Perinatal Exposure to Diesel Exhaust-Origin Secondary Organic Aerosol Induces Autism-Like Behavior in Rats.

Tin-Tin Win-Shwe, Chaw Kyi-Tha-Thu, Yuji Fujitani, Shinji Tsukahara, Seishiro Hirano
Author Information
  1. Tin-Tin Win-Shwe: Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
  2. Chaw Kyi-Tha-Thu: Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama City 338-8570, Japan.
  3. Yuji Fujitani: Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan. ORCID
  4. Shinji Tsukahara: Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama City 338-8570, Japan.
  5. Seishiro Hirano: Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication, poor social interactions, and repetitive behaviors. We aimed to examine autism-like behaviors and related gene expressions in rats exposed to diesel exhaust (DE)-origin secondary organic aerosol (DE-SOA) perinatally. Sprague-Dawley pregnant rats were exposed to clean air (control), DE, and DE-SOA in the exposure chamber from gestational day 14 to postnatal day 21. Behavioral phenotypes of ASD were investigated in 10~13-week-old offspring using a three-chambered social behavior test, social dominance tube test, and marble burying test. Prefrontal cortex was collected to examine molecular analyses including neurological and immunological markers and glutamate concentration, using RT-PCR and ELISA methods. DE-SOA-exposed male and female rats showed poor sociability and social novelty preference, socially dominant behavior, and increased repetitive behavior. Serotonin receptor (5-HT(5B)) and brain-derived neurotrophic factor (BDNF) mRNAs were downregulated whereas interleukin 1 β (IL-β) and heme oxygenase 1 (HO-1) mRNAs were upregulated in the prefrontal cortex of male and female rats exposed to DE-SOA. Glutamate concentration was also increased significantly in DE-SOA-exposed male and female rats. Our results indicate that perinatal exposure to DE-SOA may induce autism-like behavior by modulating molecules such as neurological and immunological markers in rats.

Keywords

References

  1. J Neurodev Disord. 2009 Jun;1(2):133-40 [PMID: 21547712]
  2. Annu Rev Neurosci. 1990;13:171-82 [PMID: 1970230]
  3. Environ Res. 2015 Jul;140:414-20 [PMID: 25957837]
  4. Toxicol Appl Pharmacol. 2008 Jan 15;226(2):192-8 [PMID: 17950771]
  5. J Neurodev Disord. 2020 Dec 16;12(1):41 [PMID: 33327933]
  6. Environ Health Perspect. 2015 Mar;123(3):264-70 [PMID: 25522338]
  7. Part Fibre Toxicol. 2008 Mar 11;5:3 [PMID: 18331653]
  8. Dev Med Child Neurol. 2005 Aug;47(8):551-5 [PMID: 16108456]
  9. Neuroscience. 2020 Oct 1;445:31-41 [PMID: 31705895]
  10. Proc Natl Acad Sci U S A. 2016 Nov 8;113(45):E7097-E7105 [PMID: 27791080]
  11. Neurotoxicol Teratol. 2013 Mar-Apr;36:67-81 [PMID: 22918031]
  12. Mol Neurobiol. 2019 Apr;56(4):2741-2759 [PMID: 30056576]
  13. Am J Hum Genet. 2004 Mar;74(3):552-7 [PMID: 14963808]
  14. Toxicol Pathol. 2004 Nov-Dec;32(6):650-8 [PMID: 15513908]
  15. J Neuroimmunol. 1998 May 1;85(1):106-9 [PMID: 9627004]
  16. J Toxicol Sci. 2018;43(11):631-643 [PMID: 30404997]
  17. PLoS One. 2011 May 04;6(5):e19299 [PMID: 21573236]
  18. Am J Hum Genet. 2007 Dec;81(6):1289-97 [PMID: 17999366]
  19. Environ Pollut. 2020 Jan;256:113307 [PMID: 31733973]
  20. Transl Psychiatry. 2020 Jan 15;10(1):4 [PMID: 32066658]
  21. Am J Med Genet B Neuropsychiatr Genet. 2009 Apr 5;150B(3):421-4 [PMID: 18615476]
  22. Nature. 2010 Oct 14;467(7317):824-7 [PMID: 20944744]
  23. Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):3-18 [PMID: 12732219]
  24. Nanotoxicology. 2012 Aug;6(5):543-53 [PMID: 21663545]
  25. Environ Int. 2019 Dec;133(Pt A):105149 [PMID: 31629172]
  26. Front Neurosci. 2016 Jan 25;9:524 [PMID: 26834549]
  27. Neurotoxicology. 2017 Mar;59:140-154 [PMID: 26721665]
  28. Environ Health Perspect. 2014 Sep;122(9):939-45 [PMID: 24901756]
  29. Int J Environ Res Public Health. 2019 Jan 09;16(2): [PMID: 30634489]
  30. Inhal Toxicol. 2009 Feb;21(3):200-9 [PMID: 18991064]
  31. Neurotoxicology. 2008 Nov;29(6):940-7 [PMID: 18926851]
  32. Toxicol Lett. 2006 May 25;163(2):153-60 [PMID: 16293374]
  33. Environ Health Perspect. 2006 Aug;114(8):1172-8 [PMID: 16882521]
  34. Dialogues Clin Neurosci. 2012 Sep;14(3):281-92 [PMID: 23226953]
  35. Environ Health Perspect. 2012 Jul;120(7):a258-60 [PMID: 22543002]
  36. JAMA Psychiatry. 2013 Jan;70(1):71-7 [PMID: 23404082]
  37. Ann Neurol. 2005 Jan;57(1):67-81 [PMID: 15546155]
  38. Part Fibre Toxicol. 2020 Jan 29;17(1):8 [PMID: 31996222]
  39. Int J Environ Res Public Health. 2014 Oct 30;11(11):11286-307 [PMID: 25361045]
  40. Epidemiology. 2015 Jan;26(1):30-42 [PMID: 25286049]
  41. Curr Environ Health Rep. 2015 Dec;2(4):430-9 [PMID: 26399256]
  42. Nanomaterials (Basel). 2015 Jun 30;5(3):1147-1162 [PMID: 28347057]
  43. Neuropsychopharmacology. 2008 Jan;33(1):73-83 [PMID: 17882234]
  44. Nat Genet. 2003 May;34(1):27-9 [PMID: 12669065]
  45. Toxicol Appl Pharmacol. 2012 Aug 1;262(3):355-62 [PMID: 22659509]
  46. Biol Psychiatry. 2010 Aug 15;68(4):368-76 [PMID: 20674603]
  47. Environ Sci Technol. 2012 Jan 17;46(2):704-12 [PMID: 22191732]
  48. Inhal Toxicol. 2004 Jun;16(6-7):437-45 [PMID: 15204759]
  49. Pediatrics. 2011 Aug;128(2):344-55 [PMID: 21746727]
  50. J Autism Dev Disord. 2015 Apr;45(4):1062-9 [PMID: 25287899]
  51. Neurotoxicology. 2008 Jan;29(1):190-201 [PMID: 18031821]
  52. Int J Mol Sci. 2011;12(9):6267-80 [PMID: 22016657]
  53. Nat Genet. 2007 Jan;39(1):25-7 [PMID: 17173049]
  54. Pediatr Neurol. 1997 Jul;17(1):88-90 [PMID: 9308986]
  55. EMBO J. 2010 Jan 6;29(1):196-208 [PMID: 19893493]
  56. Indoor Air. 2012 Oct;22(5):415-26 [PMID: 22372506]
  57. Arch Pharm Res. 2010 Oct;33(10):1539-56 [PMID: 21052932]
  58. J Autism Dev Disord. 2010 Dec;40(12):1423-30 [PMID: 20414802]
  59. Inhal Toxicol. 2009 Aug;21(10):828-36 [PMID: 19653804]
  60. Curr Environ Health Rep. 2017 Jun;4(2):156-165 [PMID: 28417440]

Grants

  1. JP19K12361/Grant-in-Aid for Scientific Research (C) JSPS KAKENHI
  2. 1620AA041/a research fund from the National Institute for Environmental Studies, Japan

MeSH Term

Aerosols
Air Pollutants
Animals
Autism Spectrum Disorder
Brain-Derived Neurotrophic Factor
Female
Gene Expression Regulation
Heme Oxygenase-1
Humans
Interleukin-1beta
Male
Pregnancy
Prenatal Exposure Delayed Effects
Rats
Rats, Sprague-Dawley
Receptors, Serotonin
Vehicle Emissions

Chemicals

Aerosols
Air Pollutants
Bdnf protein, rat
Brain-Derived Neurotrophic Factor
Interleukin-1beta
Receptors, Serotonin
Vehicle Emissions
Heme Oxygenase-1

Word Cloud

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