1038/jcbfm.1994.119
[111]
Campbell A, Araujo J A, Li H H, Sioutas C, Kleinman M. J. Nanosci. Nanotechnol., 2009, 9(8):5099.

doi: 10.1166/jnn.2009.GR07
[112]
Chen X Y, Liu S, Zhang W, Wu C Y, Liu H C, Zhang F, Lu Z B, Ding W J. Biochem. Biophys. Res. Commun., 2018, 505(4):1154.

doi: 10.1016/j.bbrc.2018.10.057
[113]
Gualtieri M, Øvrevik J, Mollerup S, Asare N, Longhin E, Dahlman H J, Camatini M, Holme J A. Mutat. Res. Mol. Mech. Mutagen., 2011, 713(1/2):18.
[114]
Gualtieri M, Øvrevik J, Holme J A, Perrone M G, Bolzacchini E, Schwarze P E, Camatini M. Toxicol. Vitro, 2010, 24(1):29.

doi: 10.1016/j.tiv.2009.09.013
[115]
Oh S M, Kim H R, Park Y J, Lee S Y, Chung K H. Mutat. Res. Toxicol. Environ. Mutagen., 2011, 723(2):142.

doi: 10.1016/j.mrgentox.2011.04.003
[116]
Wang T, Pan Q, Lin L, Szulwach K E, Song C X, He C, Wu H, Warren S T, Jin P, Duan R H, Li X K. Hum. Mol. Genet., 2012, 21(26):5500.

doi: 10.1093/hmg/dds394
[117]
Liang J, Yang F, Zhao L, Bi C W, Cai B Z. Oncotarget, 2016, 7(30):48813.

doi: 10.18632/oncotarget.9281 pmid: 27183914
[118]
Wei H Y, Liang F, Meng G, Nie Z Q, Zhou R, Cheng W, Wu X M, Feng Y, Wang Y. Sci. Rep., 2016, 6(1):1.

doi: 10.1038/s41598-016-0001-8
[119]
Lu D W, Luo Q, Chen R, Zhuansun Y X, Jiang J, Wang W C, Yang X Z, Zhang L Y, Liu X L, Li F, Liu Q, Jiang G B. Nat. Commun., 2020, 11(1):1.

doi: 10.1038/s41467-019-13993-7
[120]
Jin X T, Ma Q C, Sun Z D, Yang X Z, Zhou Q F, Qu G B, Liu Q, Liao C Y, Li Z Y, Jiang G B. Environ. Sci. Technol., 2019, 53(5):2840.

doi: 10.1021/acs.est.8b05817
[121]
Gofrit S G, Shavit-Stein E. Neural Regen Res, 2019, 14(12):2043.

doi: 10.4103/1673-5374.262568 pmid: 31397331
[122]
Kaplan L, Chow B W, Gu C H. Nat. Rev. Neurosci., 2020, 21(8):416.

doi: 10.1038/s41583-020-0322-2
[123]
Maher B A, Ahmed I A M, Karloukovski V, MacLaren D A, Foulds P G, Allsop D, Mann D M A, Torres-Jardón R, Calderon-Garciduenas L. PNAS, 2016, 113(39):10797.

doi: 10.1073/pnas.1605941113
[1] Xiaojuan Wang, Zhenzhen Liu, Qi Chen, Xiaoqiang Wang, Fang Huang. Interactions between Graphene Materials and Proteins [J]. Progress in Chemistry, 2019, 31(2/3): 236-244.
[2] Bingjie Zhang, Qian S. Liu, Qunfang Zhou, Jianqing Zhang, Guibin Jiang. Neurotoxicological Effects of Nanosilver [J]. Progress in Chemistry, 2018, 30(9): 1392-1402.
[3] Wang Yunhai,Luo Yunjing**,Zhong Rugang . Protein Damage Induced by Peroxynitrite [J]. Progress in Chemistry, 2007, 19(06): 893-901.