Role of SHANK3 in concentrated ambient PM2. 5 exposure induced autism-like phenotype

Kang Li; Xiaotian Liang; Xiaoqian Xie; Lei Tian; Jun Yan; Bencheng Lin; Huanliang Liu; Wenqin Lai; Xiaohua Liu; Zhuge Xi

doi:10.1016/j.heliyon.2023.e14328

Role of SHANK3 in concentrated ambient PM2. 5 exposure induced autism-like phenotype

Heliyon. 2023 Mar 6;9(3):e14328. doi: 10.1016/j.heliyon.2023.e14328. eCollection 2023 Mar.

Authors

Kang Li¹, Xiaotian Liang^{1

2}, Xiaoqian Xie^{1

2}, Lei Tian¹, Jun Yan¹, Bencheng Lin¹, Huanliang Liu¹, Wenqin Lai¹, Xiaohua Liu¹, Zhuge Xi^{1

2}

Affiliations

¹ Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China.
² Binzhou Medical College, Yantai, 264000, China.

Abstract

Perinatal air pollution plays an important role in the development of autism. However, research on the pathogenic mechanism remains limited. In this study, the model of systemic inhalation of concentrated approximately 8-fold the level (mean concentration was 224 μg/m³) reported in ambient outdoor air of PM2.5 (particulate matters that are 2.5 μm or less in diameter)in early-postnatal male Sprague-Dawley (SD) rats was established. Through a series of autism-related behavioral tests, it was identified that young rats (postnatal day 1-day21, named PND1-PND21) exposed to PM2.5 exhibited typical autistic phenotypes, such as impaired language communication, abnormal repetitive and stereotyped behaviors, and impaired social skills. Moreover, synaptic abnormalities have been found in the brain tissues of young rats exposed to PM2.5. In terms of the molecular mechanism, we found that the levels of SH3 and multiple ankyrin repeat domains 3 (SHANK3) expression and key molecular proteins in the downstream signaling pathways were decreased in the brain tissues of the exposed rats. Finally, at the epigenetic level, SHANK3 methylation levels were increased in young rats exposed to PM2.5. In conclusion, the study revealed that PM2.5 exposure might induce the early postnatal autism through the SHANK3 signaling pathway by affecting the SHANK3 methylation levels and reducing the SHANK3 expression levels. The study could provide new ideas for autism etiology and a theoretical basis for the prevention and treatment of autism in children.

Keywords: Autism; Behavioral tests; Brain; DNA methylation; PM2.5; SHANK3; Young rats.