Effect of Maternal Omega-6 Rich Diets and Prenatal Stress On Autistic-Like Sociability Deficits in Mice

Background: Multiple studies have reported prenatal stress as a potential risk factor for the development of autism spectrum disorder (ASD). In rodents, a significant reduction in sociability is seen in prenatally stressed offspring of genetically stress-susceptible dams.  Certain dietary factors that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in adult offspring. Adults with a diet rich in omega-6 polyunsaturated fatty acids (PUFAs) display increased stress reactivity.

Objectives: In our study, we wished to examine the effects of prenatal diet and prenatal stress on social behavior in the adult offspring in mice.  

Methods: Pregnant C57BL/6J dams were placed into a chronic variable stress group or a control group, and were also placed into a control diet or a diet rich in omega-6 PUFAs, in a 2 x 2 design. Mice placed in the chronic variable stress group were given one stressor per day beginning on gestational day 6 until the birth of the offspring. We subsequently tested the adult offspring (N = 86) beginning on postnatal day 60 for sociability, anxiety, and locomotor functioning using a 3-chambered social approach task, an elevated-plus maze, an open field task and a rotarod task.

Results: We found no differences between groups in the open field and the rotarod tasks (p > 0.05).  We did find a main effect of diet in the elevated-plus maze, with offspring whose mothers were exposed to a high-omega-6 PUFA diet during gestation showing increased anxiety levels (p = 0.038).  Additionally, these offspring displayed decreased levels of sociability in the 3-chamber social approach task, as they did not spend significantly more time with a stranger mouse than a novel object (p = 0.65), whereas mice exposed to the control diet during gestation did spend significantly more time with a stranger mouse than a novel object (p < 0.001).  No main effects of prenatal stress were observed, and no interaction between diet and stress was observed.

Conclusions: Our findings indicate that a maternal diet rich in omega-6 PUFAs during produce changes in sociability consistent with those observed in ASD. This provides evidence for a possible environmental risk factor that contributes to the production of autistic-like behavior in mice.  Exploration of the relationship between prenatal diet and ASD in humans will be necessary to determine the role of this finding in clinical ASD, and further investigation into the mechanism of action of this effect is warranted.