Maternal methyl donor supplementation regulates the effects of cafeteria diet on behavioral changes and nutritional status in male offspring.

Abstract

Nutritional status and maternal feeding during the perinatal and postnatal periods can program the offspring to develop long-term health alterations. Epidemiologic studies have demonstrated an association between maternal obesity and intellectual disability/cognitive deficits like autism spectrum disorders (ASDs) in offspring. Experimental findings have consistently been indicating that maternal supplementation with methyl donors, attenuated the social alterations and repetitive behavior in offspring. This study aims to analyze the effect of maternal cafeteria diet and methyl donor-supplemented diets on social, anxiety-like, and repetitive behavior in male offspring, besides evaluating weight gain and food intake in both dams and male offspring. C57BL/6 female mice were randomized into four dietary formulas: control Chow (CT), cafeteria (CAF), control + methyl donor (CT+M), and cafeteria + methyl donor (CAF+M) during the pre-gestational, gestational, and lactation period. Behavioral phenotyping in the offspring was performed by 2-month-old using Three-Chamber Test, Open Field Test, and Marble Burying Test. We found that offspring prenatally exposed to CAF diet displayed less social interaction index when compared with subjects exposed to Chow diet (CT group). Notably, offspring exposed to CAF+M diet recovered social interaction when compared to the CAF group. These findings suggest that maternal CAF diet is efficient in promoting reduced social interaction in murine models. In our study, we hypothesized that a maternal methyl donor supplementation could improve the behavioral alterations expected in maternal CAF diet offspring. The CAF diet also contributed to a social deficit and anxiety-like behavior in the offspring. On the other hand, a maternal methyl donor-supplemented CAF diet normalized the social interaction in the offspring although it led to an increase in anxiety-like behaviors. These findings suggest that a methyl donor supplementation could protect against aberrant social behavior probably targeting key genes related to neurotransmitter pathways.