Sakayori Nobuyuki, Tokuda Hisanori, Yoshizaki Kaichi, Kawashima Hiroshi, Innis Sheila M, Shibata Hiroshi, Osumi Noriko
Department of Developmental Neuroscience, Center for Neuroscience, United Centers for Advanced Research and Translational Medicine, Tohoku University School of Medicine.
Tohoku J Exp Med. 2016 Sep;240(1):31-7. doi: 10.1620/tjem.240.31.
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.
ω-6（n-6）和ω-3（n-3）多不饱和脂肪酸（PUFAs）是正常大脑发育所必需的营养素。主要的膳食n-6和n-3多不饱和脂肪酸分别是亚油酸（LA）和α-亚麻酸（ALA）。我们之前已经表明，母体饮食中这些多不饱和脂肪酸之间的失衡，即富含LA而缺乏ALA，会影响大脑发育并增加小鼠后代与焦虑相关的行为。在这里，我们进一步探讨了暴露于母体LA:ALA失衡的后代在与焦虑相关行为上的性别差异。我们给怀孕小鼠喂食LA过量/ALA缺乏（LA(ex)/ALA(def)）的饮食，并从早期哺乳期开始就用均衡的LA:ALA饮食饲养它们的后代。当后代成年后，对它们进行行为和生化分析。我们发现，与暴露于对照饮食的后代相比，暴露于LA(ex)/ALA(def)饮食的雄性和雌性后代都表现出与焦虑相关的行为增加，而这种情况在两性之间的观察结果有所不同。雌性后代还因母体摄入LA(ex)/ALA(def)饮食而表现出多动。另一方面，两性均未检测到异常的抑郁行为。我们还发现，无论母体饮食或后代性别如何，大脑中n-6与n-3多不饱和脂肪酸的比例均未受影响。由于已知n-6/n-3比例会影响情绪行为，因此可以合理地假设，大脑发育期间暴露的LA:ALA失衡是导致成年期焦虑增强的关键。本研究表明，母体饮食中LA和ALA之间的失衡会以性别依赖的方式增加后代与焦虑相关行为。
