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

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

NOBUYUKI SAKAYORI,^1,2 HISANORI TOKUDA,³ KAICHI YOSHIZAKI,¹ HIROSHI KAWASHIMA,³ SHEILA M. INNIS,⁴ HIROSHI SHIBATA³ and NORIKO OSUMI¹

¹Department of Developmental Neuroscience, Center for Neuroscience, United Centers for Advanced Research and Translational Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan
²Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan
³Institute for Health Care Science, Suntory Wellness Ltd., Soraku-gun, Kyoto, Japan
⁴Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada

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.

keywords —— anxiety; emotional development; omega-3; omega-6; sex difference

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Tohoku J. Exp. Med., 2016, 240, 31-37

Correspondence: Noriko Osumi, Ph.D., Department of Developmental Neuroscience, Center for Neuroscience, United Centers for Advanced Research and Translational Medicine, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.

e-mail: osumi@med.tohoku.ac.jp