PMID- 28915388 OWN - NLM STAT- MEDLINE DCOM- 20180502 LR - 20190122 IS - 1873-4847 (Electronic) IS - 0955-2863 (Linking) VI - 49 DP - 2017 Nov TI - EPA and DHA, but not ALA, have antidepressant effects with 17beta-estradiol injection via regulation of a neurobiological system in ovariectomized rats. PG - 101-109 LID - S0955-2863(17)30043-8 [pii] LID - 10.1016/j.jnutbio.2017.07.012 [doi] AB - Our previous studies found that n-3 polyunsaturated fatty acids (PUFAs) and estrogen had synergistic antidepressant-like effects. The purpose of the present study was to investigate the hypothesis that three major n-3 PUFAs, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), individually had antidepressant effects combined with 17beta-estradiol-3-benzoate (E) through a neurobiological pathway in ovariectomized rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0% n-3 PUFAs and 1% ALA, EPA and DHA relative to total energy intake for 12 weeks and were injected with corn oil or E every 4 days during the last 3 weeks. Supplementation of EPA, DHA and E increased serum concentrations of serotonin and climbing behavior, and decreased immobility during a forced swimming test. Supplementation with EPA, DHA and E also decreased hippocampal expressions of interleukin-6 and tumor necrosis factor-alpha, and increased cAMP response element binding protein, brain-derived neurotrophic factor (BDNF) and estrogen receptor-alpha. Immunofluorescence staining consistently showed elevated expressions of BDNF. Magnetic resonance spectroscopy showed that E increased glucose and decreased glutamate, glutamine and myo-inositol concentrations regardless of n-3 PUFA supplementation. In addition, supplementation with EPA, DHA and E decreased levels of nitrite and nitrate. However, ALA had no antidepressant effect. The present study suggested that the antidepressant-like effects of EPA and DHA supplementation and E injection could be due to the regulation of serotonergic neurotransmission and inflammatory cytokines rather than due to the antioxidative system. Supplementation with n-3 PUFA and E had the additional function of modulating neurometabolites in the hippocampus. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Choi, Jeong-Eun AU - Choi JE AD - Department of Food and Nutrition, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. FAU - Park, Yongsoon AU - Park Y AD - Department of Food and Nutrition, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. Electronic address: yongsoon@hanyang.ac.kr. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170805 PL - United States TA - J Nutr Biochem JT - The Journal of nutritional biochemistry JID - 9010081 RN - 0 (Antidepressive Agents) RN - 0 (Nerve Tissue Proteins) RN - 0RBV727H71 (alpha-Linolenic Acid) RN - 1S4CJB5ZGN (estradiol 3-benzoate) RN - 25167-62-8 (Docosahexaenoic Acids) RN - 333DO1RDJY (Serotonin) RN - 4TI98Z838E (Estradiol) RN - AAN7QOV9EA (Eicosapentaenoic Acid) SB - IM MH - Animals MH - Antidepressive Agents/*therapeutic use MH - Behavior, Animal/drug effects MH - Brain Chemistry/drug effects MH - Depression/immunology/metabolism/pathology/*prevention & control MH - *Dietary Supplements MH - *Disease Models, Animal MH - Docosahexaenoic Acids/*therapeutic use MH - Eicosapentaenoic Acid/*therapeutic use MH - Estradiol/administration & dosage/analogs & derivatives/*therapeutic use MH - Female MH - Hippocampus/drug effects/immunology/metabolism/pathology MH - Hormone Replacement Therapy MH - Injections, Subcutaneous MH - Nerve Tissue Proteins/metabolism MH - Ovariectomy/adverse effects MH - Random Allocation MH - Rats, Wistar MH - Serotonergic Neurons/drug effects/immunology/metabolism/pathology MH - Serotonin/blood MH - alpha-Linolenic Acid/therapeutic use OTO - NOTNLM OT - Antioxidant OT - BDNF OT - Depression OT - Estrogen OT - N-3 polyunsaturated fatty acids OT - Neurometabolites OT - Rats EDAT- 2017/09/16 06:00 MHDA- 2018/05/03 06:00 CRDT- 2017/09/16 06:00 PHST- 2017/01/13 00:00 [received] PHST- 2017/06/28 00:00 [revised] PHST- 2017/07/19 00:00 [accepted] PHST- 2017/09/16 06:00 [pubmed] PHST- 2018/05/03 06:00 [medline] PHST- 2017/09/16 06:00 [entrez] AID - S0955-2863(17)30043-8 [pii] AID - 10.1016/j.jnutbio.2017.07.012 [doi] PST - ppublish SO - J Nutr Biochem. 2017 Nov;49:101-109. doi: 10.1016/j.jnutbio.2017.07.012. Epub 2017 Aug 5.