title: N-3 polyunsaturated fatty acids and 17β-estradiol injection induce antidepressant-like effects through regulation of serotonergic neurotransmission in ovariectomized rats.
abstract: Previous studies have suggested that estrogen and n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antidepressant-like effects. The purpose of the present study was to determine the interaction between n-3 PUFAs and estrogen, and their neurotrophic mechanism in rats after the forced swimming test (FST). Rats were fed a modified American Institute of Nutrition 93G diet with 0%, 1% or 2% EPA+DHA relative to the total energy intake during 12 weeks. At 8 weeks, rats were ovariectomized and injected with either 17β-estradiol-3-benzoate (E2) or corn oil during the last 3 weeks. Both n-3 PUFA supplementation and E2 injection increased climbing and decreased immobility during the FST. Serum serotonin concentration was also increased by both n-3 PUFA and E2. N-3 PUFA and E2 decreased hippocampal expressions of interleukin (IL)-6 and tumor necrosis factor-α, and increased cAMP response element binding protein (CREB), phosphorylated CREB and brain-derived neurotrophic factor (BDNF). N-3 PUFA supplementation decreased hippocampal expression of IL-1β only in rats injected with E2. Both n-3 PUFA supplementation and E2 injection increased estrogen receptor (ER)-α in the hippocampus, but ER-β was increased only by E2 injection. Additionally, there was a significant interaction between n-3 PUFA supplementation and E2 injection on the hippocampal expression of pCREB, suggesting membrane-mediated interaction of n-3 PUFAs and E2. In conclusion, both n-3 PUFA and E2 had antidepressant-like effects by regulating serotonergic neurotransmission through BDNF and inflammatory cytokines.
authors.affiliation: Department of Food and Nutrition, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-791, Korea.
authors.forename: Youri
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Food and Nutrition, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-791, Korea. Electronic address: yongsoon@hanyang.ac.kr.
authors.forename: Yongsoon
authors.initials: Y
authors.lastname: Park
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D003863:Depression / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D018565:Food-Drug Interactions; D007279:Injections, Subcutaneous; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010052:Ovariectomy / Q000009:adverse effects; D011897:Random Allocation; D017208:Rats, Wistar; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012701:Serotonin / Q000097:blood
chemical_list: D000928:Antidepressive Agents; D004967:Estrogens; D015525:Fatty Acids, Omega-3; D009419:Nerve Tissue Proteins; C074283:estradiol 3-benzoate; D012701:Serotonin; D004958:Estradiol
keywords: 17β-Estradiol-3-benzoate; BDNF; Forced swimming test; Inflammatory cytokines; N-3 polyunsaturated fatty acids; Rats