J. Lipid Res.  Neurobiology of Lipids (ISSN1683-5506)
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Journal of Lipid Research, Vol. 42, 1655-1663, October 2001
Copyright © 2001 by Lipid Research, Inc.


Original Article

Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat: level of n-6 fatty acids as another critical factor

Atsushi Ikemotoa, Masayo Ohishia, Yosuke Satoa, Noriaki Hatab, Yoshihisa Misawab, Yoichi Fujiia, and Harumi Okuyamaa
a Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori, Mizuhoku, Nagoya 467-8603, Japan
b Applied Research Department, Harima Chemicals, Tsukuba, Ibaraki 300-26, Japan

Correspondence to: Harumi Okuyama, To whom correspondence should be addressed., okuyamah{at}phar.nagoya-cu.ac.jp (E-mail)

Rats fed a semipurified diet supplemented with 3% (w/w) safflower oil [Saf, n-3 fatty acid deficient, high linoleic acid (18:2n-6)] through two generations exhibit decreased correct response ratios in a brightness-discrimination learning test compared with rats fed 3% perilla oil [Per, high {alpha}-linolenic acid (18:3n-3)]. This is associated with a decreased DHA (22:6n-3)-to-arachidonic acid (20:4n-6) ratio in brain lipids. In the first set of experiments, dietary oil was shifted from Saf to a mixture of 2.4% safflower oil plus 0.6% DHA after weaning (Saf-DHA), but all parameters measured in the learning test were essentially unchanged. Brain 22:6n-3 content of the Saf-DHA group reached that of the Per group but the levels of 20:4n-6 and docosatetraenoic acid (22:4n-6) did not decrease to those of the Per group at the start of the test. In the second set of experiments, dietary oil was shifted to a mixture of 0.6% safflower oil plus 1.2% oleic acid (OA) plus 1.2% DHA (Saf-OA-DHA group) with 18:2n-6 content comparable to that of the Per group. The Saf-OA-DHA group exhibited a learning performance similar to that of the Per group; brain 22:6n-3, 20:4n-6, and 22:4n-6 contents were also comparable to those of the Per group.

These results indicate that the altered learning behavior associated with a long-term n-3 fatty acid deficiency is reversed by supplementing 22:6n-3 after weaning, when the levels of competing n-6 fatty acids in the diet and brain lipids are limited. — Ikemoto, A., M. Ohishi, Y. Sato, N. Hata, Y. Misawa, Y. Fujii, and H. Okuyama. Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat: level of n-6 fatty acids as another critical factor. J. Lipid Res. 2001. 42: 1655–1663.

Supplementary key words: arachidonic acid, brain, docosahexaenoic acid, learning ability, linoleic acid, {alpha}-linolenic acid


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