Discussion
Together, our findings support the gene-environment interaction hypothesis of ASD by showing that different genetic and environmental risk factors could act synergistically to exacerbate behavioral changes. In addition, by showing the independent effects of each risk factor, our findings suggest that ASD phenotypes could be caused by different underlying mechanisms.
Methods
In this study, we tested the interaction between these two risk factors by exposing Wildtype, Cntnap2+/- , and Cntnap2 -/- rats to Polyinosinic: Polycytidylic acid (Poly I:C) MIA at gestation day 9.5.
Results
Our findings showed that Cntnap2 deficiency and Poly I:C MIA independently and synergistically altered ASD-related behaviors like open field exploration, social behavior, and sensory processing as measured through reactivity, sensitization, and pre-pulse inhibition (PPI) of the acoustic startle response. In support of the double-hit hypothesis, Poly I:C MIA acted synergistically with the Cntnap2 -/- genotype to decrease PPI in adolescent offspring. In addition, Poly I:C MIA also interacted with the Cntnap2+/- genotype to produce subtle changes in locomotor hyperactivity and social behavior. On the other hand, Cntnap2 knockout and Poly I:C MIA showed independent effects on acoustic startle reactivity and sensitization.