Table 1.
Experimental design and results summary of animal studies in references.
| References | Year | Animals | Experimental model | Omega-3 Dose | Effects | Molecular change |
|---|---|---|---|---|---|---|
| Song et al. (95) | 2009 | Sprague Dawley rats | Olfactory bulb resection depression model | 1% EPA diet | Water maze: spatial memory↑ | mRNA expression and activity of cPLA2↓; Serum IL-1β and PGE2 concentrations↓; CRF mRNA expression and blood corticosterone concentration↓; NGF expression in the hippocampus↑; |
| Ferraz et al. (102) | 2011 | Wistar rats | Restraint stress induced depression model | 3.0 g/kg animal weight of an oral compound containing 12% of EPA and 18% of DHA | FST: immobility frequency↓; swimming frequency↑; climbing frequency↑; Water maze test: mean latency time↓; percentage of spent time in target quadrant↑; percentage of entries into closed arms↓; EPM: percentage of entries into open arms↑; percentage of time spent in closed arms↓; percentage of time spent in the open arms↑ | None |
| Labrousse et al. (204) | 2012 | C57Bl6/J mice | Control diet non-depression model | An isocaloric LCω3 PUFA supplemented diet containing a mixture of rapeseed oil, high-oleic sunflower oil, palm oil and tuna oil resulting in a 10% EPA and 7% DHA diet | Spatial recognition: Spatial memory deficit↓ | AA/dGLA↑; EPA and DHA in the brain↑; (dGLA+EPA)/AA↑; microglia-dependent activation↓; proinflammatory cytokines production in microglia↓; CD11b mRNA expression↓; TNF-α expression mRNA↓; IL-6 mRNA expression↓; IL-1β expression↓; length of astrocytic processes in aged mice↑; c-Fos positive cells↑; microglia-dependent activation↓; proinflammatory cytokines production↓ |
| Balvers et al. (193) | 2012 | C57BL/6 mice | i.p. LPS induced depression model | 1% or 3% fish oil | None | DHEA↑; EPEA↑; endocannabinoids↓; NAEs↓; DGLEA↓; adipose tissue levels of SEA↑; plasma levels of SEA↓; ARA↓; DHA↑; EPA↑; oxylipins↓; LTB4 in ileum and adipose tissue↓; LTB4 in liver↑; Lipoxin A4↑ |
| Larrieu et al. (205) | 2014 | C57BL/6 mice | Chronic social defeat stress induced depression model | 3.1% lipids | Number of social explorations↓ OFT: time spent exploring the center↓ | Simplification of apical dendritic tree on pyramidal neurons of the dlPFC and dmPFC↓; total corticosterone elevation↓; HPA axis hyperactivity↓; neuronal atrophy↓ |
| Wu et al. (92) | 2016 | Sprague Dawley rats | Depressive model induced by intraperitoneal injection of doxorubicin | EPA: DHA 3:2; EPA 510mg/kg; DHA 360mg/kg | Weight loss↓ OFT:Number of crossings↑; number of rearing↑; latency time↓; FST: swimming time↑; immobility time↓ | MDA in prefrontal cortex↓; MDA in hippocampus↓; SOD in hippocampus↑; IL-1 mRNA expression in prefrontal cortex↓; IL-6 mRNA expression in prefrontal cortex↓; IL-6 mRNA expression in hippocampus↓; TNF-α mRNA expression in hippocampus↓; protein level of NF-κB↓; protein level of iNOS↓; Number of nuclear pyknosis↓; Apoptotic index TUNEL-positive cells↓gene expression of Bcl-xl↑; gene expression of Bcl-2↓. |
| Larrieu et al. (103) | 2016 | C57BL6/J mice | Mifepristone subcutaneous implantation non-depression model | Containing 6% of rapeseed oil | Number of social interaction↑; OFT: Center time ↑ | Plasma corticosterone levels ↓; the total apical dendritic material in both dlPFC and dmPFC ↑ |
| Abdel-Maksoud et al. (153) | 2016 | Sprague-Dawley rats | Control diet non-depression model | EPA: DHA 3:2; EPA 180mg; DHA120mg | None | BDNF gene expression↑; serum total cholesterol↓; triacylglycerol↓; serum glucose level↓; HOMA index↓; triacylglycerol levels↓ |
| Morgese et al. (98) | 2017 | Wistar rats | Control diet non-depression model | Containing 6% total fat in the form of only rapeseed oil (n-3 enriched, rich in linolenic acid 18:3n-3) | FST: immobility frequency↓; swimming frequency↑; struggling frequency↑; OFT: time of performing self-grooming↓ | Cortical 5-HT concentrations↓; CRF content↑; corticosterone levels↑; plasmatic Aβ levels ↑; NA↑ |
| Tang et al. (104) | 2018 | Sprague-Dawley rats | Control diet non-depression model | Fish oil (20 g/ kg) | FST: immobility frequency↓; SPT: sucrose preference↑ | Protein expressions of glucocorticoid receptor ↑ |
| Cigliano et al. (206) | 2019 | MRL/lpr mice | Non-depression model | An oral dose (30 mg) of FO (85%) containing 16 and 9,5 mg of DHA and EPA | None | Double-stranded DNA (anti-dsDNA) IgGs↓; TNF-α↓; PPAR-γ↑; DHA concentration in the brain↑; BDNF↑; SynaptophysinI↑; SynaptotagminI↑; SynapsinI↑; compensatory hyperactivation of phase 2 enzymes (GSR, G6PD) activities↓; GCL↓; GSR mRNA levels↓; Nrf2 ↓ |
| Yang et al. (183) | 2019 | Sprague-Dawley rats | CUMS induced depression model | Fish oil (20 g/kg) | FST: Immobility times↓; SPT: sucrose preference↑; OFT: number of locomotor crossing↑; number of rearing↑ | 5-HIAA↓; DOPAC↑; HVA↓; VMA↓; GLN↑; DA turnover rate 2↓; NE turnover rate 1↓; NE turnover rate 2↓; DA/NE between-metabolite ratio 1↑ |
| Choi et al. (107) | 2020 | Wistar rats | Pup separation-induced depression model | EPA:DHA 5:3; EPA 450mg; DHA260mg | FST: immobility time↓; climbing time↑; Sucrose preference index↑; Pup retrieval test: Latency of the first contact↓; Latency to retrieve↓ | Adrenocorticotropic hormone↓; corticosterone↓; hypothalamic corticotrophin releasing factor↓; hippocampal miRNA-218↓; prostaglandin E2↓; TNF-α↓; IL-6↓; miRNA-155↑; serotonin↑; serotonin-1A receptor↑; cAMP response element binding protein (CREB)↑; pCREB; brain-derived neurotrophic factor↑; miRNA-182↑. |
| Cutuli et al. (144) | 2020 | C57BL/6 mice | icv. mu-p75-saporin induced depression model | EPA: DHA 5:4 300 mg/kg | EPM: expected aversion↓; NORT: total object contact time↓ | Preserved hippocampal volume; neurogenesis in the dentate gyrus↑;astrogliosis in the hippocampus↓ |
| Peng et al. (207) | 2020 | Sprague Dawley rats | CUMS induced depression model | 1% ethyl-EPA (96% pure) or 1% DHA (96% pure) | SPT: Sucrose consumption↑; FST: immobility time↓; OFT: numbers of locomotor crossing↑; numbers of rearing↑ | Arachidonic acid (AA) level in the brain↓; docosapentaenoic acid in the brain↑; total cholesterol level ↓; serum corticosterone ↓; NE ↑; 5-HT ↑; NE/MHPG↑; IL-1β↓; IL-6↓; TNF-α↓; CD11b expression↓; p75NTR expression↓; GDNF expression↑; NF-KB and p38 expression↓; bax expression↓; bcl-2↑; bax/bcl-2↓ |
| Carabelli et al. (185) | 2020 | Wistar rats | i.p. LPS induced depression model | 3.0 g/kg (approximately 3.0 mL/kg) of fish oil containing 18% of EPA and 12% of DHA | Weight loss↓; FST: swimming frequency↑; immobility time↓ | 5-HT↑; 5HIAA/5-HT↓; IDO expression↓ |
| Choi et al. (110) | 2021 | Wistar rats | CMS+ovariectomy induced depression model | EPA: DHA 3:2; EPA 300mg/kg; DHA260mg/kg | FST: swimming time↑; immobility time↓; SPT: sucrose preference index↑ | Brain endocannabinoid/oxylipin levels↑; blood levels of adrenocorticotropic hormone and corticosterone↓; tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and prostaglandin E2↓; brainstem serotonin levels and hippocampal expression of the serotonin-1A receptor, cAMP response element-binding protein (CREB), phospho-CREB, and brain-derived neurotrophic factor↑ |
“↑” Indicates increased levels or protein expression of factor substances in vivo after treatment with omega-3 compared to controls. “↓” Indicates decreased levels or protein expression of factor substances in vivo after treatment with omega-3 compared to controls. FST, Forced Swimming Test; SPT, Sucrose Preference Test; OFT, Open Field Test; EPM, Elevated Plus Maze; NORT, New Object Recognize Test; NGF, Nerve growth factor; LTB4, Leukotriene B4; MDA, Malondialdehyde; HOMA index, Homeostatic model assessment index; HVA, Homovanillic acid; VMA, Vanillylmandelic acid; GLN, glutamine.