Sleep disruption due to prenatal environmental toxin exposure and neurodevelopment disorder pathology

The prevalence of neurodevelopmental disorders (NDDs), such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), has increased rapidly over the past two decades. As such, much research has gone into the root causes and mechanisms of these disorders. Previous studies on the genetic roots of NDDs have identified several alleles associated with NDD pathology, however, prenatal environmental stressors and toxins are thought to contribute greatly to this recent increase.

Sleep plays a critical role in synapse remodeling, especially during adolescence. Astrocytes, a type of glial cell essential to regulating neuronal activity, have recently been shown to modulate the sleep-wake cycle. Specifically, astrocytes seem to regulate both depth and duration of NREM sleep. Previous work has shown that sleep appears to be particularly sensitive to environmental stressors and toxins. 

In the case of neurodevelopmental disorders, such as autism spectrum disorder, sleep disturbances are observed in nearly 86% of patients. Thus, the project I will be working on this summer aims to investigate the mechanisms by which prenatal exposure to environmental toxins impacts the development of neurodevelopmental disorder pathology. 

In my mentor’s previous work, she identified that a prenatal combined diesel exhaust particle and maternal stress (DEP/MS) paradigm results in neurodevelopmental disorder pathology in offspring. 

Using this mouse model, we plan to address two main questions. Firstly, how does prenatal exposure to maternal stress and environmental toxins impact sleep patterns in offspring? Secondly, do we observe changes in gene expression patterns and astrocyte physiology in the brains of these mice?

We’ve begun by using electroencephalography (EEG) and electromyography (EMG) to analyze sleep patterns in DEP/MS mice offspring. By doing this, we hope to determine how time spent in NREM and REM sleep differs between control and DEP/MS mice. We then plan to isolate RNA from frontal and parietal cortical astrocytes in order to analyze gene expression patterns through quantitative real-time PCR. Additionally, building on the sex differences in NDD pathology observed in my mentor’s previous work, we plan to use the forced-swim test to measure depressive behavior in DEP/MS mice.