Maternal Nutritional Imbalance between Linoleic Acid and Alpha-Linolenic Acid Increases Offspring’s Anxious Behavior with a Sex-Dependent Manner in Mice.

Key Findings

These authors have shown that maternal consumption of a LA^ex/ALA^def diet caused abnormal brain development and increased anxiety-related behavior in the mouse offspring. In this study, maternal LA:ALA imbalance induced different emotional consequences between the male and female offspring. Female offspring exposed to the control diet show fewer entries into the center zone than the male offspring exposed to the control diet. Due to this behavioral difference between the sexes, the impact of maternal LA:ALA imbalance on the number of entry into the center zone might be ineffective in the female offspring. This study shows increased anxiety-related behavior without abnormal depressive behavior in mice. Maternal LA:ALA imbalance during the prenatal and early postnatal stages may cause anxiety-related behavior in the offspring, while depression may be induced by maternal PUFA imbalance at later stages.  Maternal LA:ALA imbalance also induced hyperlocomotion in female offspring mice. The results show important roles for n-3 ALA on various behaviors as well as for anxiety disorders.

Abstract

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients for normal brain development. The principal dietary n-6 and n-3 PUFAs are linoleic acid (LA) and α-linolenic acid (ALA), respectively, We have previously shown that maternal dietary imbalance between these PUFAs, i.e., rich in LA and poor in ALA, affected brain development and increased anxiety-related behavior in the mouse offspring. Here we further addressed sex difference in anxiety-related behavior in the offspring exposed to maternal LA:ALA imbalance. We fed pregnant mice a LA excess/ALA deficient (LA(ex)/ALA(def)) diet, and raised their offspring on a well-balanced LA:ALA diet from an early lactation period. When the offspring were grown to adulthood, they were subjected to behavioral and biochemical analyses. We found that both male and female offspring exposed to the LA(ex)/ALA(def) diet showed increased anxiety-related behavior compared to those exposed to the control diet, which was differently observed between the sexes. The female offspring also exhibited hyperactivity by maternal intake of the LA(ex)/ALA(def) diet. On the other hand, abnormal depressive behavior was undetected in both sexes. We also found that the ratio of n-6 to n-3 PUFAs in the brain was unaffected regardless of maternal diet or offspring’s sex. Since the n-6/n-3 ratio is known to influence emotional behavior, it is reasonable to assume that LA:ALA imbalance exposed during brain development is the key for causing enhanced anxiety in adulthood. The present study indicates that maternal dietary imbalance between LA and ALA increases offspring’s anxiety-related behavior with a sex-dependent manner.