Decreased Reelin Expression and Organophosphate Pesticide Exposure Alters Mouse Behavior and Brain Morphology.
Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders, including autism spectrum disorders.
In this study, we examined the combinatorial effect of two factors thought to be involved in autism – reduction in the expression of the extracellular matrix protein reelin and prenatal exposure to an organophosphate pesticide, chlorpyrifos oxon.
Mice with reduced reelin expression or prenatal exposure to chlorpyrifos oxon exhibited subtle changes in ultrasound vocalization, open field behavior, social interaction, and repetitive behavior.
Paradoxically, mice exposed to both variables often exhibited a mitigation of abnormal behaviors, rather than increased behavioral abnormalities as expected.
In addition, we identified specific differences in males and females in response to both of these variables.
In addition to behavioral abnormalities, we also identified anatomical alterations in the olfactory bulb, piriform cortex, hippocampus, and cerebellum.
As with our behavioral studies, anatomical alterations also appeared to be ameliorated in the presence of both variables. While these observations support an interaction between loss of reelin expression and chlorpyrifos oxon exposure, our results suggest a complexity to this interaction beyond an additive effect of individual phenotypes.