Early Postnatal Exposure to Ultrafine Particulate Matter Air Pollution: Persistent Ventriculomegaly, Neurochemical Disruption, and Glial Activation Preferentially in Male Mice
Open accessAbstract
Background: Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression. Objectives: We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development. Methods: We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4–7 and 10–13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified. Results: We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males. Conclusions: We observed brain region– and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be mechanistically related to observations linking ambient air pollutant exposure and adverse neurological/neurodevelopmental outcomes in humans. Citation: Allen JL, Liu X, Pelkowski S, Palmer B, Conrad K, Oberdörster G, Weston D, Mayer-Pröschel M, Cory-Slechta DA. 2014. Early postnatal exposure to ultrafine particulate matter air pollution: persistent ventriculomegaly, neurochemical disruption, and glial activation preferentially in male mice. Environ Health Perspect 122:939–945; http://dx.doi.org/10.1289/ehp.1307984
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Early postnatal PM0.1 exposure led to ventriculomegaly preferentially in male mice that persisted through young adulthood.
“Allen et al. [57] verified early postnatal PM0.1 exposure led to ventriculomegaly, i.e., lateral ventricle dilation, preferentially in male mice that persisted through young adulthood.”
From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [57]
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Cites
Oxidative Pathways for Catecholamines in the Genesis of Neuromelanin and Cytotoxic Quinones
GRAHAM, D. G. (1978) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)13535-9 · Cited by 1,126 · see citing works
Extrapolating brain development from experimental species to humans
Clancy, B., Finlay, B. L., Darlington, R. B., & Anand, K. J. S. (2007) · NeuroToxicology · doi:10.1016/j.neuro.2007.01.014 · Cited by 812 · see citing works
Traffic-Related Air Pollution, Particulate Matter, and Autism
Volk, H. E., Lurmann, F., Penfold, B., Hertz-Picciotto, I., & McConnell, R. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.266 · Cited by 638 · see citing works
Ambient Air Pollution and Autism in Los Angeles County, California
Becerra, T. A., Wilhelm, M., Olsen, J., Cockburn, M., & Ritz, B. (2013) · Environmental Health Perspectives · doi:10.1289/ehp.1205827 · Cited by 355 · see citing works
Residential Proximity to Freeways and Autism in the CHARGE Study
Volk, H. E., Hertz-Picciotto, I., Delwiche, L., Lurmann, F., & McConnell, R. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.1002835 · Cited by 347 · see citing works
Barttfeld, P., Wicker, B., Cukier, S., Navarta, S., Lew, S., & Sigman, M. (2011) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2010.11.024 · Cited by 311 · see citing works
The global burden of conduct disorder and attention-deficit/hyperactivity disorder in 2010
Erskine, H. E., Ferrari, A. J., Polanczyk, G. V., Moffitt, T. E., Murray, C. J. L., Vos, T., Whiteford, H. A., & Scott, J. G. (2014) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12186 · Cited by 207 · see citing works
Flagged first, then by citations
Research works printed but not linked: 52
- Allen JL Conrad K Oberdörster G Johnston CJ Sleezer B Cory-Slechta DA 2013 Developmental exposure to concentrated ambient particles and preference for immediate reward in mice. Environ Health Perspect 121 32 38; 10.1289/ehp.1205505 23063827 PMC3553438 · DOI · Paper page
- Allen JL Liu X Weston D Conrad K Oberdörster G Cory-Slechta DA 2014a Consequences of developmental exposure to concentrated ambient ultrafine particle air pollution combined with the adult paraquat and maneb model of the Parkinson’s disease phenotype in male mice. Neurotoxicology 41 80 88 24486957 PMC3978140
- Allen JL Liu X Weston D Prince L Oberdörster G Finkelstein JN 2014b Developmental exposure to concentrated ambient ultrafine particulate matter air pollution in mice results in persistent and sex-dependent behavioral neurotoxicity and glial activation. Toxicol Sci 140 160 178 24690596 PMC4081635
- Balschun D Wetzel W Del Rey A Pitossi F Schneider H Zuschratter W 2004 Interleukin-6: a cytokine to forget. FASEB J 18 1788 1790 15345694
- Benes BM Berretta S 2001 GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25 1 27 11377916
- Benes FM Kwok EW Vincent SL Todtenkopf MS 1998 A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. Biol Psychiatry 44 88 97 9646890
- Bigler ED 1987 The clinical significance of cortical atrophy and ventricular enlargement in schizophrenia. Arch Clin Neuropsychol 2 4 385 392 14589704
- Block ML Calderón-Garcidueñas L 2009 Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci 32 506 516 19716187 PMC2743793
- Boyle CA Boulet S Schieve LA Cohen RA Blumberg SJ Yeargin-Allsopp M 2011 Trends in the prevalence of developmental disabilities in US children, 1997–2008. Pediatrics 6 1034 1042 21606152
- Cao RY St Amand T Li X Yoon SH Wang CP Song H 2012 Prostaglandin receptor EP4 in abdominal aortic aneurysms. Am J Pathol 181 1 313 321 22595380
- Centers for Disease Control and Prevention. 2007 Prevalence of autism spectrum disorders—autism and developmental disabilities monitoring network. MMWR Surveill Summ 68 1 11 17287714
- Cohen G 1983 The pathobiology of Parkinson’s disease: biochemical aspects of dopamine neuron senescence. J Neural Transm Suppl 19 89 103 6321651
- Cook EH 1990 Autism: review of neurochemical investigation. Synapse 6 292 308 1700486
- Cory-Slechta DA Virgolini MB Thiruchelvam M. Weston DD Bauter MR 2004 Maternal stress modulates the effects of developmental lead exposure. Environ Health Perspect 112 717 730; 10.1289/ehp.6481 15121516 PMC1241967 · DOI
- Cory-Slechta DA Weston D Liu S Allen JL 2013 Brain hemispheric differences in the neurochemical effects of lead, prenatal stress, and the combination and their amelioration by behavioral experience. Toxicol Sci 132 2 419 430 23358193 PMC3693514
- Deverman BE Patterson PH 2009 Cytokines and CNS development. Neuron 64 61 78 19840550
- Fannon D Tennakoon L Sumich A O’Ceallaigh S Doku V Chitnis X 2000 Third ventricle enlargement and developmental delay in first-episode psychosis: preliminary findings. Br J Psychiatry 177 354 359 11116778
- Fogal B Hewett SJ 2008 Interleukin-1β: a bridge between inflammation and excitotoxicity? J Neurochem 106 1 23 18315560
- Gilmore JH Smith LC Wolfe HM Hertzberg BS Smith JK Chescheir NC 2008 Prenatal mild ventriculomegaly predicts abnormal development of the neonatal brain. Biol Psychiatry 64 12 1069 1076 18835482 PMC2630424
- Gilmore JH van Tol J Kliewer MA Silva SG Cohen SB Hertzberg BS 1998 Mild ventriculomegaly detected in utero with ultrasound: clinical associations and implications for schizophrenia. Schizophr Res 33 133 140 9789905
- Gilmore JH van Tol JJ Lewis Streicher H Williamson K Cohen SB Greenwood RS 2001 Outcome in children with fetal mild ventriculomegaly: a case series. Schizophr Res 48 2–3 219 226 11295375
- Goshen I Yirmiya R 2009 Interleukin-1 (IL-1): a central regulator of stress responses. Front Neuroendocrinol 30 30 45 19017533
- Grace AA 2012 Dopamine system dysregulation by the hippocampus: implications for the pathophysiology and treatment of schizophrenia. Neuropharmacology 62 1342 1348 21621548 PMC3179528
- Griffiths PD Reeves MJ Morris JE Mason G Russell SA Paley MN 2010 A prospective study of fetuses with isolated ventriculomegaly investigated by antenatal sonography and in utero MR imaging. AJNR AM J Neuroradiol 31 1 106 111 19762458 PMC7964094
- Hastings TG 1995 Enzymatic oxidation of dopmaine: the role of prostaglandin H synthase. J Neurochem 64 2 919 924 7830086
- James HE 1992 Hydrocephalus in infancy and childhood. Am Fam Physician 45 733 742 1739057
- Kirkbride JB Errazuriz A Croudace TJ Morgan C Jackson D Boydell J 2012 Incidence of schizophrenia and other psychoses in England, 1950–2009: a systematic review and meta-analyses. PLoS One 7 3 e31660; 10.1371/journal.pone.0031660 22457710 PMC3310436 · DOI
- Kuban K Sanocka U Leviton A Allred EN Pagano M Dammann O 1999 White matter disorders of prematurity: association with intraventricular hemorrhage and ventriculomegaly. The Developmental Epidemiology Network. J Pediatr 134 5 539 546 10228286
- Kyriakopoulou V Vatansever D Elkommos S Dawson S McGuinness A Allsop J 2014 Cortical overgrowth in fetuses with isolated ventriculomegaly. Cereb Cortex 24 8 2141 2150 23508710
- Laskin MD Kingdom J Toi A Chitayat D Ohlsson A 2005 Perinatal and neurodevelopmental outcome with isolated fetal ventriculomegaly: a systematic review. J Matern Fetal Neonatal Med 18 5 289 298 16390787
- Lim YH Kim H Kim JH Bae S Park HY Hong YC 2012 Air pollution and symptoms of depression in elderly adults. Environ Health Perspect 120 1023 1028; 10.1289/ehp.1104100 22514209 PMC3404652 · DOI
- Lisabeth LD Escobar JD Dvonch JT Sanchez BN Majersik JJ Brown DL 2008 Ambient air pollution and risk for ischemic stroke and transient ischemic attack. Ann Neurol 64 53 59 18508356 PMC2788298
- Mandell JG Neuberger T Drapaca CS Webb AG Schiff SJ 2010 The dynamics of brain and cerebrospinal fluid growth in normal versus hydrocephalic mice. J Neurosurg Pediatr 6 1 10 20593980
- Manfredi R Tognolini A Bruno C Raffaelli R Franchi M Pozzi Mucelli R 2010 Agenesis of the corpus callosum in fetuses with mild ventriculomegaly: role of MR imaging. Radiol Med 115 2 301 312 20017009
- Movsas TZ Pinto-Martin JA Whitaker AH Feldman JF Lorenz JM Korzeniewski SJ 2013 Autism spectrum disorder is associated with ventricular enlargement in a low birth weight population. J Pediatr 163 1 73 78 23410601 PMC4122247
- Pedersen CB Raaschou-Nielsen O Hertel O Mortensen PB 2004 Air pollution from traffic and schizophrenia risk. Schizophr Res 66 83 85 14693358
- Power MC Weisskopf MG Alexeeff SE Coull BA Spiro A III Schwartz J 2011 Traffic-related air pollution and cognitive function in a cohort of older men. Environ Health Perspect 119 682 687; 10.1289/ehp.1002767 21172758 PMC3094421 · DOI
- Sanfilipo M Lafargue T Arena L Rusinek H Kushner K Lautin A 2000 Fine volumetric analysis of the cerebral ventricular system in schizophrenia: further evidence for multifocal mild to moderate enlargement. Schizophr Bull 26 1 201 216 10755682
- Schneider H Pitossi F Balschun D Wagner A del Rey A Besedovsky HO 1998 A neuromodulatory role of interleukin-1β in the hippocampus. Proc Natl Acad Sci USA 95 7778 7783 9636227 PMC22755
- Schulz JB Lindenau J Seyfried J Dichgans J 2000 Glutathione, oxdiative stress and neurodegeneration. Eur J Biochem 267 4904 4911 10931172
- Schulz SC Koller MM Kishore PR Hamer RM Gehl JJ Friedel RO 1983 Ventricular enlargement in teenage patients with schizophrenia spectrum disorder. Am J Psychiatry 140 12 1592 1595 6650689
- Schwarz JM Sholar PW Bilbo SD 2012 Sex differences in microglial colonization of the developing rat brain. J Neurochem 120 948 963 22182318 PMC3296888
- Segman RH Meltzer A Gross-Tsur V Kosov A Frisch A Inbar E 2002 Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder. Mol Psychiatry 7 72 74 11803448
- Siddique S Banerjee M Ray MR Lahiri T 2011 Attention-deficit hyperactivity disorder in children chronically exposed to high level of vehicular pollution. Eur J Pediatr 7 923 929 21191614
- Tatli B Ozer I Ekici B Kalelioglu I Has R Eraslan E 2012 Neurodevelopmental outcome of 31 patients with borderline fetal ventriculomegaly. Clin Neurol Neurosurg 114 969 971 22405543
- Virgolini MB Rossi-George A Lisek R Weston DD Thiruchelvam M Cory-Slechta DA 2008 CNS effects of developmental Pb exposure are enhanced by combined maternal and offspring stress. Neurotoxicology 29 812 827 18440644 PMC2575115
- Volpe JJ 2001 Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res 50 5 553 562 11641446
- Volpe JJ 2003 Cerebral white matter injury of the premature infant—more common than you think. Pediatrics 112 1 Pt 1 176 180 12837883
- Volpe JJ 2005 Encephalopathy of prematurity includes neuronal abnormalities. Pediatrics 116 1 221 225 15995055
- Wellenius GA Burger MR Coull BA Schwartz J Suh HH Koutrakis P 2012 Ambient air pollution and the risk of acute ischemic stroke. Arch Intern Med 172 229 234 22332153 PMC3639313
- Weuve J Puett RC Schwartz J Yanosky JD Laden F Grodstein F 2012 Exposure to particulate air pollution and cognitive decline in older women. Arch Intern Med 172 219 227 22332151 PMC3622279
- Wright IC Rabe-Hesketh S Woodruff PW David AS Murray RM Bullmore ET 2000 Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 157 1 16 25 10618008
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“[57] C57BL/ 6J mice Ultrafine PM, concentrated ambient particles 96 μg/m(3) Inhalation PND4–7 and PND10–13 (with a group of males getting additional exposure on PND270) Ventriculomegaly in males that persisted through young adulthood; males also showed a decrease in CNS cytokines (whereas females showed an increase);…”
MethodAllen, J. L., Oberdorster, G., Morris-Schaffer, K., Wong, C., Klocke, C., Sobolewski, M., Conrad, K., Mayer-Proschel, M., & Cory-Slechta, D. A. (2017) · NeuroToxicology · doi:10.1016/j.neuro.2015.12.014 · Cited by 241 · see citing works
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Self-citationPrenatal and early-life diesel exhaust exposure causes autism-like behavioral changes in mice
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- Authors
- Allen, J. L., Liu, X., Pelkowski, S., Palmer, B., Conrad, K., Oberdörster, G., Weston, D., Mayer-Pröschel, M., & Cory-Slechta, D. A.
- Affiliations
- Department of Environmental Medicine, and
- Department of Biomedical Genetics, University of Rochester School of Medicine, Rochester, New York, USA
- ORCID
- Liu, Xiufang
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-06-05
- Volume
- 122
- Issue
- 9
- Pages
- 939-945
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC4154219
- OpenAlex
- W2085153618
- Cited by
- 186
- References
- 7
- Citations by year
- 2026: 14 · 2025: 10 · 2024: 20 · 2023: 10 · 2022: 23 · 2021: 14 · 2020: 17 · 2019: 23 · 2018: 15 · 2017: 17 · 2016: 12 · 2015: 10 · 2014: 1
- FWCI
- 8.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 1303 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institute of Environmental Health Sciences (ES-001247, K12ES019852, ES019105, R21ES019105, ES019852, P30ES001247, T32ES007026)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Indoor Air Quality and Microbial Exposure
- Keywords
- ultrafine particles, air pollution, ventriculomegaly, lateral ventricle dilation, sex differences, neuroinflammation, glial activation, neurotransmitters, glutamate, hippocampus, brain development, autism spectrum disorder, schizophrenia, postnatal exposure, mice
- MeSH terms
- Air Pollutants, Air Pollution, Animals, Brain, Female, Hydrocephalus, Male, Mice, Inbred C57BL, Neuroglia, Particle Size, Sex Factors, Cytokines, Neurotransmitter Agents, Mice, Particulate Matter
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