MATERNAL EXPOSURE TO AIR POLLUTANT PM2.5 INDUCES AUTISTIC-LIKE BEHAVIOR IN OFFSPRING

Background

Autism spectrum disorder (ASD) is a devastating neurodevelopmental disorder with increasing prevalence worldwide 1. Existing evidence indicates that environmental factors (particularly in utero or during early life) can increase ASD risk 2,3. Recent meta-analysis and systemic review concluded that exposure to PM2.5 during pregnancy increases risk of ASD in newborns4.We hypothesize that maternal exposure to PM2.5 impairs hippocampal neuroplasticity to induce behavioral deficits that resembles autism-like behavior in the offspring. Aims : Determine whether maternal exposure to PM5 induces autism-like behaviors in mouse offspring, Determine whether maternal exposure to PM5 impairs hippocampal structural and synaptic plasticity in mouse offspring.

Method

Eight to ten-week old female C57 mice will be pair-housed and will be subjected to intratracheal instillation of PM2.5 with PM2.5 suspended in artificial lung fluid at the concentration of 3.5 µg/µl (PM2.5 group) or vehicle as control group. PM2.5 with 30 µl for each mouse, every 3 days will be administered to the female mice continuously for 15 days. After the pre-exposure, a breeder male mouse (6-8 week old) will be introduced to the holding cage for a week leaving them uninterrupted to reduce stress and increase fertility rate during mating period. Intratracheal instillation will then be resumed every three day continuously throughout gestation period. Both female and male offspring at the age of 5-6 week old will be subjected to behavioral tests, biochemical assays, electrophysiology experiments.

Results

Maternal exposure to PM2.5 induced core ASD behavior, including impaired social recognition memory, increased repetitive behavior, and impairment in hippocampal dependent learning and memory performance. The behavioral deficits are concurrent with impaired dendritic branching of immature neurons and long-term potentiation in the hippocampal dentate gyrus, though there were no significant effects on altering hippocampal adult neurogenesis and neuroinflammation.

Discussion & Conclusion

The results have suggested that chronic maternal exposure to PM2.5 could induce behavioral abnormalities in adult offspring, which could be linked to impaired neuroplasticity in the hippocampus.

References

Lyall, K., et al. The Changing Epidemiology of Autism Spectrum Disorders. Annual review of public health 38, 81-102 (2017). Gronborg, T.K., Schendel, D.E. &Parner, E.T. Recurrence of autism spectrum disorders in full- and half-siblings and trends over time: a population-based cohort study.

JAMA pediatrics 167, 947-953 (2013). Hallmayer, J., et al. Genetic heritability and shared environmental factors among twin pairs with autism. Archives of general psychiatry 68, 1095-1102 (2011). Dutheil, F., et al. Autism spectrum disorder and air pollution: A systematic review and meta analysis. Environ Pollut 278, 116856 (2021).