title: Fish oil supplementation attenuates neuroinflammation and alleviates depressive-like behavior in rats submitted to repeated lipopolysaccharide.
abstract: OBJECTIVE
  Depression is frequently associated with inflammation, whereas omega-3 polyunsaturated fatty acids (PUFAs) primarily found in fish oil possess anti-inflammatory properties. Although converging studies suggest an antidepressant effect of PUFAs, there is limited evidence directly linking the neuro-immune modulating features of PUFAs to the antidepressant actions.
  
  
  METHODS
  Therefore, we assessed the effects of fish oil (FO) supplementation on behavioral changes, inflammatory cytokine expression and oxidative reactions in frontal cortex and hippocampus of rats following repeated peripheral immune challenge by lipopolysaccharide (LPS) for 2 weeks (500 μg/kg every other day).
  
  
  RESULTS
  Repeated LPS administration induced the rats to a depressive-like state and increased mRNA expression of pro-inflammatory cytokines, including 1L-1β, 1L-6 and TNF-α, in frontal cortex and hippocampus. FO supplementation attenuated the LPS-induced abnormal behavior and brain inflammatory response. Concurrent with the antidepressant action, FO also reduced LPS-induced oxidative reactions and neural apoptosis in the rat brain, as evidenced by decreased malondialdehyde (MDA) production, increased catalase activities and inhibited pro-apoptotic protein Bax mRNA expression. In addition, FO inhibited activation of NF-κB and iNOS induced by LPS. Interestingly, we found FO suppressed the activation of the inflammasome NLRP3 and ionotropic purinergic receptor P2X7R evoked by LPS, suggesting a potential anti-inflammatory mechanism for PUFAs. Besides, FO also restored the LPS-induced neurochemical disturbance, especially the balance between serotonin and kynurenine branches of tryptophan metabolism, which is tightly associated with depression.
  
  
  CONCLUSIONS
  These findings provide novel insights into the antidepressant action of PUFAs and further strengthen the link between inflammation and depression.
authors.affiliation: Institute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, 272000, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Dang
authors.affiliation: Department of Cardiology, Jining First People's Hospital, Jining Medical University, Jining, 272000, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors.forename: Mimi
authors.initials: M
authors.lastname: Tang
authors.affiliation: Institute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, 272000, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Institute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, 272000, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Gong
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Hongxiao
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Institute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, 272000, China. jiangpeicsu@sina.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003863:Depression / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D019587:Dietary Supplements / Q000009:adverse effects; D005395:Fish Oils / Q000009:adverse effects / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020078:Neurogenic Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use; D017397:Prefrontal Cortex / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D015415:Biomarkers; D016207:Cytokines; D005395:Fish Oils; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C573346:Nlrp3 protein, rat; C546470:P2rx7 protein, rat; D058486:Receptors, Purinergic P2X7
keywords: Depression; Lipopolysaccharide; Neuroinflammation; Neurotransmitters; P2X7R; ω-3 Polyunsaturated fatty acids