Maternal exposure to air pollutant PM2.5 induces autistic-like behavior in adult offspring mice

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition with heterogeneous etiology. Individuals with ASD display core behavioral deficits, including impaired social communication and interaction skills, repetitive behavior, and intellectual disability with wide degrees of severity among individuals. Apart from hindering an individual’s physical and psychological development, ASD also adversely affects the daily life of individuals and their families. The prevalence rate of ASD has been reported to be in the range of 1%–2% according to numerous studies conducted in Asia, Europe, and North America, with a higher prevalence in males than in females (4:1).
Emerging studies have indicated the significant influence of environmental factors on increasing ASD susceptibility. It was recently reported that approximately 20% of 215 ASD candidate genes are epigenetic regulators, suggesting the importance of the interaction between genetic and environmental factors on the etiology of ASD. Gene and environment interactions are thought to contribute to the increased prevalence of ASD.
Among the environmental factors, the increase in air pollutants in our living environment is an emerging concern. Epidemiological studies have revealed that long-term prenatal or postnatal exposure to hazardous air pollutants is potentially linked to ASD. Ambient air pollutant particulate matter (PM), could adversely affect neurodevelopment. Prenatal and postnatal exposure to PM with sizes less than 2.5 µm (PM2.5) is significantly correlated with an increased risk of ASD, suggesting the potential role of PM2.5 exposure in increasing ASD susceptibility.
Maternal exercise has been suggested that a long-lasting improvement and transgenerational neuroplasticity could be induced by maternal exercise in human brains. In this project, I aim to investigate the potential effects of maternal exposure to PM2.5 on causing autism-like behaviors in offspring, and to examine whether maternal running could protect the offspring from developing autistic phenotypes. The results have revealed that maternal exposure to PM2.5 induced core ASD behavior, including impaired social recognition memory and increased repetitive behavior, as well as, impairment in hippocampal dependent learning and memory performance. Maternal running was able to reverse core ASD-like behavior including social recognition memory and repetitive behavior, but not learning and memory impairment. The results also showed that maternal exposure to PM2.5 impaired the dendritic development of immature neurons in the hippocampal dentate gyrus, but did not affect hippocampal neurogenesis and neuroinflammation. I hypothesize it may due to difference in maturation and integration into neural circuitry as indicated by the reduction in total dendritic length of immature neurons in offspring with maternal PM2.5 exposure. Other mechanisms including changes in oxidative stress, gene expression and gut microbiota profile could also play a role in underlying behavioral deficits as we observed in our model. The underlying mechanisms warrant further investigation.

Date of Award	30 Jan 2021
Original language	English
Awarding Institution	Department of Rehabilitation Sciences The Hong Kong Polytechnic University
Supervisor	Suk Yu Yau (Chief supervisor)