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© 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1‐nitropyrene (1‐NP), a key component of motor vehicle exhaust, on autism‐like behaviors in a mouse model. Three‐chamber test finds that prenatal 1‐NP exposure causes autism‐like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1‐NP‐exposed weaning pups. Immunofluorescence finds that prenatal 1‐NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1‐NP exposure retards tangential migration of GAD67‐positive interneurons and downregulates interneuron migration‐related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1‐NP exposure reduces hydroxymethylation of interneuron migration‐related genes through inhibiting ten‐eleven translocation (TET) activity in fetal forebrain. Supplement with alpha‐ketoglutarate (α‐KG), a cofactor of TET enzyme, reverses 1‐NP‐induced hypohydroxymethylation at specific sites of interneuron migration‐related genes. Moreover, α‐KG supplement alleviates 1‐NP‐induced migration retardation of interneurons in fetal forebrain. Finally, maternal α‐KG supplement improves 1‐NP‐induced autism‐like behaviors in weaning offspring. In conclusion, prenatal 1‐NP exposure causes autism‐like behavior partially by altering DNA hydroxymethylation of interneuron migration‐related genes in developing brain.

Details

Title
Prenatal 1‐Nitropyrene Exposure Causes Autism‐Like Behavior Partially by Altering DNA Hydroxymethylation in Developing Brain
Author
Zhao, Ting 1 ; Huang, Cheng‐Qing 2 ; Zhang, Yi‐Hao 1 ; Zhu, Yan‐Yan 1 ; Chen, Xiao‐Xi 1 ; Wang, Tao 3 ; Shao, Jing 3 ; Meng, Xiu‐Hong 3 ; Huang, Yichao 1 ; Wang, Hua 1 ; Wang, Hui‐Li 2 ; Wang, Bo 1 ; Xu, De‐Xiang 1   VIAFID ORCID Logo 

 Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China, Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China 
 School of Food and Bioengineering, Hefei University of Technology, Hefei, China 
 Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China 
Section
Research Article
Publication year
2024
Publication date
Jul 1, 2024
Publisher
John Wiley & Sons, Inc.
e-ISSN
21983844
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3083836924
Copyright
© 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.