Skip to main content
SpringerLink
Log in

Impact of diesel particulate matter on the olfactory bulb of mice: insights from behavioral, histological, and molecular assessments

  • Original Article
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Background

Diesel particulate matter (DPM) constitutes a significant air pollutant that adversely affects neurological health through the olfactory pathway. Although extensive human epidemiological and animal research exists, the specific mechanisms underlying DPM-induced olfactory dysfunction have not been definitively elucidated.

Objective

This study aimed to conduct a comprehensive analysis of the behavioral, histological, and molecular changes in the olfactory bulb (OB) of mice following intranasal exposure to 10 mg/kg DPM for a duration of four weeks.

Results

Exposure to DPM led to notable olfactory impairment in the mice, characterized by an elevation in Iba-1-positive microglia, though without inducing neuronal cell death. Transcriptomic evaluation revealed 84 differentially expressed genes (DEGs) in the OB that met the criteria of fold change greater than 1.5 and a p value less than 0.05. Within this set, 55 genes were upregulated and 29 were downregulated. Gene ontology-based functional analysis revealed that these DEGs were primarily related to sensory organ morphogenesis, energy homeostasis, and the regulation of monocyte aggregation. Subsequent investigation using the Kyoto Encyclopedia of Genes and Genomes database identified enriched pathways connected to neuroactive ligand-receptor interactions and calcium signaling.

Conclusion

Our findings suggest a plausible association between DPM-induced olfactory dysfunction and disruptions in a range of molecular pathways. This hypothesis is supported by observed alterations in gene expression and the presence of mild neuroinflammation, primarily driven by microglial activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BP:

Biological processes

Bmp15 :

Bone morphogenetic protein 15

cDNA:

Complementary DNA

CC:

Cellular component

CON:

Control

DEGs:

Differentially expressed genes

DPM:

Diesel particulate matter

FPKM:

Fragments per kilobase of transcript per million mapped reads

GO:

Gene ontology

H&E:

Hematoxylin–eosin

Iba-1:

Ionized calcium-binding adapter molecule 1

KEGG:

Kyoto Encyclopedia of Genes and Genomes

Mas1 :

Mas1 proto-oncogene, G protein-coupled receptor

MF:

Molecular function

NeuN:

Neuronal nuclei

NF-κB:

Nuclear factor kappa B

OB:

Olfactory bulb

PBS:

Phosphate-buffered saline

PBS-T:

PBS containing 0.1% tween 20

PFA:

Paraformaldehyde

PPI:

Protein–protein interaction

RAS:

Renin-angiotensin system

RNA-seq:

RNA-sequencing

RT-qPCR:

Reverse transcription-quantitative real-time polymerase chain reaction

STRING:

Search Tool for the retrieval of interacting genes/proteins

Tnfsf13b :

Tumor necrosis factor superfamily member 13b

References

  • Ahn JH et al (2016) Long-term observation of neuronal degeneration and microgliosis in the gerbil dentate gyrus after transient cerebral ischemia. J Neurol Sci 363:21–26

    Article  CAS  PubMed  Google Scholar 

  • Ang MJ et al (2020) Transcriptome profiling reveals novel candidate genes related to hippocampal dysfunction in SREBP-1c knockout mice. Int J Mol Sci 23:4131

    Article  Google Scholar 

  • Balasubramanian N, James TD, Selvakumar GP, Reinhardt J, Marcinkiewcz CA (2023) Repeated ethanol exposure and withdrawal alters angiotensin-converting enzyme 2 expression in discrete brain regions: implications for SARS-CoV-2 neuroinvasion. Alcohol Clin Exp Res (Hoboken) 47:219–239

    Article  CAS  PubMed  Google Scholar 

  • Blum JL, Chen LC, Zelikoff JT (2017) Exposure to ambient particulate matter during specific gestational periods produces adverse obstetric consequences in mice. Environ Health Perspect 125:077020

    Article  PubMed  PubMed Central  Google Scholar 

  • Bos I et al (2012) Changed gene expression in brains of mice exposed to traffic in a highway tunnel. Inhal Toxicol 24:676–686

    Article  CAS  PubMed  Google Scholar 

  • Brann JH, Firestein SJ (2014) A lifetime of neurogenesis in the olfactory system. Front Neurosci 8:182

    Article  PubMed  PubMed Central  Google Scholar 

  • Brook RD et al (2010) Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 121:2331–2378

    Article  CAS  PubMed  Google Scholar 

  • Calderon-Garciduenas L et al (2002) Air pollution and brain damage. Toxicol Pathol 30:373–389

    Article  CAS  PubMed  Google Scholar 

  • Chen Z et al (2021) Glial activation and inflammation in the NTS in a rat model after exposure to diesel exhaust particles. Environ Toxicol Pharmacol 83:103584

    Article  CAS  PubMed  Google Scholar 

  • Chung DW et al (2010) Systemic administration of lipopolysaccharide induces cyclooxygenase-2 immunoreactivity in endothelium and increases microglia in the mouse hippocampus. Cell Mol Neurobiol 30:531–541

    Article  CAS  PubMed  Google Scholar 

  • Daiber A et al (2020) Effects of air pollution particles (ultrafine and fine particulate matter) on mitochondrial function and oxidative stress—implications for cardiovascular and neurodegenerative diseases. Arch Biochem Biophys 696:108662

    Article  CAS  PubMed  Google Scholar 

  • Ehsanifar M et al (2021) Hippocampal inflammation and oxidative stress following exposure to diesel exhaust nanoparticles in male and female mice. Neurochem Int 145:104989

    Article  CAS  PubMed  Google Scholar 

  • Fukuda S, Taga T (2006) Roles of BMP in the development of the central nervous system. Clin Calcium 16:781–785

    CAS  PubMed  Google Scholar 

  • Ge SX, Jung D, Yao R (2020) ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics 36:2628–2629

    Article  CAS  PubMed  Google Scholar 

  • Genc S, Zadeoglulari Z, Fuss SH, Genc K (2012) The adverse effects of air pollution on the nervous system. J Toxicol 2012:782462

    Article  PubMed  PubMed Central  Google Scholar 

  • Gu G et al (2023) Ang-(1–7)/MasR axis promotes functional recovery after spinal cord injury by regulating microglia/macrophage polarization. Cell Biosci 13:23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hajbabaei M, Johnson KC, Guthrie J, Durbin TD (2013) Assessment of the emissions from the use of California Air Resources Board qualified diesel fuels in comparison with Federal diesel fuels. Int J Engine Res 14:138–150

    Article  CAS  Google Scholar 

  • Hoffmann B et al (2009) Chronic residential exposure to particulate matter air pollution and systemic inflammatory markers. Environ Health Perspect 117:1302–1308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann BR et al (2017) Mechanisms of Mas1 receptor-mediated signaling in the vascular endothelium. Arterioscler Thromb Vasc Biol 37:433–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hong S, Weerasinghe-Mudiyanselage PDE, Kang S, Moon C, Shin T (2023) Retinal transcriptome profiling identifies novel candidate genes associated with visual impairment in a mouse model of multiple sclerosis. Anim Cells Syst (seoul) 27:219–233

    Article  CAS  PubMed  Google Scholar 

  • Huang JS et al (2022) Immature olfactory sensory neurons provide behaviourally relevant sensory input to the olfactory bulb. Nat Commun 13:6194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jensen GS, Leon-Palmer NE, Townsend KL (2021) Bone morphogenetic proteins (BMPs) in the central regulation of energy balance and adult neural plasticity. Metabolism 123:154837

    Article  CAS  PubMed  Google Scholar 

  • Jeong SY, Kim J, Park EK, Baek MC, Bae JS (2020) Inhibitory functions of maslinic acid on particulate matter-induced lung injury through TLR4-mTOR-autophagy pathways. Environ Res 183:109230

    Article  CAS  PubMed  Google Scholar 

  • Ji X et al (2022) Olfactory bulb microglia activation mediated neuronal death in real-ambient particulate matter exposure mice with depression-like behaviors. Sci Total Environ 821:153456

    Article  CAS  PubMed  Google Scholar 

  • Juaid N et al (2021) Anti-hepatocellular carcinoma biomolecules: molecular targets insights. Int J Mol Sci 22:10774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim J et al (2019) Gene Expression profile of olfactory transduction signaling in an animal model of human multiple sclerosis. Exp Neurobiol 28:74–84

    Article  PubMed  PubMed Central  Google Scholar 

  • LaFever BJ, Imamura F (2022) Effects of nasal inflammation on the olfactory bulb. J Neuroinflammation 19:294

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee J et al (2023) Particulate matter exposure and neurodegenerative diseases: a comprehensive update on toxicity and mechanisms. Ecotoxicol Environ Saf 266:115565

    Article  CAS  PubMed  Google Scholar 

  • Li N, Xia T, Nel AE (2008) The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med 44:1689–1699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li P et al (2014) Association between individual PM2.5 exposure and DNA damage in traffic policemen. J Occup Environ Med 56:e98–e101

    Article  CAS  PubMed  Google Scholar 

  • Liu X et al (2023) Traumatic brain injury-induced inflammatory changes in the olfactory bulb disrupt neuronal networks leading to olfactory dysfunction. Brain Behav Immun 114:22–45

    Article  CAS  PubMed  Google Scholar 

  • Lv H et al (2021) TAK-242 ameliorates olfactory dysfunction in a mouse model of allergic rhinitis by inhibiting neuroinflammation in the olfactory bulb. Int Immunopharmacol 92:107368

    Article  CAS  PubMed  Google Scholar 

  • Ma Z et al (2023) TMEM59 ablation leads to loss of olfactory sensory neurons and impairs olfactory functions via interaction with inflammation. Brain Behav Immun 111:151–168

    Article  CAS  PubMed  Google Scholar 

  • Machado CF, Reis-Silva TM, Lyra CS, Felicio LF, Malnic B (2018) Buried food-seeking test for the assessment of olfactory detection in mice. Bio Protoc 8:e2897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morris RH, Counsell SJ, McGonnell IM, Thornton C (2021) Early life exposure to air pollution impacts neuronal and glial cell function leading to impaired neurodevelopment. BioEssays 43:e2000288

    Article  PubMed  Google Scholar 

  • Nelson DR et al (2022) Molecular mechanisms behind safranal’s toxicity to HepG2 cells from dual omics. Antioxidants (Basel) 11:1125

    Article  CAS  PubMed  Google Scholar 

  • Peixoto MS, de Oliveira Galvao MF, Batistuzzo de Medeiros SR (2017) Cell death pathways of particulate matter toxicity. Chemosphere 188:32–48

    Article  CAS  PubMed  Google Scholar 

  • Roberts A, Trapnell C, Donaghey J, Rinn JL, Pachter L (2011) Improving RNA-Seq expression estimates by correcting for fragment bias. Genome Biol 12:R22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song SJ, Park B, Jo K, Kim CS (2021) Damage to olfactory organs of adult zebrafish induced by diesel particulate matter. Int J Mol Sci 23:407

    Article  PubMed  PubMed Central  Google Scholar 

  • Urist MR (1965) Bone: formation by autoinduction. Science 150:893–899

    Article  CAS  PubMed  Google Scholar 

  • van Eeden SF, Hogg JC (2002) Systemic inflammatory response induced by particulate matter air pollution: the importance of bone-marrow stimulation. J Toxicol Environ Health A 65:1597–1613

    Article  PubMed  Google Scholar 

  • Wada M et al (2021) Behavioral characterization in MPTP/p mouse model of Parkinson’s disease. J Integr Neurosci 20:307–320

    Article  PubMed  Google Scholar 

  • Wang H et al (2017) The acute airway inflammation induced by PM(2.5) exposure and the treatment of essential oils in Balb/c mice. Sci Rep 7:44256

    Article  PubMed  PubMed Central  Google Scholar 

  • Weerasinghe-Mudiyanselage PDE, Ang MJ, Kang S, Kim JS, Moon C (2022) Structural plasticity of the hippocampus in neurodegenerative diseases. Int J Mol Sci 23:3349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Werder EJ, Shrestha S, O'Brien KM, Chen H, Sandler DP (2021) Traffic-related air pollution and olfactory impairment among women in a nationwide US cohort. In: ISEE Conference Abstracts

  • Win-Shwe TT, Yamamoto S, Fujitani Y, Hirano S, Fujimaki H (2008) Spatial learning and memory function-related gene expression in the hippocampus of mouse exposed to nanoparticle-rich diesel exhaust. Neurotoxicology 29:940–947

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This work was supported by a grant from the National Research Foundation (NRF) of Korea funded by the Korean Government (NRF-2020R1A4A1019395; NRF-2022R1A2C100402212).

Author information

Author notes

  1. Jeongmin Lee and Poornima D. E. Weerasinghe-Mudiyanselage have equally contributed to this study.

Authors and Affiliations

  1. Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, Republic of Korea

    Jeongmin Lee, Poornima D. E. Weerasinghe-Mudiyanselage, Bohye Kim, Sohi Kang, Joong-Sun Kim & Changjong Moon

Authors
  1. Jeongmin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Poornima D. E. Weerasinghe-Mudiyanselage
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bohye Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sohi Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joong-Sun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Changjong Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JL and CM designed the research plan. JL, PDEW-M, BK, SK, J-SK, and CM performed the experiments and analyzed the data. JL, PDEW-M, and CM wrote the manuscript.

Corresponding author

Correspondence to Changjong Moon.

Ethics declarations

Conflict of interest

Jeongmin Lee: declares no conflict of interest. Poornima D.E. Weerasinghe-Mudiyanselage: declares no conflict of interest. Bohye Kim: declares no conflict of interest. Sohi Kang: declares no conflict of interest. Joong-Sun Kim: declares no conflict of interest. Changjong Moon: declares no conflict of interest.

Ethical approval

All the mice experimental protocols were approved by the Animal Care and Use Committee of Chonnam university, all animals were treated according to the guidelines for animal experimentation of Chonnam university in Gwangju, Republic of Korea (8 November 2022; CNU IACUC-YB-2022–136).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 482 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, J., Weerasinghe-Mudiyanselage, P.D.E., Kim, B. et al. Impact of diesel particulate matter on the olfactory bulb of mice: insights from behavioral, histological, and molecular assessments. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00414-6

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13273-023-00414-6

Keywords

Search

Navigation